No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Chronic Urticaria is Usually Associated with Fibromyalgia Syndrome
Abstract
Although the pathophysiology of chronic urticaria is not fully understood, it is possible that dysfunctioning of peripheral cutaneous nerve fibres may be involved. It has also been suggested that fibromyalgia syndrome, a multi-symptomatic chronic pain condition, may be associated with alterations and dysfunctioning of peripheral cutaneous nerve fibres. The aim of this study was to determine whether patients with chronic urticaria are also affected by fibromyalgia syndrome. A total of 126 patients with chronic urticaria were investigated for fibromyalgia syndrome. An unexpectedly high proportion (over 70%) had fibromyalgia syndrome. The corresponding proportion for 50 control dermatological patients was 16%, which is higher than previously published data for the Italian general population (2.2%). It is possible that dysfunctional cutaneous nerve fibres of patients with fibromyalgia syndrome may release neuropeptides, which, in turn, may induce dermal microvessel dilatation and plasma extravasation. Furthermore, some neuropeptides may favour mast cell degranulation, which stimulates nerve endings, thus providing positive feedback. Chronic urticaria may thus be viewed in many patients, as a consequence of fibromyalgia syndrome; in fact, skin neuropathy (fibromyalgia syndrome) may trigger neurogenic skin inflammation (chronic urticaria).
... Although its pathogenesis is not well understood yet, there is evidence that peripheral nerves are implicated in its pathophysiology, and several neuropeptides have been found to be enhanced in CU (5). There is a network that communicates between cutaneous sensory nerves and immune skin cells; when these neuropeptides are released, they will act on the target cells producing erythema, oedema, hyperthermia and pruritus (6). Mast cells, one of the primary effector cells in the pathogenesis and development of urticaria, are located in the upper dermis, where wheal formation and sensory nerve stimulation occur (7). ...
... In this study, widespread pain was found to be more prevalent in the patients with CU than in the control group in a percentage of 60.9% and 11.6% respectively, whereas the prevalence of FMS among patients with CU was found to be 34.1% which is comparable to a study done by Oktayoğlu et al. (2), who found FMS affected 32.5% of his study group. However, the prevalence rate of FMS in patients with CU in our study was lower than that in a study conducted by Torresani et al. (6) who found, a prevalence rate of FMS in CU was 70.6% and declared that, such a high proportion was unexpected. This high result may be related to the inclusion of patients with DM, thyroid dysfunctions, haematological abnormalities, autoimmune disorders, and other systemic diseases in their study. ...
... The high prevalence rate of FMS in patients with CU in this study may be explained by the common underlying pathogenesis that involves the implication of the peripheral nerves and different neurotransmitters in the pathogenesis of both CU and FMS; when these neuropeptides are released, they will act on the target cells producing erythema, oedema, hyperthermia and pruritus; nociceptive C-fibres respond to histamine resulting in the release of these neuropeptides, in addition to substance P and calcitonin gene -related peptide (CGRP) which are known to be increased in CU skin, and play an important role in the pathogenesis of both CU and FMS (5,6,(11)(12)(13)(14). Another explanation for the high prevalence of FMS in CU may be related to the role of mast cells in the pathogenesis of both disorders. ...
Background: Fibromyalgia syndrome (FMS) can coexist with many autoimmune, rheumatic and in-flammatory disorders. Chronic urticaria (CU) and FMS are different types of diseases but share many clinical and pathological features. This study aims to evaluate these features and to investigate whether patients with CU are also affected by FMS.
... Although its pathogenesis is not well understood yet, there is evidence that peripheral nerves are implicated in its pathophysiology, and several neuropeptides have been found to be enhanced in CU (5). There is a network that communicates between cutaneous sensory nerves and immune skin cells; when these neuropeptides are released, they will act on the target cells producing erythema, oedema, hyperthermia and pruritus (6). Mast cells, one of the primary effector cells in the pathogenesis and development of urticaria, are located in the upper dermis, where wheal formation and sensory nerve stimulation occur (7). ...
... In this study, widespread pain was found to be more prevalent in the patients with CU than in the control group in a percentage of 60.9% and 11.6% respectively, whereas the prevalence of FMS among patients with CU was found to be 34.1% which is comparable to a study done by Oktayoğlu et al. (2), who found FMS affected 32.5% of his study group. However, the prevalence rate of FMS in patients with CU in our study was lower than that in a study conducted by Torresani et al. (6) who found, a prevalence rate of FMS in CU was 70.6% and declared that, such a high proportion was unexpected. This high result may be related to the inclusion of patients with DM, thyroid dysfunctions, haematological abnormalities, autoimmune disorders, and other systemic diseases in their study. ...
... The high prevalence rate of FMS in patients with CU in this study may be explained by the common underlying pathogenesis that involves the implication of the peripheral nerves and different neurotransmitters in the pathogenesis of both CU and FMS; when these neuropeptides are released, they will act on the target cells producing erythema, oedema, hyperthermia and pruritus; nociceptive C-fibres respond to histamine resulting in the release of these neuropeptides, in addition to substance P and calcitonin gene -related peptide (CGRP) which are known to be increased in CU skin, and play an important role in the pathogenesis of both CU and FMS (5,6,(11)(12)(13)(14). Another explanation for the high prevalence of FMS in CU may be related to the role of mast cells in the pathogenesis of both disorders. ...
Background: Fibromyalgia syndrome (FMS) can coexist with many autoimmune, rheumatic and in-flammatory disorders. Chronic urticaria (CU) and FMS are different types of diseases but share many clinical and pathological features. This study aims to evaluate these features and to investigate whether patients with CU are also affected by FMS.
... FMS patofizyolojisi henüz tam olarak açıklığa kavuşmamış olup son zamanlarda FMS'de periferal sinirlerin rolünün geçmişte düşünülenden daha fazla olduğu kabul edilmektedir 8 . FMS'nin periferal kutanöz sinir liflerinin değişikliği veya disfonksiyonu ile ilişkili olabileceği düşünülmektedir 9 . FMS'li hastaların deri biyopsilerinde artmış nörojenik inflamasyonla uyumlu bulguların saptanmış olması FMS patogenezinde nörojenik inflamasyonun rol oynadığı görüşünü desteklemektedir 10 . ...
... Bu ortak noktadan hareketle oluşturulan bir başka hipoteze göre her iki hastalığın patogenezinde de otoimmünite suçlanmaktadır ve periferal kutanöz sinirlerdeki değişiklikler otoimmünite ile açıklanmaya çalışılmıştır 24 Torresani ve ark. kronik ürtiker dışı deri hastalığı olan kontrol grubunda da FMS'nin yüksek oranda bulunmasını; inflamatuvar deri hastalıklarının da nörojenik inflamasyonla ilişkili olabileceği hipotezine bağlamışlardır 9 . Bu iki çalışmada kontrol grubu olarak alınan kişilerin deri hastalıklarının birebir aynı olmaması ve özellikle inflamatuvar olan deri hastalıklarındaki olası nörojenik inflamasyonun FMS'ye eğilim yaratıyor olabilmesi, kontrol grubu FMS oranlarının birbiriyle uyumlu olmamasını açıklayabilir. ...
... Bu büyük farklılık Torresani ve ark. tarafından yapılan çalışmada FMS'nin %70,6 gibi yüksek bir oranda saptanmış olmasıyla ilişkili olabilir 9 . Sonuç Çalışmadan elde ettiğimiz bulgular gösteriyor ki, kronik ürtikerli hastalarda FMS görülme sıklığı kontrol grubuna göre anlamlı olarak daha fazladır. ...
Background and Design: The aim of our study was to determine the frequency of fibromyalgia syndrome in chronic urticaria patients.
Materials and Methods: The study was carried out with the participation of 100 chronic urticaria patients and 61 control group patients. Chronic urticaria patients were investigated for the etiology of urticaria and the autologous serum skin test was performed in those patients. Both the chronic urticaria patients and the controls were evaluated for fibromyalgia syndrome, and the patients fulfilling the diagnostic criteria were diagnosed to have fibromyalgia syndrome.
Results: The frequency of fibromyalgia syndrome was significantly higher in chronic urticaria patients (23%), than in the control group (1.6%). All the patients, who were diagnosed with fibromyalgia syndrome, were female and the rate of female gender was significantly higher than in the group without fibromyalgia syndrome. Thyroid autoimmunity was positive in 26% of chronic urticaria patients. No significant difference was detected in the frequency of thyroid autoimmunity and autologous serum skin test positivity between the patients with and without fibromyalgia syndrome.
Conclusion: The prevalence of fibromyalgia syndrome in chronic urticaria patients is higher than in the general population. Therefore, we suggest evaluation of chronic urticaria patients in terms of fibromyalgia syndrome which is a disease that decreases the quality of life considerably. Furthermore, in order to treat these two diseases effectively, future studies are necessary to determine the common points in the pathogenesis.
... In the current study, the FMS incidence in CSU patients (26.4%) was significantly higher than in the control group (8.2%). Similar studies comparing FMS prevalence in patients with chronic urticaria and healthy volunteers have shown that the FMS incidence in the urticaria group varied between 9.7% and 70.6% (15)(16)(17)(18)(19)(20). In all these studies, a higher FMS prevalence was observed in the urticaria group than in the control group, and, similar to our study, the difference in FMS prevalence between these two groups was statistically significant (15)(16)(17)(18)(19) and DLQI score, FMS prevalence, FMS duration, and the number of sensitive points. ...
... Similar studies comparing FMS prevalence in patients with chronic urticaria and healthy volunteers have shown that the FMS incidence in the urticaria group varied between 9.7% and 70.6% (15)(16)(17)(18)(19)(20). In all these studies, a higher FMS prevalence was observed in the urticaria group than in the control group, and, similar to our study, the difference in FMS prevalence between these two groups was statistically significant (15)(16)(17)(18)(19) and DLQI score, FMS prevalence, FMS duration, and the number of sensitive points. They attributed the relationship between chronic urticaria and FMS to underlying common etiopathogeneses, such as autoimmunity and cutaneous neurogenic inflammation (19). ...
Aim: Autoimmunity, peripheral nerve dysfunction, and neurogenic inflammation are common mechanisms in chronic spontaneous urticaria (CSU) and fibromyalgia syndrome (FMS). We aimed to detect the prevalence of FMS in patients with CSU and to determine whether this prevalence was affected by the severity of urticaria, and dermatology life quality. Materials and methods: Fifty-three patients with CSU and 49 controls were enrolled in this prospective, controlled, cross-sectional study. The severity of CSU was assessed using Urticaria Activity Scores (UAS), and Dermatology Life Quality Index (DLQI) scores were recorded. The 2016 fibromyalgia diagnostic criteria were used for the diagnosis of FMS, and FMS-related functional disability was assessed using the Fibromyalgia Impact Questionnaire (FIQ). Results: Fibromiyalgia prevalence and the FIQ scores were higher in the CSU group than in the control (p=0.033 and p=0.004, respectively). There was no statistically significant difference between the urticaria durations and UAS of CSU with and without FMS (p>0.05), but DLQI scores were statistically significantly higher in CSU with FMS (p=0.007). A statistically significant moderate positive correlation was present between DLQI and FIQ, Widespread Pain Index, and Symptom Severity Scale scores (r=0.500, r=0.408, r=0.469, r=0.507, respectively). Conclusion: The prevalence of FMS and the disability due to FMS was increased in CSU. Furthermore, the FMS prevalence was not affected by the duration and severity of urticaria; however, it was associated with decreased quality of life.
... Torresani ve ark.'nın yaptığı bir çalışmada kronik ürtikerli hastada fibromiyalji sendromu hastaların %70,6'ında ve kontrol grubunda 16%'sında bulunmuştur (14). Bu yüksek oranı, fibromiyaljili hastaların disfonksiyonel kutanöz sinir liflerinin, sırayla dermal mikro damar dilatasyonu ve plazma ekstravazasyonunu tetikleyerek nöropeptidleri serbest bırakabileceği hipotezini ileri sürerek açıklamışlar ve ayrıca, bazı nöropeptitlerin, sinir uçlarını uyaran ve böylece pozitif geri bildirim sağlayan mast hücre degranülasyonu tetiklediğini iddia ederek nörojenik kökenli cilt enflemasyonunun patofizyolojide etken olabileceğini ortaya atmışlardır (14). ...
... Torresani ve ark.'nın yaptığı bir çalışmada kronik ürtikerli hastada fibromiyalji sendromu hastaların %70,6'ında ve kontrol grubunda 16%'sında bulunmuştur (14). Bu yüksek oranı, fibromiyaljili hastaların disfonksiyonel kutanöz sinir liflerinin, sırayla dermal mikro damar dilatasyonu ve plazma ekstravazasyonunu tetikleyerek nöropeptidleri serbest bırakabileceği hipotezini ileri sürerek açıklamışlar ve ayrıca, bazı nöropeptitlerin, sinir uçlarını uyaran ve böylece pozitif geri bildirim sağlayan mast hücre degranülasyonu tetiklediğini iddia ederek nörojenik kökenli cilt enflemasyonunun patofizyolojide etken olabileceğini ortaya atmışlardır (14). Bu bahsedilen hipotezlerin daha ileri ve prospektif laboratuvar çalışmaları ile desteklenmesi gerekmektedir. ...
Amaç: Kronik spontan ürtiker (KSÜ), düşük yaşam kalitesi ile seyreden, kronik, yaygın ve zorlayıcı bir hastalıktır. Bu çalışmanın temel amacı, KSÜ hastalarında, Kronik Yaygın Ağrının (KYA) varlığını araştırmak ve KYA ile KSÜ arasında klinik özellikler, laboratuvar belirteçler, hastalık aktivite skorları ile dermatoloji yaşam kalitesi indeksi (DYKİ) arasındaki olası bağlantıyı ortaya koymaktır. Yöntem: KSÜ' lü 91 hasta, KYA varlığı açısından üçüncü basamak polikliniğinde değerlendirildi. KSÜ’lü hastalarda, KYA (en az üç ay boyunca dört kadran ve aksiyel olmak üzere beş vücut bölgesinden dördünde veya daha fazlasında ağrı) varlığı romatoloji polikliniğinde değerlendirildi. Ayrıca, hastaların anti-nükleer antikor (ANA), eritrosit sedimantasyon hızı, CRP (C-reaktif protein), B12, total IgE ve anti-TPO test sonuçları da analiz edildi. Hastalar hastalığın başlangıcı ve süresi, eşlik eden morbiditeleri, anjioödem varlığı, atopi öyküsü ve uykudan uyandıran gece kaşıntısı yönüyle değerlendirildi. Hastaların hastalık aktivitesini ortaya koymak için ürtiker kontrol testi (UKT), ürtiker aktivite skoru (UAS) ve hekim ve hastaların genel sağlık durumunu ayrı ayrı değerlendirdiği görsel analog skala kullanıldı. Ayrıca, hastaların yaşam kalitesi dermatolojik hastalık yaşam kalite indeksi (DYKİ) ile değerlendirildi. Sonuç: KSÜ’lü 91 hastadan 23'ünde (25.3%) KYA mevcuttu. KYA +, KSÜ' lü hastalarda anlamlı yüksek Doktor Global değerlendirme skoru (p=0.003), Hasta global değerlendirme skoru (p=0.005), UAS (p=0.046), DYKİ (p<0.001) ve düşük UCT skorları bulundu. KYA’lı 23 hastanın dokuzunda, eşlik eden hastalık olarak astım (39.1%) bulundu (p=0.005). Tartışma Ürtiker hastalarında KYA'nın varlığı, hastaların yaşam kalitesini ve hastalık skorlarını olumsuz yönde etkileyebilir.
... Therefore, it can be assumed that neuropeptides may also be playing a role in etiopathogenesis of FMS. Torresani et al. (26) hypothesized that dysfunctional cutaneous nerve fibers of patients with FMS may release neuropeptides. These literature data show that both vitiligo and FMS share similar etiopathogenetic mechanisms (e.g., autoimmun theory, autoantibodies, cytokines, neuropeptides), however up to date no study had evaluated the potential association between vitiligo and FMS. ...
... Several studies have evaluated the prevalence of FMS in some other dermatologic diseases. Torresani et al. (26) revealed that (27) suggested that FMS slightly, but not significantly, more frequent in patients with chronic urticaria and severity of disease was also correlated with duration of FMS symptoms, number of the tender point, FIQ and VAS scores. In contrast to these studies Hapa et al. (28) revealed that the frequency of FMS in chronic urticaria was not increased and they could not find any association with urticaria severity, duration and serum skin test. ...
Objective:This study aimed to determine the relationship between fibromyalgia syndrome (FMS) and vitiligo.
Methods:Thirty-five vitiligo patients and 45 controls were enrolled. All subjects were examined for symptoms and signs of FMS. Clinical and functional evaluations included Fibromyalgia Impact Questionnaire (FIQ), Vitiligo Area Scoring Index (VASI), Pittsburgh Sleep Quality Index (PSQI), visual analogue scale (VAS) and Hospital Anxiety and Depression Scales (HADS).
Results:Vitiligo patients had higher fatigue, depression, anxiety and sleep quality scores (p<0.05). The frequency of FMS was higher in patients with vitiligo than in controls (p=0.015). The vitiligo patients with FMS had significantly higher scores in pain, fatigue, stiffness, FIQ,VASI, HADS and PSQI scores (p<0.05). There were significant correlations between vitiligo severity and other clinical parameters. FIQ,VASI, HADS and PSQI scores were found to be significant predictors of the presence of FMS in patients with vitiligo.
Conclusion:This study revealed that the frequency of FMS was higher in patients with vitiligo. Moreover, the presence of FMS was not only associated with worsening in psychological status and sleep qualities of the vitiligo patients, but also with increased severity of the disease itself. Therefore, clinicians should be aware of FMS as concomitant disease which worsens the clinical and functional outcomes in patients with vitiligo.
... We found higher frequency of FMS in patients with acne than in healthy controls. A literature search revealed that there are three published studies regarding FMS frequency in chronic urticaria, [21][22][23] and one study in psoriasis. 24 However, to the best of our knowledge, there is no study regarding FMS frequency in acne patients. ...
... 24 However, to the best of our knowledge, there is no study regarding FMS frequency in acne patients. Torresani et al. 21 found that 70.6% of patients with chronic urticaria had FMS, but this study did not address FMS-related symptoms. Yener et al. 22 reported that the frequency of FMS was similar between the chronic urticaria patients and healthy controls. ...
Objectives:
This study aims to investigate the frequency of fibromyalgia syndrome and to specify fibromyalgia syndrome-associated clinical symptoms in patients with acne vulgaris.
Patients and methods:
Eighty-eight patients (28 males, 60 females; mean age 23.2±5.1 years; range 18 to 40 years) with acne vulgaris and age, sex- and body mass index-similar 76 healthy controls (14 males, 62 females; mean age 24.5±2.9 years; range 18 to 35 years) were included. Acne vulgaris was evaluated by using the Global Acne Scale, while Hospital Anxiety and Depression Scale was used to evaluate anxiety.
Results:
Fibromyalgia-associated pain, sleep disturbance, anxiety, and menstrual cycle disturbance were significantly more frequent in patients with acne vulgaris than controls. Also, the severity of anxiety and the number of tender points were significantly higher in the acne vulgaris patients than controls.
Conclusion:
This study indicates that patients with acne vulgaris have increased frequency of fibromyalgia syndrome than healthy controls (21.6% versus 5.3%, respectively).
... Torresani et al. 32 included 126 patients with CU in their study and showed that 70% of those with CU also had FM, This proportion is almost two times higher than our results, but this difference may be explained by the different study designs that were used. Patients with DM, thyroid dysfunctions, hematological abnormalities, autoimmune disorders, and other systemic diseases were all included in their study, but we excluded those with a history of any systemic, inflammatory, or autoimmune disorders. ...
... Patients with DM, thyroid dysfunctions, hematological abnormalities, autoimmune disorders, and other systemic diseases were all included in their study, but we excluded those with a history of any systemic, inflammatory, or autoimmune disorders. Unlike Torresani et al. study, 32 we also assessed symptoms such as sleep disturbances, fatigue, morning stiffness, and swollen soft tissues in the patients with CU, since they usually accompany FM, 12,33 and found that the frequency of those symptoms was higher in the patients with CU than for the HCs. Furthermore, we demonstrated restrictions in the QoL in patients with CU. ...
Objectives: Chronic urticaria (CU) and fibromyalgia (FM) are different types of diseases with unclear etiopathogeneses but share many clinical and histochemical features. This study aims to make a recognization on these features and examines whether patients with CU are also affected by FM. Patients and methods: Forty patients with CU and 38 healthy controls were enrolled to this study. All of the participants were assessed according to the 1990 American College of Rheumatology (ACR) classification criteria for FM and asked questions regarding the clinical features of FM. The quality of life was assessed by the Nottingham Health Profile (NHP), while the psychological status was evaluated using the Hospital Anxiety and Depression Scale (HADS). Results: The incidence of FM was higher among the patients with CU (32.5%) than the controls (10.5%) (p=0.019). We indicated that the patients with CU suffered restrictions regarding to quality of life as assessed by the NHP. NHP-sleep (p=0.035), NHP-social isolation (p=0.032) and NHP-emotional reaction (p=0.027) scores were significantly higher compared to HCs. The HADS-depression scores were also significantly higher in the patients with CU (p=0.006). The patients with CU and concomitant FM had higher total NHP scores than those without FM (p<0.001). Conclusion: Clinicians must be alerted to the possible coexistence of FM in CU patients. Patients with CU have higher rates of FM than the general population and this results in more restrictions in daily life in these patients than those with CU alone. Therefore, additional treatment protocols may be required to be implicated for the treatment of patients with both CU and FM.
... Specific neuropeptides in CIU are elevated and associated polymodal and chemosensitive small cutaneous nerve fibers are known to participate in skin inflammation. 12 Neurogenic switching is proposed to result when a sensory impulse from a site of activation is rerouted via the central nervous system (CNS) to a distant location resulting in neurogenic inflammation at a second location. Such a phenomenon is proposed in fibromyalgia pain syndromes. ...
... 17 For patients who do not respond it is recommended that second-line therapies should be added to the antihistamine treatment. 12 Some controlled studies have shown that H 2 -receptor antagonists may provide statistically significant benefit if they are added to H 1receptor antagonists, although others have found only little benefit over anti-H 1 -therapy alone. Immunosuppressive drugs are very effective in most chronic urticaria patients, but their potential toxicity limits a wide clinical use. ...
Chronic idiopathic urticaria (CIU) is a common disease estimated to affect 0.1% of the population and can be very difficult to treat. Many psychotropic medications have been reported to be successful in treating refractory CIU. The purpose of this article was to discuss the pathophysiology of chronic urticaria and provide practicing allergists and dermatologists alternative treatment options in the management of refractory CIU, especially in those who have concurrent psychiatric comorbidity. A review was performed of pertinent literature pertaining to the pathophysiology of CIU and the many psychotropic medications reportedly successful in disease management. Although more research is needed, this article serves to broaden the mind of the physician treating CIU.
... They noted that due to a difference in collagen metabolism, the accumulation of collagen deposits around peripheral nerves may also have reduced pain tolerance in these patients (10). Additionally, there are studies showing that the incidence of fibromyalgia increases in skin patients with skin diseases such as psoriasis, acne vulgaris, rosacea, seborrheic dermatitis, SLE and urticaria, as well as skin findings detected in FMS [11][12][13][14][15][16]. In our study, it was observed that the participants in the FMS group had less skin elasticity and moisture content. ...
... The prevalence rate of FMS among women with acne vulgaris was found to be 30.0% which is higher when compared to a study done by Yazmalar et al. [20] who found FMS was affected 16% of women in his study group, and another study done by Thune [17] who found FMS was affected 13% of women with psoriasis which is another distressing skin disease, and it seems to be low when compared to a study done by Torresani et al. [21] who found the prevalence rate of FMS was 53.9% in women with chronic urticaria. The prevalence rate of FMS in our study population is considered high when compared to the prevalence rate in the control group and in women in the general population [22]. ...
... which is comparable to a study done by Yazmalar et al., (Yazmalar et al., 2016) who found FMS was in 21.6% of his study group. However, the prevalence rate of FMS in patients with acne vulgaris in our study was higher than that in patients with psoriasis (Thune, 2005), and it seems to be low when compared to a study done by Torresani et al. (Torresani et al., 2009), who found the prevalence rate of FMS was 70.6% in patients with chronic urticaria which may be more disressing disease than acne vulgaris, and was lower than that of some rheumatological disorders such as, a prevalence rate of 25% in patients with RA, 30% in patients with SLE, 37.5% in patients with psoriatic arthritis, and 50% in patients with Sjogren syndrome (Wolfe et al., 1984;Middleton et al., 1994;Vitali et al., 1989;Magrey et al., 2013b), difference may be related to the nature of these originally painful disorders. In our study, the prevalence rate is considered high when compared to the that in the general population (Wolfe et al., 1995). ...
1 Rheumatologist. Rheumatology unit in Basrah Teaching Hospital Basrah. Iraq 2 Dermatologist. Dermatology unit in Basrah Teaching Hospital Basrah. Iraq 3 Rheumatologist. Rheumatology unit in Alshifaa General Hospital 4 Rheumatologist, Rheumatology unit in Al sader Teaching Hospital, Basrah. Iraq 5 Rheumatologist, Rheumatology unit in Alfayhaa Teaching Hospital, Basrah. Iraq *Corresponding Author's E-mail: amathkhoor@yahoo.co.uk Widespread pain and fibromyalgia syndrome (FMS) are observed in many patients with autoimmune and inflammatory disorders. The aim of this study was to investigate the prevalence of fibromyalgia and its associated symptoms in patients with acne vulgaris. Ninety-one patients with acne vulgaris and 84 sex and age matched controls were enrolled for the study, the mean age and disease duration of the patient group were 21.75±2.1 and 6.5 ±1.5 years respectively. Acne vulgaris was evaluated by using the Global Acne Scale. A two stage classification process was applied to determine the presence of FMS in patients with acne vulgaris and controls. Stage 1: was answering the diffuse widespread pain questionnaire. In Stage 2, all patients with wide spread pain were examined for 18 tender points. A total of 35 (38.4%) patients with acne vulgaris were found to have widespread pain. A total of 21 patients met the criteria of FMS with a prevalence rate of 23.0%; of them, 18 (85.7%) were women. FMS and its associated symptoms are more prevalent in patients with acne vulgaris than in the general population. Women with acne vulgaris are more frequently affected by FMS. FMS was found to be associated with the severity of acne, and overweight.
... Acute psychological stress may induce CRH-dependent (corticotropin-releasing hormone) mast cell degranulation [12], and stress-related mechanisms may provide links to CIU [13][14][15]. Although psychological stress in isolation is unlikely to be the sole trigger, a high frequency of patients with CIU report a stressful event preceding the onset of CIU [16], and patients with CIU experience high rates of anxiety, depression, and somatoform disorders such as fibromyalgia, with half of subjects with CIU being affected by at least one of these conditions [17,18]. Psychiatric comorbidity appears to significantly increase life quality impairment [19]. ...
Objective:
To assess the efficacy of bloodletting therapy (acupoint pricking and cupping) in patients with chronic idiopathic urticaria (CIU) in a randomized, control, parallel-group trial.
Methods:
A total of 174 patients with CIU enrolled from March 2018 to October 2019 were randomized into three groups: group A treated with bloodletting therapy and ebastine, group B treated with placebo treatment (acupoint pseudopricking and cupping) and ebastine, and group C treated with ebastine only. The intention-to-treat analysis was conducted, and the primary outcome was the effective rate of UAS7 score being reduced to 7 or below after treatment phase.
Results:
The effective rates at the end of treatment phase were different among the three groups (P < 0.05), which were 73.7% in group A, 45.6% in group B, and 42.9% in group C. Multiple analysis indicated differences between groups A and B (P < 0.0125) and groups A and C (P < 0.0125) and no difference between groups B and C (P > 0.0125). No severe bloodletting therapy-related adverse events were observed.
Conclusions:
In this study on patients with CIU, one month of bloodletting therapy combined with ebastine is clinically beneficial compared with placebo treatment combined with ebastine and treatment with ebastine only. Thus, bloodletting therapy can be an effective complementary treatment in CIU. This trial is registered with ChiCTR1800015294.
... The prevalence rate of FMS among women with acne vulgaris was found to be 30.0% which is higher when compared to a study done by Yazmalar et al. [20] who found FMS was affected 16% of women in his study group, and another study done by Thune [17] who found FMS was affected 13% of women with psoriasis which is another distressing skin disease, and it seems to be low when compared to a study done by Torresani et al. [21] who found the prevalence rate of FMS was 53.9% in women with chronic urticaria. The prevalence rate of FMS in our study population is considered high when compared to the prevalence rate in the control group and in women in the general population [22]. ...
in this article we evaluated the presence of fibromyalgia syndrome in women complaining of acne vulgaris and its relation to disease severity
... Pain in fibromyalgia involves neuroinflammatory processes triggered by mast cells and microglia [31][32][33][34][35]. Mounting evidence indeed supports the role of mast cells in fibromyalgia comorbid disorders and painful conditions [6,36,37]. For example, CCL11 (eotaxin) and CCL2 (a potent chemoattractant for mast cells), were found to be elevated in the plasma of fibromyalgia patients [38]. ...
Fibromyalgia is one of the most important “rheumatic” disorders, after osteoarthritis. The etiology of the disease is still not clear. At the moment, the most defined pathological mechanism is the alteration of central pain pathways, and emotional conditions can trigger or worsen symptoms. Increasing evidence supports the role of mast cells in maintaining pain conditions such as musculoskeletal pain and central sensitization. Importantly, mast cells can mediate microglia activation through the production of proinflammatory cytokines such as IL-1β, IL-6, and TNFα. In addition, levels of chemokines and proinflammatory cytokines are enhanced in serum and could contribute to inflammation at systemic level. Despite the well-characterized relationship between the nervous system and inflammation, the mechanism that links the different pathological features of fibromyalgia, including stress-related manifestations, central sensitization, and dysregulation of the innate and adaptive immune responses is largely unknown. This review aims to provide an overview of the current understanding of the role of adaptive immune cells, in particular T cells, in the physiopathology of fibromyalgia. It also aims at linking the latest advances emerging from basic science to envisage new perspectives to explain the role of T cells in interconnecting the psychological, neurological, and inflammatory symptoms of fibromyalgia.
... Increasing evidence supports the involvement of mast cells in FMS (Lucas et al., 2006;Pollack, 2014) and comorbid disorders (Theoharides, 2013) as well as other inflammatory Theoharides et al., 2010a) and painful conditions, (Heron and Dubayle, 2013;Chatterjea and Martinov, 2014) as well as neuroimmune interactions (Skaper et al., 2017) (Figure 1). Chronic urticaria, which involves stimulation of skin mast cells is more common in FMS (Torresani et al., 2009). Moreover, mast cells are significantly increased in the papillary dermis of FMS patients (Blanco et al., 2010). ...
Fibromyalgia Syndrome (FMS) is a disorder of chronic, generalized muscular pain, accompanied by sleep disturbances, fatigue and cognitive dysfunction. There is no definitive pathogenesis except for altered central pain pathways. We previously reported increased serum levels of the neuropeptides substance P (SP) and its structural analogue hemokinin-1 (HK-1) together with the pro-inflammatory cytokines IL-6 and TNF in FMS patients as compared to sedentary controls. We hypothesize that thalamic mast cells contribute to inflammation and pain, by releasing neuro-sensitizing molecules that include histamine, IL-1β, IL-6 and TNF, as well as calcitonin-gene related peptide (CGRP), HK-1 and SP. These molecules could either stimulate thalamic nociceptive neurons directly, or via stimulation of microglia in the diencephalon. As a result, inhibiting mast cell stimulation could be used as a novel approach for reducing pain and the symptoms of FMS.
... However, they found symptom duration longer, FIQ and VAS scores higher in the CIU group. Torresani et al. [15] reported FMS diagnosis in 70% of patients with CIU. CIU is a common skin disorder characterized by spontaneous recurrent well-being and itchy attacks, seriously affecting life quality. ...
Aim: Fibromyalgia syndrome (FMS) and chronic idiopathic urticaria (CIU) are closely related due to peripheral neurogenic inflammation (neuropeptide secretion), immune dysfunction, and somatic complaints such as fatigue, pain, anxiety, and sleep disturbance. This study aimed to reveal the relationship of CIU with FMS, sleep disturbance and anxiety.
Materials and Methods: A total of 51 patients with CIU aged 18–64 years (36.2±10.4) and 45 sex- and age-matched healthy controls were included. Urticaria activity score (UAS) was assessed for the severity of urticaria. The 2010 American College of Rheumatology classification criteria were used for FMS diagnosis. The participants were evaluated with visual analog scale (VAS), fibromyalgia impact questionnaire (FIQ), Pittsburgh sleep quality index (PSQI), and Beck anxiety inventory (BAI).
Results: The presence of FMS and body mass index (BMI) were significantly higher in the urticaria group compared with the control group. The mean FIQ and UAS of the urticaria group were 47.0 ± 22.1 and 1.3 ± 0.9, respectively. UAS was positively correlated with FIQ, PSQI, BAI and VAS (rho=0.411 p=0.004; rho=0.310 p=0.034; rho=0.419 p=0.004; rho=0.414 p=0.004; respectively). The presence of FMS was found to be significantly associated with high BMI (p = 0.04).
Conclusions: The prevalence of FMS was higher in patients with CIU than control group. Also, FMS was more severe, general pain and fatigue, sleep disturbance and anxiety were higher in patients with high urticarial activity.
... In a study by Torresani et al., [18] chronic urticaria was found in 70% of 126 FMS patients. Yener et al. [19] investigated the rate of FMS in 72 patients with chronic urticaria. ...
... (Blanco, et al., 2010) Moreover, chronic urticaria, which involves MCs, has been identified in some FMS patients. (Torresani, et al., 2009) However, the numbers of MCs may not be as important as the degree of their activation or the specific mediators that they secrete. (Theoharides, et al., 2012) Activated MCs release numerous vasoactive, neurosensitizing and pro-inflammatory mediators (Theoharides, et al., 2015f) that could contribute to FMS symptoms. ...
Fibromyalgia Syndrome (FMS) is a chronic, idiopathic condition of widespread musculoskeletal pain, affecting more women than men. Even though clinical and laboratory studies have provided evidence of altered central pain pathways, the lack of definitive pathogenesis or objective diagnostic markers has hampered development of effective treatments. Here we report for the first time that the neuropeptides corticotropin-releasing hormone (CRH), substance P (SP) and its structurally related Hemokinin-1 (HK-1) were significantly (p=0.026, p<0.0001 and p=0.002, respectively) elevated (0.82±0.57 ng/mL, 0.39±0.18 ng/mL and 7.98±3.12 ng/mL, respectively) in the serum of patients with FMS as compared to healthy controls (0.49±0.26 ng/mL, 0.12±0.1 ng/mL and 5.71±1.08 ng/mL, respectively). Moreover, SP and HK-1 levels were positively correlated (Pearson's r=0.45, p=0.002). The serum concentrations of the inflammatory cytokines IL-6 and TNF were also significantly (p=0.029 and p=0.006, respectively) higher (2.97±2.35 pg/mL and 0.92±0.31 pg/mL, respectively) in the FMS group as compared to healthy subjects (1.79±0.62 pg/mL and 0.69±0.16 pg/mL, respectively). In contrast, serum IL-31 and IL-33 levels were significantly lower (p=0.0001 and p=0.044, respectively) in the FMS patients (849.5±1005 pg/mL and 923.2±1284 pg/mL, respectively) in comparison to healthy controls (1281±806.4 pg/mL and 3149±4073 pg/mL, respectively). Our results indicate that neuro-inflammation may contribute to the symptoms of FMS patients, especially since we had previously shown that CRH and SP are known to stimulate IL-6 and TNF release from mast cells. Treatment directed at preventing the secretion on antagonizing these elevated neuroimmune markers may be useful in the management of FMS patients.
... Ayrıca, fibromiyalji sendromunda olduğu gibi kronik ürtiker etyolojisinde de emosyonel stresin önemli bir rol oynadığı düşünülmektedir 10 . Ancak, kronik ürtiker ile fibromiyalji sendromunun birlikteliğini inceleyen İngilizce literatürde sadece bir çalışma mevcuttur 9 . Yukarıda bahsi geçen bilgiler doğrultusunda, biz bu çalışmada hem etyolojide hem de patogenezde ortak noktaları olduğu bilinen bu iki hastalığın birlikteliğini araştırmayı ve bu birlikteliğin hastalık şiddetinden etkilenip etkilenmediğini belirlemeyi amaçladık. ...
Background and designIn recent years, there are studies about role of dysfunctioning of the peripheral cutaneous nevre fibres in the etiology of chronic urticaria. Similiarly to urticaria, dysfunctioning of peripheral cutaneous nevre fibres was also charged in etiology of fibromiyalgia syndrome which was accepted to be the one of the chronic pain syndromes.The aim of this study was to assess the frequency of fibromiyalgia syndrome in patients with chronic urticaria and to show whether this incidence was affected from clinical findings of urticaria.Material and method50 patients with chronic urticaria and 48 controls were included into the study. Besides an autologous serum skin test, urticaria activity score (UAS) was calculated for the evaluation of the severity of the disease. The diagnosis of fibromiyalgia syndrome was made in accordance to American Collage of Rheumatology 1990 criteria. Patients are also divided into 2 groups according to disease duration and UAS.Results26% of the patients with chronic urticaria and 20.8% of the control group have fibromiyalgia syndrome and no significant difference was observed between each group (p=0.715). There was also no significant difference between patients with positive autologous serum skin test and patients with negative autologous serum skin test. When the patients divided into 2 groups according to UAS were compared with respect to frequency of fibromiyalgia syndrome, no significant difference was observed (p=0.197). Furthermore, when the patients divided into 2 groups according to disease duration were compared with respect to frequency of fibromiyalgia syndrome, there was also no significant difference (p=0.645).Conclusion
In conclusion, contrast to the recently reported study, we observed that frequency of fibromiyalgia syndrome does not increase in chronic urticaria and this frequency was not effected from the severity of urticaria, disease duration and positivity of autologous serum skin test.Key words: chronic urticaria, fibromiyalgia, frequency
... The number of MCs was significantly increased in the papillary dermis of FMS patients (Blanco et al., 2010). Moreover, chronic urticaria, which involves MCs, is more common in FMS (Torresani et al., 2009). ...
Fibromyalgia Syndrome (FMS) is a chronic, idiopathic condition of widespread musculoskeletal pain, affecting primarily women. It is clinically characterized by chronic, non-articular, pain and a heightened response to pressure along with sleep disturbances, fatigue, bowel and bladder abnormalities, as well as cognitive dysfunction. The diagnostic criteria have changed repeatedly and there is neither definitive pathogenesis nor reliable diagnostic or prognostic biomarkers. Clinical and laboratory studies have provided evidence of altered central pain pathways. Recent evidence suggests the involvement of neuroinflammation with stress peptides triggering the release of neurosenzitizing mediators. The management of FMS requires a multidimensional approach including patient education, behavioral therapy, exercise, and pain management. Here we review recent data on the pathogenesis and propose new directions for research and treatment.
The American Society for Pharmacology and Experimental Therapeutics.
... Although psychological stress in isolation is unlikely to be the sole trigger, a high frequency of patients with CsU report a stressful event preceding the onset of CsU [31] and the possibility of a causal influence of emotional distress, especially of stressful life events, on the course of skin diseases has long been postulated [32]. Patients with CsU experience high rates of anxiety, depression and somatoform disorders such as fibromyalgia, with half of subjects with CsU being affected by at least one of these conditions [33,34]. Psychiatric comorbidity appears to significantly increase QoL impairment [35]. ...
This guidance for the management of patients with chronic urticaria and angioedema has been prepared by the Standards of Care Committee of the British Society for Allergy and Clinical Immunology (BSACI). The guideline is based on evidence as well as on expert opinion and is aimed at both adult physicians and paediatricians practising in allergy. The recommendations are evidence graded. During the development of these guidelines, all BSACI members were included in the consultation process using a Web-based system. Their comments and suggestions were carefully considered by the Standards of Care Committee. Where evidence was lacking, a consensus was reached by the experts on the committee. Included in this management guideline are clinical classification, aetiology, diagnosis, investigations, treatment guidance with special sections on children with urticaria and the use of antihistamines in women who are pregnant or breastfeeding. Finally, we have made recommendations for potential areas of future research.
© 2015 John Wiley & Sons Ltd.
... It is worth mentioning that skin rashes were seen among 25 % of patients with fibromyalgia who completed an internet survey conducted by bennett et al. [24]. In another study, 70 % of patients with chronic urticaria were shown to be suffering from fibromyalgia; a finding that made the authors suggest that chronic urticaria could be a consequence of fibromyalgia which could trigger neurogenic skin inflammation [25]. Celiac disease has been associated with both dermatitis herpetiformis and with aphthous stomatitis [26], the former being considered as an acute manifestation of celiac disease. ...
Fibromyalgia is a chronic pain syndrome associated with numerous somatic symptoms including gastrointestinal manifestations of nonspecific nature. Celiac disease and nongluten sensitivity frequently evolve in adults with gastrointestinal and extraintestinal symptoms similar to those found among patients with fibromyalgia. The objective of the present study was to evaluate the presence of celiac-type symptoms among patients with fibromyalgia in comparison with healthy subjects and with those experienced by adult celiac patients and subjects with gluten sensitivity. A list of typical celiac-type symptoms was developed, comparing the frequency of presentation of these symptoms between patients with fibromyalgia (N = 178) and healthy subjects (N = 131), in addition to those of celiac patients and gluten-sensitive patients reported in the literature. The frequency of presentation of every celiac-type symptom, excepting anemia, was significantly higher among patients with fibromyalgia compared to controls (p < 0.0001). Regarding the existing data in the literature, the prevalence of fatigue, depression, cognitive symptoms and cutaneous lesions predominated among patients with fibromyalgia, whereas the prevalence of gastrointestinal symptoms was higher among patients with fibromyalgia compared to gluten-sensitive patients and was similar among patients with fibromyalgia and celiac disease patient. The symptomatological similarity of both pathologies, especially gastrointestinal symptoms, suggests that at least a subgroup of patients with fibromyalgia could experience subclinical celiac disease or nonceliac gluten intolerance.
... Although both CIU and FMS are postulated to be autoimmune disorders, there are limited and contradictory data on the potential association between CIU and FMS. In a pilot study, Torresani et al. [21] aimed to determine whether patients with CU were also affected by FMS. The study included a total of 126 patients with CU, and the authors found that, unexpectedly, over 70% of patients with CU had FMS. ...
Background:
The pathophysiology of chronic idiopathic urticaria (CIU) is not fully understood; however, it has been hypothesized that a subset of people with CIU may have an autoimmune disease and that peripheral cutaneous nerve fibers may be involved in CIU. Similarly, it has been postulated that fibromyalgia syndrome (FMS) is an autoimmune disorder and may be associated with alterations of peripheral cutaneous nerve fibers. Accordingly, the present study aimed to determine whether the frequency of FMS is higher in patients with CIU.
Material/methods:
A total of 72 patients with CIU and 67 sex- and age-matched healthy controls were included. Urticaria activity score (UAS), fibromyalgia impact questionnaire (FIQ), tender point number, and visual analogue scale (VAS) were assessed.
Results:
The frequency of FMS was similar between the groups (9.7% vs. 4.5%, p=0.32). However, symptom duration of FMS was significantly longer, and tender point number and FIQ were significantly higher in patients with CIU than in controls. In addition, patients with CIU had significantly higher VAS scores. UAS was significantly correlated with presence of FMS, symptom duration of FMS, tender point number, and FIQ and VAS scores. Logistic regression analysis revealed that UAS was an independent predictor of presence of FMS (b=0.34, p=0.003).
Conclusions:
Frequency of FMS was slightly, but not significantly, higher in patients with CIU than in controls. However, symptom duration of FMS, tender point number, and FIQ and VAS scores were significantly higher in patients with CIU, and UAS reflecting severity of the disease was significantly and independently associated with presence of FMS.
... Anecdotally, we find that many patients with fibromyalgia have ill-defined itch and/or burning sensation over various parts of the body with no secondary causes being found. Although a recent study found that fibromyalgia was present in 70% of patients with chronic urticaria, 79 there was no evidence of a dermatologic cause for the itch in these patients. This itch is likely functional in nature, a similar expression of the underlying psychological processes resulting in fibromyalgia. ...
... Smaller studies have found comorbidity between fibromyalgia and the following conditions: migraine in females but not males [111], primary headache [64], chronic fatigue symptom [89], systemic lupus erythematosus [213], irritable bowel syndrome [144], rheumatoid arthritis [183], the premenstrual syndrome [3], chronic urticaria [235] and cervical myofascial pain syndrome [40]. Comorbidity has been shown also for back pain and temporomandibular disorders [248], migraine and temporomandibular disorders [91], irritable bowel syndrome and functional dyspepsia, fibromyalgia and chronic pelvic pain [185], and finally between migraine and irritable bowel syndrome, chronic fatigue and fibromyalgia [232]. ...
Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways, the phenomenon of central sensitization. Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia, aftersensations, and enhanced temporal summation. It can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin, muscles or viscera, and in addition to producing pain hypersensitivity, results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques. Studies in clinical cohorts reveal changes in pain sensitivity that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia, osteoarthritis, musculoskeletal disorders with generalized pain hypersensitivity, headache, temporomandibular joint disorders, dental pain, neuropathic pain, visceral pain hypersensitivity disorders and post-surgical pain. The comorbidity of those pain hypersensitivity syndromes that present in the absence of inflammation or a neural lesion, their similar pattern of clinical presentation and response to centrally acting analgesics, may reflect a commonality of central sensitization to their pathophysiology. An important question that still needs to be determined is whether there are individuals with a higher inherited propensity for developing central sensitization than others, and if so, whether this conveys an increased risk in both developing conditions with pain hypersensitivity, and their chronification. Diagnostic criteria to establish the presence of central sensitization in patients will greatly assist the phenotyping of patients for choosing treatments that produce analgesia by normalizing hyperexcitable central neural activity. We have certainly come a long way since the first discovery of activity-dependent synaptic plasticity in the spinal cord and the revelation that it occurs and produces pain hypersensitivity in patients. Nevertheless, discovering the genetic and environmental contributors to and objective biomarkers of central sensitization will be highly beneficial, as will additional treatment options to prevent or reduce this prevalent and promiscuous form of pain plasticity.
Mast cells are important components of the immune system, and they perform pro-inflammatory as well as anti-inflammatory roles in the complex process of immune regulation in health and disease. Because of their strategic perivascular localization, sensitivity and adaptability to the microenvironment, and ability to release a variety of preformed and newly synthesized effector molecules, mast cells perform unique functions in almost all organs. Additionally, Mast cells express a wide range of surface and cytoplasmic receptors which enable them to respond to a variety of cytokines, chemicals, and pathogens. The mast cell’s role as a cellular interface between external and internal environments as well as between vasculature and tissues is critical for protection and repair. Mast cell interactions with different immune and nonimmune cells through secreted inflammatory mediators may also turn in favor of disease promoting agents. First and forefront, mast cells are well recognized for their multifaceted functions in allergic diseases. Reciprocal communication between mast cells and endothelial cells in the presence of bacterial toxins in chronic/sub-clinical infections induce persistent vascular inflammation. We have shown that mast cell proteases and histamine induce endothelial inflammatory responses that are synergistically amplified by bacterial toxins. Mast cells have been shown to exacerbate vascular changes in normal states as well as in chronic or subclinical infections, particularly among cigarette smokers. Furthermore, a potential role of mast cells in SARS-CoV-2-induced dysfunction of the capillary-alveolar interface adds to the growing understanding of mast cells in viral infections. The interaction between mast cells and microglial cells in the brain further highlights their significance in neuroinflammation. This review highlights the significant role of mast cells as the interface that acts as sensor and early responder through interactions with cells in systemic organs and the nervous system.
Amaç: Kronik ürtiker nedeni tam olarak aydınlatılamamışkaşıntılıbir deri hastalığıdır. Otoimmünite ve psikojenik faktörlerin de patogenezde rolü olabileceği düşünülmektedir. Fibromiyaljisendromu (FMS)psikojenik nedenlerle ilişkili olabileceği düşünülen bir romatizmal hastalıktır. Çalışmamızda kronik ürtiker hastalarında FMS sıklığı ve şiddetini araştırmayı planladık. Araçlar ve Yöntem: Çalışmaya kronik ürtiker tanısı almış ve sistemik hastalık öyküsü olmayan 100 hasta ve yaş ve cinsiyet açısından eşleştirilmiş 100 sağlıklı kontrol dahil edildi. Hastaların demografik bilgileri ve hastalık süreleri kaydedildi. Ürtiker şiddeti dermatoloji yaşam kalite indeksi skorları (DYKI) hesaplanarak değerlendirildi.Klinik şiddet ve fonksiyonel disabilite durumlarıvizuel analog skala (VAS) ve fibromiyalji etki anketi (FIQ) ile değerlendirildi. Bulgular: Hasta grubunun yaş ortalaması 37.7±1.32, kontrol grubunun ise 40.7±11.2olarak saptandı (p=0.09). Hasta grubundaki FMS sıklığı (% 45) kontrol grubundan (% 13) istatistiksel olarak anlamlı şekilde yüksekti(p=0.00).FMS ve ürtiker süreleri arasında istatistiksel olarak anlamlı fark saptanmadı(p=0.902). Kronik ürtiker süresi FMS’lihastalarda istatistiksel olarak anlamlı derecede yüksek bulundu(p=0.001). FIQ ve DLQI değerleri arasında istatistiksel olarak anlamlı korelasyon saptandı(p=0.019). Hasta ve kontrol grubunda FMS süreleri, VAS ve FIQ açısından istatistiksel olarak anlamlı fark saptanmadı (p=0.432, p=0.201, p=0.332). Sonuç: Kronik ürtiker hastalarında FMS sıklığının artmış olduğunu görülmektedir. Bu sonuç kronik ürtiker patogenezindeki nöromediatörlerin kronik dönemdeki etkileriyle ilişkili olabilir.
Chronic spontaneous urticaria (CSU) is characterized by spontaneous occurrence of wheals without an obvious stimulus that lasts for most days of week for more than 6 weeks. It is the most common subtype of chronic urticaria, with point prevalence between 0.5% and 1%. The exact etiopathogenesis of CSU remains poorly understood. Some of the possible causes of CSU include acute or chronic infections, pseudo allergies to food and drugs, allergic reactions to medications, insect bites and stings, and autoimmunity including autoimmune thyroid disorders. There is significant evidence of functional IgG autoantibodies directed against IgE or the high-affinity IgE receptor in 25-30% of patients in CSU. In around half the cases of CSU, even after exhaustive panel of investigations, the cause may still remain elusive. Nevertheless, some characteristic lab findings may help to point towards the possible cause. Like, increased ESR suggests the possibility of an underlying systemic disease or infection, whereas, eosinophilia should prompt search for any parasitic infection. Similarly, screening test for thyroid function along with anti-TPO and anti-TG levels when done in appropriate cases, can at times yield a positive result. Clinically, it is characterized by presence of evanescent wheals with or without angioedema. While wheals are erythematous, completely blanchable evanescent plaques of various sizes, angioedema is result of dermal and subcutaneous edema. The wheals are associated with itching and occasionally burning sensation. They are migratory in nature. Angioedema is present in 40-50% of cases. Preferred first line treatment of CSU are newer generation H1 antihistamines. These include cetirizine, loratadine, desloratadine, fexofenadine and mizolastine. However, in pregnancy, chlorpheniramine and diphenhydramine are preferred oral and intravenous antihistamines respectively. In case of no response, the dose can be raised up to four times the standard doses. Short course oral corticosteroids like prednisolone in the dose of 0.3-0.5 mg/kg, tapered over 4-6 weeks can be given in recalcitrant cases. Leukotriene receptor antagonist, Zafirleukast in dose of 20 mg twice daily and Monteleukast in dose of 10 mg once a day have shown superior efficacy in patients with urticaria aggravated by pseudoallergens. Biologic agents like omalizumab have also shown promising results in resistant cases of CSU, not controlled by any other drugs.
Purpose: The aim was to investigate the skin findings in patients with Fibromyalgia Syndrome (FMS), and the relations of these findings with the clinical symptoms of the disease, quality of life and depression levels of the patient.
Materials and Methods: A total of 77 patients with FMS were included in the study as the study group, 74 individuals were included as the control group. The pain levels were evaluated with Visual Analogue Scale (VAS). The short form-36 (SF-36) was used to evaluate the quality of life levels of the patients. The Beck Depression Scale (BDS) was used to evaluate the depression levels of the patients. All participants were evaluated by the same dermatology specialist.
Results: Although 37.1% patients who had FMS had at least one cutaneous symptom, 19.9% of the control group had at least one cutaneous symptom (p<0.01). According to the BDS, significant increases were detected in FMS patients (p=0.001). Significant decreases were detected in terms of all SF-36 parameters in the FMS group (p=0.001). There was at least one dermatological disease in 43% of the patients, and in 20.5% of the controls. Although no significant differences were detected between BDS and VAS scores of the FMS patients with and without dermatological findings, SF-36 total score and physical role strength score were found to be significantly lower in the patients who had dermatological symptoms.
Conclusions: It must be known that there may be dermatological symptoms in FMS, a more multidisciplinary approach must be used in treatment and follow-up.
Purpose:
The aim of this study was to evaluate the effects of a dietary supplement containing primarily an extract of salmon's milt (semen) on symptoms and blood levels of proinflammatory molecules in patients with fibromyalgia syndrome (FMS), a chronic, painful musculoskeletal disease without a distinct pathogenesis or treatment. We recently reported increased serum levels of the proinflammatory molecules substance P (SP) and tumor necrosis factor (TNF) in patients with FMS as compared to those in normal controls.
Methods:
This prospective, open-label study was conducted in patients with FMS (n = 87; 80 women, 7 men; age range, 18-80 years) selected from 2 clinical centers in Spain. Patients were administered the supplement and were evaluated at weeks 1 (before treatment), 4, 8, and 12 (end of treatment) for clinical parameters of functioning, fatigue, and pain, as well as overall impression. Patients were directed to take 1 capsule per day in the morning for the first 4 weeks, followed by 1 capsule in the morning and 1 capsule in the evening for the remaining 8 weeks. Differences in symptom scores in patients with FMS between weeks 1 and weeks 4, 8, and 12 were evaluated using ANOVA. Blood was obtained and serum separated in patients with FMS at 1 and 12 weeks and in a separate population of healthy controls (n = 20; 15 women, 5 men; age range, 25-65 years). Serum levels of SP and TNF were measured in patients with FMS at 1 and 12 weeks and in healthy controls by ELISA. TNF and SP levels in patients with FMS were compared between weeks 1 and 12, as well as between patients with FMS and untreated controls, using the Mann-Whitney U test.
Findings:
Clinical parameters of functioning, fatigue, and pain, as well as overall impression, were improved significantly at 4 weeks as compared to 1 week and remained unchanged for the duration of the study (all, P < 0.0001). Serum TNF and SP levels were significantly elevated at 1 week in patients with FMS compared to controls and were decreased significantly at 12 weeks as compared to 1 week (all, P < 0.0001).
Implications:
Our findings indicate that this dietary supplement may significantly improve symptoms in patients with FMS. This is the first time to our knowledge that any molecule has been reported to be associated with a reduction in serum SP level. Consequently, the supplement or its hypothesized main active ingredient, spermine, may be developed as a novel treatment approach to FMS or other neuroinflammatory conditions. ClinicalTrials.gov identifier: NCT03911882.
The Central Sensitization (CSI) Inventory was introduced in 2012. It was initially intended as a screener to help identify when presenting symptoms may be related to central sensitization or indicate the presence of a central sensitivity syndrome. It has now been translated and validated in a number of European, Asian, and South American languages. This article provides an overview of CSI rationale, development, recommended uses, and research results, including evidence of validity and reliability, in clinical and non‐clinical subject samples.
Introduction: Fibromyalgia (FM) is a chronic disorder whose symptoms of pain, fatigue, sleep disturbances and depression have a devastating effect on patients’ lives as it limits their ability to engage in everyday working and social activities, and make it difficult to maintain normal relationships with family, friends and employers. None of the currently available drugs are fully effective against the whole spectrum of symptoms. The aim of this narrative review is to summarise the data relating to the new therapeutic options that have become available over the last few years.
Areas covered: Increasing efforts by the pharmaceutical industry have led to the introduction of new investigational drugs and new formulations of older drugs, and studies have been carried out in order to investigate the possibility of using drugs that are currently used for other diseases.
Expert Opinion: Slight improvements in the health of FM patients treated with drugs targeting a range of molecular mechanisms have been observed, but there is still no single drug that is capable of offering substantial efficacy against all of the characteristic symptoms of FM. The identification of new and improved therapies for FM requires consideration of the heterogeneity of the condition, which suggests the existence of different patient subgroups, a relationship between central and peripheral aspects of the pathophysiology, and the need for combined treatment with drugs targeting multiple molecular mechanisms.
Fibromyalgia (FM) represents one of a group of soft tissue pain disorders that affect muscles and soft tissues, such as tendons and ligaments. The widespread body pain is usually associated with a number of manifestations that include fatigue, headache, sleep disorders, and cognitive disturbances. FM is not uncommon. In spite of being under-recognized, it is estimated to affect 2–3% of the worldwide general population. The multiple symptoms of FM are shared with numerous other medical disorders such as autoimmune rheumatic diseases, psychiatric disorders, and other chronic pain conditions. Additionally, there is no measurable or perceived structural damage, and patients have no diagnostic imaging or laboratory abnormal results. For the aforementioned reasons, most of FM patients are, at least initially, subject to wrong or delayed diagnosis. The existence of a comorbidity with a disease can significantly entangle its course starting from puzzling the diagnosis and ending with worsening the prognosis. FM has been linked to a broad spectrum of disorders that occur in FM patients in a higher frequency than that of the control populations. These disorders include cervical spondylosis, low back pain, spondyloarthropathies, rheumatoid arthritis, systemic lupus erythematosus, obesity, obstructive sleep apnea, hypertension, and last but not least coronary atherosclerosis. On the other hand, FM appreciably coexists with a list of diseases that are mainly autoimmune, chronic inflammatory, or rheumatic diseases, including but not limited to rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, psoriatic arthritis, and inflammatory bowel disease. We here discuss the mutual impact of FM and its comorbidities from the diagnostic, therapeutic, prognostic, and future research points of view.
Fibromyalgia appears to present in subgroups concerning biological pain induction with primarily inflammatory, neuropathic/neurodegenerative, sympathetic, oxidative, nitrosative or muscular factors and/or central sensitization. Recent research also discussed a glial activation or interrupted dopaminergic neurotransmission as well as increased skin mast cells and mitochondrial dysfunctions. Therapy is difficult and the treatment options used so far mostly just have the potential to address only one of these aspects. As Ambroxol addresses all of them in a single substance and furthermore also reduces visceral hypersensitivity, in fibromyalgia existing as irritable bowel syndrome or chronic bladder pain, it should be systematically investigated for this purpose. Encouraged by first clinical observations of two working groups using topical or oral ambroxol for fibromyalgia treatments the present paper outlines the scientific argumentation for this approach by looking at each of the above mentioned aspects of this complex disease and summarizes putative modes of action of ambroxol. Nevertheless at this point the evidence basis for ambroxol is currently not strong enough for clinical recommendation.
Background/Objective: Fibromyalgia syndrome (FMS) is a chronic, generalized pain condition characterized with widespread soft-tissue pain, fatigue, sleep disturbances, and tender points on physical examination. Although, there are numerous articles about the frequency of FMS in dermatologic diseases such as psoriasis and chronic urticaria, few studies have been reported concerning skin findings in FMS. Our objective was to evaluate the skin findings and skin-related symptoms in FMS patients and determine the quality of life in FMS patients with dermatologic diseases.
Methods: A total 105 female patients ages between 18 years and 65 years and diagnosed with FMS were included in the study. A total of 105 healthy volunteers were age and sex matched in the control group.
Results: Skin related symptoms such as pruritus, burning, tingling, and increased sweating were more common in FMS patients than in the control group. Xerosis, dermographism, lichen simplex chronicus, neurotic excoriations, tinea pedis, and seborrheic dermatitis were more frequent in FMS patients and the differences were statistically significant. Presence of dermatologic disease or skin-related symptoms in FMS patients did not affect the quality life of the FMS patients.
Conclusion: Genetic and pathophysiological studies to clarify the relationship between FMS and dermatologic disorders will provide more information on the association and common treatment of these disorders.
Samuel Hafenreffer, 350 years ago, named pruritus as a "harmful sensation triggering a scratch desire". Today such a definition is likely to be still useful, although a lot of studies have been performed, in the last decades, about this interesting topic. It is now clear, first of all, that itch is built, on the basis of stimuli coming from the skin or not, at a central level. In fact, pruriceptive afferent primary fibers coming from the skin are able to bind, in the posterior horn of medulla, secondary pruriceptive neurons which project to the talamus, whereas from talamus tertiary neurons project to cortex. Cortex localizes itch in the somato-sensorial I region, while the scratch centers are localized in pre-motory anterior cortex. From anterior cingulus, moreover, fibers projecting to pre-frontal area or to orbito-frontal area trigger effective responses to itch. On the other hand, skin is still the classic and specific area in which itching stimuli can arise. Specifically, epidermis in toto can be regarded, in others' and our opinion, as a true large and unique "receptor", able to capture a lot of external stimuli through a variety of receptors, and consequently release a set of mediators. These mediators themselves can represent stimuli for receptors expressed on the surface of the free endings of nervous fibers localized within the epidermis and the dermis; from these stimulated nervous receptors stimuli can thus arise able to trigger both the excitation of pruriceptive fibers toward the central nervous system, and the syntesis and release of neuropeptides, which are able to stimulate mast cells. Indeed, we believe that mast cells mainly represent a sort of "resonance box", which amplifies the pruritogenic stimuli voyaging from the epidermis to the neurons. In fact, mast cell receptors favour, under the stimulation by mediators coming from both nerve endings and keratinocytes, the syntesis and the release of mast cell mediators which bind specific receptors expressed on the nerve endings themselves: a "virtue circle" thus arises among keratinocytes, nerve endings, and mast cells, favouring the cutaneous onset of pruritogenic stimuli. Another source of itch, apart from the above mentioned "activation of pruriceptors", can be the "sensitization of nociceptors". In fact, peripheral pain mediators become able, when nociceptive peripheral neurons are "sensitized", to trigger pruritogenic, other/rather than painful, stimuli. This is, e.g., the case of "sprouting" of peripheral nervous fibers, which favours their prolonged sensitization. Moreover, a "central", other than "peripheral", sensitization exists, which opens the scenarios named "hyperknesis" and even "alloknesis": such scenarios focus the relationships between pain and itch, with consequent therapeutic opportunities, hopefully valuable for the treatment of a number of itch conditions utilizing the same drugs able to treat pain conditions. On the other hand, itch can be inhibited by a series of mediators: the two main such mediators are cannabinoids, as well as hyperactive vanilloids. Vanilloids, in fact, in normal conditions stimulate, other than inhibit, a series of pruriceptive ionic-channel-receptors, generally shared by nervous endings, keratinocytes and leukocytes. In our opinion, every itch-associated disease can have a specific repertoire of mediators, receptors and neurobiological pathways: the recognition of these specific repertoires may hopefully favour the assessment of a series of consequent therapeutic repertoires, which could be specific for each itch-associated disease.
Mast cell infiltrates in tissues of vulvodynia are common, but they have not been characterized for criteria of neoplastic mast cell disease or correlated with patient's concomitant diseases associated with increased mast cells. Formalin-fixed specimens of 35 patients with vulvodynia were evaluated immunohistochemically with antibodies to CD 3,4,8,20,117c and human mast cell tryptase, and for WHO-criteria of neoplastic mastocytosis (>25% spindled mast cell, CD25 expression, point mutations of the c-kit gene (D816V), and chronically elevated serum tryptase levels). Only 20/35 specimens showed a T-lymphocyte dominant inflammatory infiltrate on HE-stained sections, but all showed mast cells. 4/35 biopsies showed <10 mast cells/mm(2) , 15/35 specimens 40-60 mast cells/mm(2) and 16/35 specimens >60 mast cells/mm(2) (average 80/mm(2) ). Control tissue contained typically <10 mast cells/mm(2) . Spindling, CD25-expression, c-kit gene mutations, or increased serum tryptase levels were not detected. 26/35 (74%) patients had concomitant autoimmune diseases, psoriasis, atopy, various allergies, preceding infections. Independent of the subtype of vulvodynia, the majority of mast cell rich biopsies with >40 mast cells/mm(2) were classified as a secondary mast cell disorder reflecting an activated immune system in 75% of vulvodynia patients. Patients with increased mast cells may benefit from medical therapy targeting mast cells.
© 2015 APMIS. Published by John Wiley & Sons Ltd.
Öz
Aim: Recent studies showed increased axon reflex flare reaction to mechanical and chemical stimuli associated with neurogenic inflammation in patients with fibromyalgia (FM). Pathergy test is identified as a non-specific hypersensitivity reaction to minimal trauma. The purpose of this study was to investigate whether patients with FM had a positive pathergy test or not.
Methods: Forty-six patients who met the 1990 American College of Rheumatology (ACR) criteria for the classification of FM and fifty-one healthy control subjects (HCs) were included in this study. Twenty-eight patients with Behcet’s disease were included as disease control for Pathergy test. The Fibromyalgia Impact Questionnaire (FIQ) was used for assessment of functional status in patients with FM. The Nottingham Health Profile was used for assessment of quality of life in all subjects.
Results: There was no significant difference in demographic characteristics between the three groups (p > 0.05). NHP-pain, NHP-physical mobility, NHP-energy, NHP-emotional reaction, NHP-sleep and NHP-total scores were significantly higher in patients with FM compared to HCs (p < 0.001). Neither patients with FM nor HCs had a positive pathergy test.
Conclusion: There are some pathophysiological changes in the skin biopsies of patients with FM; however, these changes are not accompanied by a positive pathergy test.
Key Words: Fibromyalgia, Pathergy test
Migraine is a very disabling condition that can severely impair quality of life. Eighteen percent of women suffer from migraine headaches, and of those, approximately 60% have migraines near the time of their menstrual period. Migraine is generally undertreated, not only because some sufferers do not have access to proper care, but also because many fail to seek treatment because of misperceptions that nothing can be done for a condition from which generations of women have suffered. Research has shown that migraine is not a disorder of blood vessels, but rather a brain disorder characterized by inflammation. The goal of this paper is to explain practical approaches to managing menstrual migraine.
When a 36-year-old woman with fibromyalgia syndrome (FMS) underwent the tuberculin test, urticaria developed on her trunk at 30 min after intradermal injection of purified protein derivative. Although the urticaria resolved, fever, facial edema, and generalized urticaria occurred after 8 h. A patient with FMS who developed a systemic allergic reaction after an intradermal skin test has not been reported. We should pay attention to anaphylactic reactions after intradermal injection in patients with FMS.
Chronic urticaria (CU) is a disturbing allergic condition of the skin. Although frequently benign, it may sometimes be a red flag sign of a serious internal disease. A multitude of etiologies have been implicated in the causation of CU, including physical, infective, vasculitic, psychological and idiopathic. An autoimmune basis of most of the 'idiopathic' forms is now hypothesized. Histamine released from mast cells is the major effector in pathogenesis and it is clinically characterized by wheals that have a tendency to recur. Laboratory investigations aimed at a specific etiology are not always conclusive, though may be suggestive of an underlying condition. A clinical search for associated systemic disease is strongly advocated under appropriate circumstances. The mainstay of treatment remains H1 antihistaminics. These may be combined with complementary pharmacopeia in the form of H2 blockers, doxepin, nifedipine and leukotriene inhibitors. More radical therapy in the form of immunoglobulins, plasmapheresis and cyclophosphamide may be required for recalcitrant cases. Autologous transfusion and alternative remedies like acupuncture have prospects for future. A stepwise management results in favorable outcomes. An update on CU based on our experience with patients at a tertiary care centre is presented.
Central sensitization (CS) has been proposed as a common pathophysiological mechanism to explain related syndromes for which no specific organic cause can be found. The term "central sensitivity syndrome (CSS)" has been proposed to describe these poorly understood disorders related to CS. The goal of this investigation was to develop the Central Sensitization Inventory (CSI), which identifies key symptoms associated with CSSs and quantifies the degree of these symptoms. The utility of the CSI, to differentiate among different types of chronic pain patients who presumably have different levels of CS impairment, was then evaluated. Study 1 demonstrated strong psychometric properties (test-retest reliability = 0.817; Cronbach's alpha = 0.879) of the CSI in a cohort of normative subjects. A factor analysis (including both normative and chronic pain subjects) yielded 4 major factors (all related to somatic and emotional symptoms), accounting for 53.4% of the variance in the dataset. In Study 2, the CSI was administered to 4 groups: fibromyalgia (FM); chronic widespread pain without FM; work-related regional chronic low back pain (CLBP); and normative control group. Analyses revealed that the patients with FM reported the highest CSI scores and the normative population the lowest (P < 0.05). Analyses also demonstrated that the prevalence of previously diagnosed CSSs and related disorders was highest in the FM group and lowest in the normative group (P < 0.001). Taken together, these 2 studies demonstrate the psychometric strength, clinical utility, and the initial construct validity of the CSI in evaluating CS-related clinical symptoms in chronic pain populations.
Objective. To determine if abnormal collagen metabolism is correlated with neurogenic inflammation, a potential activator of collagen metabolism, in patients with fibromyalgia (FM). Methods. The presence of inflammatory cytokines, interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TN-F)-alpha was investigated in skin tissues by using reverse transcription-polymerase chain reaction (RTPCR) and immunohistochemistry. Fifty-three skin biopsies from female patients with FM (30-65 years of age) were examined and compared to skin biopsies of 10 age and sex matched healthy controls. Biopsies were obtained from the left deltoid region. Rheumatoid arthritis synovial fibroblasts and tissues were used as positive controls for the expression of cytokines. Total RNA isolated from the tissue samples were reverse transcribed (RT) by random hexamers as the primer for RT followed by PCR amplification using specific primers for IL-1beta, IL-6 or TNF-alpha. Expression of IL-1beta, and TNF-alpha protein was investigated in the skin by immunohistochemistry using specific antibodies (avidin-biotin method). Results. Positive signals (RT-PCR) were detected in skin tissues of 19/50 (38%) FM patients for IL-1beta, in 14/51 FM patients (27%) for IL-6, and in 17/53 patients (32%) for TNF-alpha. None of the cytokines could be detected in healthy control skin. Immunoreactivity for IL-1beta and TNF-alpha was demonstrated in certain skin tissues of our FM patients. Conclusion. The detection of cytokines in FM skin indicates the presence of inflammatory foci (neurogenic inflammation) in the skin of certain patients (about 30% of FM patients), suggesting an inflammatory component in the induction of pain. This may explain the response to nonsteroidal antiinflammatory therapy in a subset of FM patients.
Fibromyalgia has been reported to occur with high prevalence in systemic lupus erythematosus. Data on fibromyalgia in other subsets of lupus erythematosus are not available. Risk factors for fibromyalgia have not been defined. We investigated 60 patients with different subsets of lupus erythematosus for the presence of fibromyalgia, association with clinical and laboratory parameters and disease activity. Our data were compared with the multicentre lupus erythematosus registry at the Free University of Berlin. Ten out of 60 patients with more than 11 tender points and widespread pain for more than 3 months were classified as positive for fibromyalgia. All of them were female. Fibromyalgia-positive patients suffered significantly more often from headache, morning stiffness, diffuse alopecia, muscle pain, arthralgia, renal involvement, and disclosed peripheral blood cell cytopenia, rheumatoid factor, hypergammaglobulinaemia and intake of corticosteroids and azathioprine. Fibromyalgia was more frequent in systemic lupus than in other lupus subsets. Evaluation of fibromyalgia symptoms and lupus disease activity was performed in 30 patients in a 1-year (range 9-13 months) follow-up. These 30 patients consisted of 9 fibromyalgia-positive and 21 fibromyalgia-negative patients. Both groups were characterized by stable clinical features such as number of tender points and ECLAM index. Fibromyalgia did not show a correlation with lupus activity. We suggest that fibromyalgia and lupus erythematosus are distinct complaints. Patients with lupus are at risk of developing secondary fibromyalgia. The clinical features of fibromyalgia-positive patients may contribute to misinterpretation of lupus activity.
Nerve-mast cell interaction is involved in both homeostatic and pathologic regulations. The molecules that sustain this association have not been identified. Because synaptic cell adhesion molecule (SynCAM), alternatively named spermatogenic Ig superfamily (SgIGSF), is expressed on both nerves and mast cells and because it binds homophilically, this molecule may be a candidate. To examine this possibility, mast cells with or without SgIGSF/SynCAM were cocultured with superior cervical ganglion neurons that express SgIGSF/SynCAM, and the number of mast cells attached to neurites was counted. The attachment of mast cells with SgIGSF/SynCAM, i.e., bone marrow-derived mast cells (BMMC) from wild-type mice, was inhibited dose-dependently by blocking Ab to SgIGSF/SynCAM. Mast cells without SgIGSF/SynCAM, i.e., BMMC from microphthalmia transcription factor-deficient mice and BMMC-derived cell line IC-2 cells, were defective in attachment to neurite, and transfection with SgIGSF/SynCAM normalized this. When the nerves were specifically activated by scorpion venom, one-quarter of the attached IC-2 cells mobilized Ca(2+) after a few dozen seconds, and ectopic SgIGSF/SynCAM doubled this proportion. At points of contact between neurites and wild-type BMMC, SgIGSF/SynCAM was locally concentrated in both neurites and BMMC. SgIGSF/SynCAM on mast cells appeared to predominantly mediate attachment and promote communication with nerves.
This article discusses scientific evidence supporting the notion that all fibromyalgia (FM) features can be explained on the basis of autonomic (sympathetic) nervous system dysfunction. Also suggests that FM main features (widespread pain and tenderness at palpation on specific anatomic points) are manifestations of painful neuropathy. On these bases, a holistic approach for FM treatment is proposed.
Accumulating evidence has so far indicated that cross-talk between the nervous and immune systems plays a pivotal role in the pathophysiology of various diseases. As a prototypic demonstration of neuro-immune systems, the interaction between nerves and mast cells has been examined intensively. Anatomically, mast cells are often located in close proximity to nerves. Functionally, both cells communicate with each other in a bi-directional manner. Substance P released from nerves and proteases and cytokines from mast cells have proved to be important mediators in such communication. On the other hand, the molecules involved in membrane-membrane contacts between nerves and mast cells were largely unknown. In 2003, both cells were found to express the identical adhesion molecule, named SynCAM (synaptic cell adhesion molecule) or SgIGSF (spermatogenic immunoglobulin superfamily). Since SgIGSF/SynCAM binds homophilically, its involvement in nerve-mast cell interaction was examined in vitro. Superior cervical ganglia expressed SgIGSF/SynCAM along their neurites. Adhesion to these neurites of mast cells lacking SgIGSF/SynCAM was poor, and this was normalized by ectopic expression of SgIGSF/SynCAM. Moreover, SgIGSF/SynCAM-expressing mast cells were more competent in communicating with the neurites. Further understanding of the adhesion molecule-dependent interaction will be expected to open a new avenue in the field of neuro-immune cross-talk.
Syndromes characterized by chronic pain and fatigue have been described in the medical literature for centuries. Fibromyalgia is the term currently used to describe this symptom complex, and considerable research has been performed in the last decade to delineate the epidemiology, pathophysiology, and genesis of this entity. Although fibromyalgia is defined by its musculoskeletal features, it is clear that there are a large number of non-musculoskeletal symptoms, such that we now understand that there is considerable overlap with allied conditions such as the chronic fatigue syndrome, migraine and tension headaches, irritable bowel syndrome, and affective disorders. This article will review our current state of knowledge regarding fibromyalgia and these allied conditions, and present a unifying hypothesis that describes both the pathophysiology of symptoms and the genesis of these disorders.
To develop criteria for the classification of fibromyalgia, we studied 558 consecutive patients: 293 patients with fibromyalgia and 265 control patients. Interviews and examinations were performed by trained, blinded assessors. Control patients for the group with primary fibromyalgia were matched for age and sex, and limited to patients with disorders that could be confused with primary fibromyalgia. Control patients for the group with secondary-concomitant fibromyalgia were matched for age, sex, and concomitant rheumatic disorders. Widespread pain (axial plus upper and lower segment plus left- and right-sided pain) was found in 97.6% of all patients with fibromyalgia and in 69.1% of all control patients. The combination of widespread pain and mild or greater tenderness in ⩾ 11 of 18 tender point sites yielded a sensitivity of 88.4% and a specificity of 81.1%. Primary fibromyalgia patients and secondary-concomitant fibromyalgia patients did not differ statistically in any major study variable, and the criteria performed equally well in patients with and those without concomitant rheumatic conditions. The newly proposed criteria for the classification of fibromyalgia are 1) widespread pain in combination with 2) tenderness at 11 or more of the 18 specific tender point sites. No exclusions are made for the presence of concomitant radiographic or laboratory abnormalities. At the diagnostic or classification level, the distinction between primary fibromyalgia and secondary-concomitant fibromyalgia (as defined in the text) is abandoned.
A subungual solitary glomus tumour was examined by both light and electron microscopy. By light microscopy, typical tumour tissue was seen, surrounded by connective tissue. By electron microscopy, a very close morphological relationship was noted between non-myelinated nerve fibres and mast cells. These mast cells could be divided into two groups: the mast cells of the first group contain numerous mature granules and show few lamellopodia. The distance to the nerve fibre bundles ranged between 2000 and 20 nm. In the second group, the mast cells always showed direct contact with nerve fibers. They had many lamellopodia and contained almost exclusively immature granules. In some cases, invaginations of lamellopodia and broader cytoplasmatic processes into the view that mast cells may play an important part in the function of neurons.
Mechanically induced vasodilatation or flare on the skin, known as dermatographia, is a common clinical observation in fibrositis syndrome and is thought to be a neurogenically mediated axon reflex response. In our study, mechanically and chemically induced flares were quantitated in 13 patients with fibrositis syndrome and 14 control subjects. There was a reduced threshold for chemically induced flare response and the area of flare was greater in patients compared to controls, although there was a wide range of responses in both groups. There was also a significant positive correlation between mechanically and chemically induced flares, and the number of tender points in all subjects correlated with the size of the chemically induced flare. We suggest that exaggerated neurogenic inflammatory responses in patients with fibrositis syndrome reflect increased activity of polymodal nociceptors of unmyelinated primary afferent nerves. This increased receptor activity may also contribute to the pain and tenderness experienced by these patients.
The aim of this chapter is to briefly summarize the earlier and recent evidence, which suggest that polymodal nociceptors and other capsaicin-sensitive (CS) sensory receptors subserve an unorthodox dual sensory-effector function with important neuroregulatory relevance. Sensory receptors are nerve terminals, which are specialized by definition to receive stimuli from the inner or outer environment and convey this information to the central nervous system or some peripheral neural circuitry. A modem version of this orthodox uni-directional neuroregulatory arrangement is completed also by a bi-directional influence of chemical synapses in a self-modifiable way, emphasizing the importance of long-term retrograde signals, for example, in synaptic plasticity or in back diffusion of nitrogen monoxide signal molecules. In spite of all these considerations, including pre-synaptic modulation of neurotransmission at efferent autonomic nerve terminals, transmission of messages to the central nervous system could not be achieved through neuroeffectors, and in terms of neuroregulation, they do not have dual sensory-efferent function.
The etiology of chronic urticaria is unknown, and an exogenous allergen cannot be identified as the cause in the vast majority of subjects. Thus the concept has evolved that it might be autoimmune.
We have prospectively assessed sera obtained from 50 consecutive patients with chronic urticaria for the presence of autoantibodies that could be pathogenic.
We tested sera for their ability to release histamine from human basophils and to activate rat basophil leukemia cells that were transfected with the alpha subunit of the IgE receptor. We also tested selected sera for anti-IgE antibodies and for IgG anti-Fc epsilon RI alpha by Western blot.
Sera from 38 of 50 patients with chronic urticaria released beta-hexosaminidase from transfected rat basophil leukemia cells, whereas only one of 20 control sera did so (p < 0.001); in 30 subjects this could be attributed to IgG anti- Fc epsilon RI alpha. When human basophils were used, sera from 20 of 50 patients with chronic urticaria released a significant quantity of histamine compared with one of 20 control subjects (p < 0.01). Six patients with chronic urticaria and one control subject had IgG anti-IgE. In selected sera we could demonstrate IgG anti-Fc epsilon RI alpha by Western blot; however, some sera are positive for histamine release but do not demonstrate such binding.
A large fraction of patients with chronic urticaria have antibody directed to Fc epsilon RI alpha that is functional (60%). A smaller number have IgG anti-IgE (10%). A third group may also have circulating factors capable of activating basophils or mast cells of which the identity is unknown. Thus chronic urticaria may be autoimmune in origin.
Skin biopsies from 25 patients with fibromyalgia, 5 healthy controls, 8 patients with rheumatoid arthritis, and 9 patients with local chronic pain after whiplash injury, were examined for the occurrence of IgG deposits and collagen types, using direct and indirect immunofluorescence, and for dermal connective tissue mast cells, using semithin Epon sections. Fibromyalgia skin biopsies had significantly higher values of IgG deposits in the dermis and vessel walls and showed a higher reactivity for collagen III. They also had a higher mean number of mast cells. There was a correlation between the percentage of damaged/degranulated mast cells and the individual IgG immunofluorescence scores. These findings support the hypothesis of neurogenic inflammation involvement in fibromyalgia.
Inflammatory cells and their mediators are known to contribute to neuropathic pain following nerve injury. Mast cells play a key role in non-neural models of inflammation and we propose that mast cells and their mediators (in particular histamine) are important in the development of neuropathic pain. In rats, where the sciatic nerve was partially ligated, we showed that stabilisation of mast cells with sodium cromoglycate reduced the recruitment of neutrophils and monocytes to the injured nerve and suppressed the development of hyperalgesia. Treatment with histamine receptor antagonists suppressed the development of hyperalgesia following nerve injury and alleviated hyperalgesia once it was established. These results suggest that mast cell mediators such as histamine released within hours of nerve injury contribute to the recruitment of leukocytes and the development of hyperalgesia.
Recent findings have shed new light on the role of peripheral nerves in the skin and established a modern concept of cutaneous neurobiology. Closely related monodirectional and/or bidirectional pathways exist in which the central and peripheral nervous system, the endocrine and immune system, and almost all skin cells are involved. Information is emerging about the factors involved in these immunomodulatory mechanisms, which are defined as neuropeptides, neurotransmitters, neurotrophins, and neurohormones. The interaction between peripheral nerves and the immune system is mediated by different types of cutaneous nerve fibers that release neuromediators and activate specific receptors on target cells in the skin such as keratinocytes, mast cells, Langerhans cells, microvascular endothelial cells, fibroblasts, and infiltrating immune cells. These interactions influence a variety of physiologic and pathophysiologic functions including cellular development, growth, differentiation, immunity, vasoregulation, leukocyte recruitment, pruritus, and wound healing. A variety of mechanisms lead to the termination of cellular responses to released neuropeptides under physiologic circumstances. Herein, we highlight some of the recent advances of neurocutaneous biology and discuss the role of nerves in mediating cutaneous inflammation. Understanding the mechanisms and the factors controlling neuromediators and their receptors and degrading enzymes will lead to the identification of novel therapeutic targets for the treatment of cutaneous diseases.
Itching is defined as an unpleasant cutaneous sensation leading to the desire to scratch. It serves as a physiological self-protective mechanism as do other cutaneous sensations like pain, touch, vibration, cold, and heat to help defend the skin against harmful external agents. Pruritus can be evoked in the skin directly by mechanical and thermal stimuli or indirectly through chemical mediators. It may also be generated in the central nervous system independently of peripheral stimulation. Single-nerve-fiber recordings have shown that histamine-evoked itch is transmitted by selective slow-conducting subpopulations of unmyelinated C-polymodal neurons. Recent experimental studies using improved methods have demonstrated which of the suspected chemical itch mediators such as histamine, neuropeptides, prostaglandins, serotonin, acetylcholine, or bradykinin act pruritogenically on C-fibers. Moreover, investigations have revealed new receptor systems such as vanilloid, opioid, and cannabinoid receptors on cutaneous sensory nerve fibers that may modulate itch and thereby represent targets for antipruritic therapy. This review focuses on the peripheral generation of itch, including neurotransmitters, neuropeptides, and inflammatory mediators.
The aim of the present study was to investigate the prevalence of fibromyalgia and allied symptoms in patients with psoriasis. During a 3-year period from 1997 until 2000, 1269 patients were consecutively diagnosed with psoriasis. All patients were questioned about musculoskeletal symptoms and those with such symptoms were further examined according to a standardized protocol. In total 335 of 1269 patients had musculoskeletal symptoms. More women than men had such complaints, 33% versus 18.5%, respectively. As many as 13% of the women fulfilled the American College of Rheumatology 1990 (ACR-90) criteria for fibromyalgia, while 14.1% had symptoms compatible with chronic widespread pain without meeting the fibromyalgia criteria. In total, 8.3% suffered from fibromyalgia and 9% from chronic widespread pain. The results indicate that fibromyalgia and allied symptoms are frequent in female patients with psoriasis and constitute important problems with regard to disability and health-related quality of life. Only 35 of 105 patients with fibromyalgia had previously been diagnosed with psoriasis and the diagnostic label of fibromyalgia was new to 51 of them. Female patients with symptoms of psoriasis and pain seem to constitute a subgroup which deserves further studies.
Recent studies have gained widespread information about the complex regulation of genetic, environmental, immunologic, and pharmacologic factors that contribute to the development of allergic inflammatory skin diseases such as atopic dermatitis. Neuroimmune mechanisms, however, still remain to be elucidated. This review will focus on the interaction between the cutaneous immune and peripheral nervous system in allergic inflammatory skin such as atopic dermatitis.
Neuropeptides and neuropeptide-positive nerve fibres are prominently increased in lesions of atopic dermatitis. The density of nerve fibres is increased while peripheral nerve endings are in an active state of excitation. In this regard, neurotrophins particularly described for their functional role on nerve cells are also expressed in atopic dermatitis skin. In addition, neurotrophins modulate the functional role of eosinophils as main target effector cells in atopic dermatitis, as described recently. Interestingly, eosinophils are capable of neurotrophin as well as neuropeptide production itself, pointing to a bidirectional communication between neuronal cell populations and main target effector cells.
Neurotrophins and neuropeptides modulate both the functional activity of sensory neurons and immune cells. We have therefore developed the concept of a neuroimmune network between target effector cells and sensory nerves that links pathogenic events to dysfunctions of the cutaneous immune and peripheral nervous system in allergic inflammatory skin diseases.
Tissue damage, inflammation or injury of the nervous system may result in chronic neuropathic pain characterised by increased sensitivity to painful stimuli (hyperalgesia), the perception of innocuous stimuli as painful (allodynia) and spontaneous pain. Neuropathic pain has been described in about 1% of the US population, is often severely debilitating and largely resistant to treatment. Animal models of peripheral neuropathic pain are now available in which the mechanisms underlying hyperalgesia and allodynia due to nerve injury or nerve inflammation can be analysed. Recently, it has become clear that inflammatory and immune mechanisms both in the periphery and the central nervous system play an important role in neuropathic pain. Infiltration of inflammatory cells, as well as activation of resident immune cells in response to nervous system damage, leads to subsequent production and secretion of various inflammatory mediators. These mediators promote neuroimmune activation and can sensitise primary afferent neurones and contribute to pain hypersensitivity. Inflammatory cells such as mast cells, neutrophils, macrophages and T lymphocytes have all been implicated, as have immune-like glial cells such as microglia and astrocytes. In addition, the immune response plays an important role in demyelinating neuropathies such as multiple sclerosis (MS), in which pain is a common symptom, and an animal model of MS-related pain has recently been demonstrated. Here, we will briefly review some of the milestones in research that have led to an increased awareness of the contribution of immune and inflammatory systems to neuropathic pain and then review in more detail the role of immune cells and inflammatory mediators.
Pruritus (itch) can be defined as an unpleasant cutaneous sensation associated with the immediate desire to scratch. Recent findings have identified potential classes of endogenous "itch mediators" and establish a modern concept for the pathophysiology of pruritus. First, there in no universal peripheral itch mediator, but disease-specific sets of involved mediators. Second, numerous mediators of skin cells can activate and sensitize pruritic nerve endings, and even modulate their growth. Our knowledge of itch processing in the spinal cord and the involved centers in the central nervous system is rapidly growing. This review summarizes the current information about the significance of neuron-skin interactions, ion channels, neuropeptides, proteases, cannabinoids, opioids, kinins, cytokines, biogenic amines, neurotransmitters, and their receptors in the pathobiology of pruritus. A deeper understanding of these circuits is required for the development of novel antipruritic strategies.
The mechanisms responsible for symptom expression in fibromyalgia (FM) are complex. The most consistently detected objective abnormalities in FM involve pain-processing systems. Up to recently, central nervous system was a primary focus of investigations in FM. Although it is unlikely that FM occurs because of primary disorders of the peripheral tissues, there are still data to suggest that some abnormalities can be detected in the periphery. With the recognition of abnormalities in skin of some FM patients, it is now apparent that the role of peripheral nerve endings in FM is much greater than previously thought. The aim of this paper is to review literature concerning the skin biopsy findings of FM patients and discuss their potential relevance to FM. This paper suggests that patients with FM represent a state of the dysfunction of descending, antinociceptive pathways and low hypothalamic-pituitary-adrenal function. This state is further proposed to result in many skin biopsy findings associated with the disorder, including increased N-methyl-d-aspartate receptors subtype 2D expression, neurogenic inflammation and characteristic electron microscopic findings. Future direction of research would be identification of specific laboratory markers such as skin biopsy for diagnostic and clinical evaluation purposes in FM.
Our objectives were to investigate thyroid abnormalities and autoimmunity in 120 patients affected by fibromyalgia (FM) and to study their relationships with clinical data and symptoms. Thyroid assessment by means of antithyroglobulin antibodies, antithyroid peroxidase antibodies, free triiodo-thyronine, free thyroxine, and thyroid stimulating hormone analyses was carried out. The clinical parameters "Fibromyalgia Impact Questionnaire", pain, tender points, fatigue, and other symptoms, and the presence of depression or anxiety disorders were evaluated. The basal thyroid hormone levels of FM patients were in the normal range, while 41% of the patients had at least one thyroid antibody. Patients with thyroid autoimmunity showed a higher percentage of dry eyes, burning, or pain with urination, allodynia, blurred vision, and sore throat. Correlations found between thyroid autoimmunity and age or with the presence of depression or anxiety disorders were not significant. However, in the cohort of post-menopausal patients, the frequency of thyroid autoimmunity was higher with respect to pre-menopausal patients. In conclusion, autoimmune thyroiditis is present in an elevated percentage of FM patients, and it has been associated with the presence of typical symptoms of the disease.
This blinded study was done to determine if there are any abnormal electron microscopic (EM) findings in the skin of fibromyalgia syndrome (FMS) patients, which might contribute to or be due to the increased pain sensitivity seen in this condition. Skin biopsy samples were obtained from 13FMS patients and 5 control subjects. All tissues were prepared for EM examination by immediate prefixation in 2.5% glutaraldehyde for 2 h and postfixation in 1% osmium acid for 24 h. Ultrathin sections on grids were stained by uranylacetate and lead citrate. Biopsies were read by an individual without knowledge of participant status. Five skin biopsies from healthy controls showed relatively even distribution of variegated sized unmyelinated axons sheathed well by complicatedly folded Schwann cell membranes. In tissues from 9/13 FMS patients, unmyelinated Schwann cells were noted to be ballooned, whereas this finding was not noted in any controls (p=0.029). Axons in most patients trended towards being localized in the periphery of the unmyelinated Schwann cell sheaths (p=0.002). Particularly, peripheral localization of axon in the unmyelinated Schwann cell sheath had a strong relationship with ballooning of Schwann cell (p=0.042), simplified folding of Schwann cell sheath (p=0.039) and smaller axon (p=0.034). Myelinated nerve fibers were unremarkable. The EM findings seen in the skin of FMS patients show unusual patterns of unmyelinated nerve fibers as well as associated Schwann cells. If these findings are replicated in a larger study, these abnormalities may contribute to, or be due to, the lower pain threshold seen in FMS patients.
Hein 18. G. Fibromyalgia in lupus erythematosus Association 19. of chronic urticaria and angioedema with thyroid autoimmunity
- A Gräfe
- U Wollina
- B Tebbe
- H Sprott
- C Uhlemann
- Josse Rg
- J Denburg
- J Dolovich
Gräfe A, Wollina U, Tebbe B, Sprott H, Uhlemann C, Hein
18.
G. Fibromyalgia in lupus erythematosus. Acta Derm Venereol 1999; 79: 62–64.
leznoff A, Josse rG, Denburg J, Dolovich J. Association
19.
of chronic urticaria and angioedema with thyroid autoimmunity. Arch Dermatol 1983; 119: 636–640.