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Immunoreactivity as assessed by indirect immunofluorescence with sera in non-dermal tissues. (a–c) The parathyroid gland: (a) serum from a palmoplantar pustulosis (PPP) patient with endothelial immunoreaction; (b) serum from a healthy non-smoking person, no endothelial staining; (c) double staining (PPP serum and endothelial cell antibodies), yellow colour demonstrates that PPP serum reacts with endothelial cells; (d) thyroid gland – immunoreactivity in the endothelium between the follicles; (e) pancreas – strong staining of the endothelial cells lining the lumen of a larger blood vessel. Scale bars: (a–c) 10 µm; (d) 20 µm; (e) 10 µm.
Source publication
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Citations
... This speculation was supported by the favorable outcome in a clinical trial using secukinumab (anti-IL-17A antibody) or guselkumab (anti-IL-23 antibody) for PPP patients; however, the limited efficacy showed that other factors were also involved in PPP pathogenesis. 65,66 Hyperimmune response of TMC to autoantigens such as keratin and heat shock proteins and tonsillar crypt epithelium Several possible autoantigens for PPP have been studied in the last decades; antibodies to the epithelial cytoplasm in the horny layer, 67 papillary epithelial cytoplasm in palmar skin 68 and keratin, which is one of the main constituent proteins of the horny layer, 69 are reportedly present in PPP patient sera. Furthermore, the deposition of Ig, complements and immune complexes were seen in the pustular areas of PPP patients. ...
Palmoplantar pustulosis (PPP) is characterized by symmetrical, erythematous, scaly plaques, with numerous, sterile, non‐bacterial, pinpoint pustules, which are restricted to the palms and soles. Because several reports have described the efficacy of tonsillectomy for improvement in PPP skin lesions, we consider that PPP is tonsil‐induced autoimmune/inflammatory syndrome (TIAS) while other factors are also involved in the pathogenesis of PPP. Here, the association between PPP pathogenesis and TIAS was examined, with a focus on results of previous studies. PPP patients show a hyperimmune response to indigenous bacteria such as α‐streptococci, due to impaired immunological tolerance towards such organisms. Such a novel immune response leads to T‐cell activation through the abnormal expression of secondary stimulation molecules, including cytotoxic T‐lymphocyte‐associated antigen 4, inducible T‐cell co‐stimulator and Smad7, in the tonsils of PPP patients. Activated tonsillar T cells express cutaneous lymphocyte antigen (CLA), CCR6 and β1‐integrin, enter the blood circulation and are recruited to PPP skin lesions. Within lesions, T cells roll onto endothelial cells through the interaction between CLA and E‐selectin, migrate into the extravascular area through β1‐integrin–vascular cell adhesion molecule 1 binding, and assemble in the skin through CCL20–CCR6 binding. Hyperimmune responses to autoantigens such as keratin and heat shock proteins could also be involved in PPP pathogenesis, through the stimulation of the T‐helper 17 reaction.
... However, an association between chronic inflammatory osteitis and psoriasis, a chronic, immune-mediated inflammatory skin disease has been consistently observed [6,11,[19][20][21]. Moreover, palmoplantar pustulosis (which is frequently present in SCCH patients) has been proposed to be an autoimmune disease in its own right [22,23]. ...
Background
Sternocostoclavicular hyperostosis (SCCH; ORPHA178311) is a rare inflammatory disorder of the axial skeleton, the precise pathophysiology of which remains to be established. We addressed the potential association of SCCH with autoimmune processes by evaluating the lifetime prevalence of autoimmune disease in 70 patients with adult-onset SCCH and 518 SCCH-unaffected first-degree relatives (parents, siblings and children). Danish hospital registry data for autoimmune diseases were used as reference data.
Results
The mean age of interviewed patients was 56.3 years (range 26–80 years) and 86% were female. Interviewed patients belonged to 63 families, with four families having clusters of 2–3 patients. A diagnosis of at least one autoimmune disease was reported in 20 SCCH patients (29%) and in 47 relatives (9.1%), compared to an estimated 3.9% prevalence of autoimmune disease in the Danish reference population. A diversity of autoimmune diseases was reported in SCCH patients and relatives, most frequently psoriasis vulgaris (14%). Palmoplantar pustulosis was reported by 28 patients (40%). In SCCH patients, inclusion of palmoplantar pustulosis as putative autoimmune disease increased the overall prevalence to 54%.
Conclusions
The high prevalence of autoimmune disease in patients with sternocostoclavicular hyperostosis and their first-degree relatives suggests that autoimmunity may play a role in the still elusive pathophysiology of the intriguing osteogenic response to inflammation observed in this rare bone disorder.
... also indicative of a possible autoimmune response against these vessels. The concomitant presence of Bcl-2 at this level indicates an active cell cycle struggle between cell cycle regulators, proto-oncogenes, and apoptotic mechanisms. [25] Our observed immune reactivity to endothelial cells has been previously documented in palmoplantar psoriasis. [26] The possible autoimmune effects on blood vessels on psoriatic skin thus warrants further investigation, especially given additional documented associations of cardiovascular alterations in psoriatic patients versus controls groups.272829 In summary, the possible genetic factors and environmental stimuli that trigger the immune response ...
A characteristic feature of early active psoriatic lesions is the intraepidermal penetration of neutrophils, with attendant formation of Munro-Saboureau microabscesses. Previous immunofluorescence studies have shown reactivity of in vivo binding of stratum corneum antibodies (SCAs) within the Munro-Saboreau microabscesses in cases of psoriasis.
In our study, we aimed to investigate any correlation between the SCAs and the Munro-Saboureau microabscesses.
We investigated 50 archival biopsies of psoriasis with Munro-Saboureau microabscesses, and attempted to confirm antibody colocalization within these microabcesses via immunohistochemistry staining. As controls, we utilized 50 skin biopsies from healthy patients undergoing esthetic plastic surgery procedures.
Within the Munro-Saboureau microabscesses, the following markers were statistically significantly positive relative to controls: CD1a, CD8, CD23, cyclooxygenase-2, myeloid histoid antigen, albumin, fibrinogen, kappa, lambda, von Willebrand factor, IgG, IgM, IgD, complement/C3c, C3d, myeloperoxidase, and carcinoembryonic antigen (P < 0.05). Autoreactivity to blood vessels was also detected, with multiple immunoglobulins and complement factors.
We document important correlations between the Munro-Saboureau microabscesses, SCAs, and other immunoreactants.
Background:
Association of palmoplantar pustulosis (PPP) with metabolic and autoimmune diseases has been reported in mostly small case series or anecdotal cases.
Objective:
To assess health-related quality of life and prevalence of comorbidities in a large cohort of PPP patients.
Methods:
We conducted a cross-sectional study on patients with either active or past PPP. Disease severity was measured by the Palmoplantar Pustulosis Area and Severity Index (ppPASI). Quality of life was assessed by the Dermatology Life Quality Index (DLQI). Comorbidities were evaluated by medical history, blood examination, stool testing for Helicobacter pylori antigen and screening tools for depression and psoriatic arthritis.
Results:
A total of 102 patients (87 women, 15 men) with a mean age of 52.6 ± 14.1 years were evaluated. The mean DLQI was 7 ± 6. Comorbidities were frequent and consisted of hypercholesterolemia (38%), hypertension (32%), obesity (27%), metabolic syndrome (26%), depression (24%), diabetes (19%), autoimmune thyroiditis (16%) and psoriatic arthritis (16%).
Conclusion:
Patients with PPP have an impaired quality of life and a broad range of comorbidities. Contrary to other reports our investigation failed to show an association between PPP and coeliac disease or H. pylori infection. This article is protected by copyright. All rights reserved.
Palmoplantar pustulosis is characterized by a chronic eruption of sterile pustules on palms and soles. The disease affects mainly women in the sixth and seventh decade of life. Some authors consider palmoplantar pustulosis a separate entity, whereas others consider it a condition in the spectrum of psoriasis. Aim of this study was to summarize the most recent data about PPP which aimed at establishing the nosological position of palmoplantar pustulosis. A systematic search of published literature was carried out. General characteristics of patients with PPP in different populations were present. We reviewed histological, immunological and genetic studies, as well as treatment options for PPP. PPP presents with clinical features, which are not present in psoriasis; however, the common coexistence of psoriasis vulgaris and/or positive family history for psoriasis indicates at least a close relationship between PPP and psoriasis. At present, there are not sufficient data to exclude PPP from psoriasis group.
Pustular lesions of palms and soles (pustulosis palmoplantaris - PPP) are a chronic condition with an unspecified nosological position. Some researchers consider it as a variant of psoriasis, whereas others indicate numerous distinctions and consider PPP as a separate entity. Genetic investigations support exclusion of PPP from the psoriasis group. Among concepts of PPP aetiopathogenesis, the one concerning the role of sweating and the theory about PPP as a cutaneous manifestation of a generalized autoimmunological process demand attention. A typical patient is a woman 50-60 years old, a smoker, suffering from thyroid disease. Among other disorders associated with PPP disturbed calcium homeostasis and presence of anti-gliadin antibodies are observed. Among numerous systemic and topical therapies retinoids present the highest, but not satisfactory effectiveness. Attempts to use biological treatments are made as well, but due to the insufficient number of references it is impossible to draw conclusions about their effectiveness. An interesting issue is onset or exacerbation of pustulosis palmoplantaris type of lesions or psoriasis induced by TNF-α antagonist therapy. Further studies on aetiopathogenesis and treatment of PPP are necessary.
Palmoplantar pustulosis (PPP) is a chronic, recurrent and difficult to treat skin condition characterized by the presence of pustules, erythema, and hyperkeratosis on palms and soles.
Fifteen subjects with PPP were randomized (2:1) to receive subcutaneous injections of either etanercept 50 mg or a placebo twice a week for 3 months. All subjects then received the etanercept 50 mg injections twice a week for an additional 3 months.
Etanercept was well tolerated by subjects with PPP. The decrease in median Palmoplantar Pustulosis Area and Severity Index (PPPASI) score from baseline to 24 weeks was statistically significant for subjects treated with etanercept for 24 weeks (P = 0.038, n = 10) but not for subjects in the placebo/etanercept cross-over group (P = 0.125, n = 5). Comparison of changes in PPPASI from baseline to week 12 was not statistically significant for subjects assigned to etanercept or to placebo. Some subjects treated with etanercept presented good clinical improvements in PPP severity whereas others showed an increase in PPP severity.
This study showed that etanercept was well tolerated in subjects with PPP and suggests that some PPP subjects might benefit from etanercept therapy. Larger studies are needed to assess PPP response to etanercept including the influence of smoking and the presence or absence of psoriasis outside palms and soles.
Palmoplantar pustulosis (PPP) is probably the inflammatory skin disease most strongly associated to smoking. The disease is common in middle-aged, smoking women, and is chronic, sometimes disabling and characterized by pustules, erythema and scaling on the soles and palms. It is often treatment-resistant. PPP patients have a co-morbidity with an increased risk of autoimmune thyroid disease, celiac disease/gluten intolerance, abnormal calcium homeostasis, diabetes type 2, and depression. The sweat gland apparatus is involved in the pathogenesis of PPP since a) the normal structure of the acrosyringium is abolished so the keratin pattern differs to that in normal palmar skin; b) granulocytes migrate outwards in the acrosyringium forming the pustule in the stratum corneum. Acetylcholine (ACh) is the main inducer of sweating. With immunohistochemistry the ACh synthesizing enzyme choline acetyltransferase (ChAT) and the ACh-degrading enzyme acetylcholinesterase (AChE) were found to be strongly expressed in the gland and duct as were the alpha-3 and alpha-7 nicotinic acetylcholine receptors (nAChRs). Smoking influenced the staining intensity of the enzymes and the alpha-3 nAChR in healthy subjects. In involved PPP skin there was a massive infiltration of granulocytes expressing ChAT and alpha-3 nAChR, and mast cells expressing AChE indicating a role for acetylcholine in inflammation. Cessation of smoking resulted in fewer pustules, and less scaling and erythema. The mechanisms for the effect of nicotine/smoking in PPP are still unknown but nicotine may lead to enhanced inflammation in consideration of the properties of the sweat duct and/or nicotine might facilitate autoimmune reactions.
