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Integumentary associations of pernicious anaemia

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Abstract

The integumentary associations of pernicious anaemia have been studied by comparison between a group of 125 patients with pernicious anaemia and a matched control group. The significant associations of pernicious anaemia are Sutton's (halo) naevus, vitiligo (particularly of late onset), premature and early greying of hair, blonde hair and blue eyes.

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... Vitiligo affects 0.14 to 3% of the world popula tion [1]. Several hypotheses were put forward to explain the depigmentation [2][3][4][5][6]. The presence of melanocytes in vitiligo skin of human beings is a matter of controversy [7][8][9][10][11][12][13][14][15]. ...
... 1. The activity of the enzyme was determined in absence of 2-amino-4-hydroxy-6, 7 -dimethyltetrahydropteridine (DHPH 4 ) which is an essential cofactor for tyrosine hydmxylase [20]. ...
... 3. 3-iodotyrosine (0.5 mM) which is a specific inhibitor of tyrosine hydroxylase [37) did not decrease the rate of dopa formation by the epidermal homogenates while phenylthiow-ea (1.0 mM) a specific inhibitor of tymsinase [38] completely inhibited the dopa formation by the epidermal homogenates. 4. That, what was measw-ed is tyrosinase is also shown by the experiments on 14 C(U)-L-Tyrosine incorporation into melanin. ...
... Vitiligo affects 0.14 to 3% of the world popula tion [1]. Several hypotheses were put forward to explain the depigmentation [2][3][4][5][6]. The presence of melanocytes in vitiligo skin of human beings is a matter of controversy [7][8][9][10][11][12][13][14][15]. ...
... 1. The activity of the enzyme was determined in absence of 2-amino-4-hydroxy-6, 7 -dimethyltetrahydropteridine (DHPH 4 ) which is an essential cofactor for tyrosine hydmxylase [20]. ...
... 3. 3-iodotyrosine (0.5 mM) which is a specific inhibitor of tyrosine hydroxylase [37) did not decrease the rate of dopa formation by the epidermal homogenates while phenylthiow-ea (1.0 mM) a specific inhibitor of tymsinase [38] completely inhibited the dopa formation by the epidermal homogenates. 4. That, what was measw-ed is tyrosinase is also shown by the experiments on 14 C(U)-L-Tyrosine incorporation into melanin. ...
... The association between premature greying and certain organ specific autoimmune diseases is well recognized. Autoimmunity has been proposed as the cause because of the higher frequency (about 50%) of greying in patients with pernicious anemia, a known autoimmune disease [16]. In a controlled study of 125 patients with pernicious anaemia, 11% had premature greying, defined as onset before the age of 20, compared with 2% in the control group [16]. ...
... Autoimmunity has been proposed as the cause because of the higher frequency (about 50%) of greying in patients with pernicious anemia, a known autoimmune disease [16]. In a controlled study of 125 patients with pernicious anaemia, 11% had premature greying, defined as onset before the age of 20, compared with 2% in the control group [16]. In a recent Latent class analysis of a series of 717 patients with NSV an early age onset (prepubertal onset) class vitiligo was significantly more associated with premature greying as compared to late age onset of vitiligo [17]. ...
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Hair goes grey with chronological aging. Premature hair greying may have significant adverse effects on the appearance, self-esteem, and socio-cultural acceptance of the affected individual. The exact aetiopathogenetic mechanism causing premature greying is still not clear and much speculative. Premature canities may appear alone as an autosomal dominant trait or it may occur in association with certain other disorders. The genes Pax3 and MITE play an important role in melanocyte stem cell maintenance and differentiation. Defective melanosomal transfer to the cortical keratinocytes or melanin incontinence due to melanocyte degeneration is also believed to contribute to greying. Despite the extensive molecular research being carried out to understand the pathogenesis of canities, treatment options still remain far from satisfactory and no effective therapy is available. Premature greying is a feature in a number of well recognised syndromes. A number of other conditions have also been observed to be associated with premature greying of hair.
... Several studies showed that vitiligo has been associated with autoimmune thyroid diseases, pernicious anemia, Addison's disease. [4][5][6][7][8] Also, in the present study, autoimmune thyroid diseases were found in 8.4% of the patients with generalized vitiligo, although no patients suffered from pernicious anemia or Addison's disease. This percentage is significantly higher than 1.90% frequency of autoimmune thyroid disease in the general United States population and is similar to 17.0% frequency among unselected white probands with vitiligo. ...
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We reviewed the causes of "loss of skin color" in 144 patients, who visited Vitiligo Clinic of Kyoto University Hospital between April 2005 and August 2008. The numbers of patients with generalized and segmental Vitiligo vulgaris were 98 (68.1%) and 26 (18.1%), respectively. Small numbers of the patients suffered from Vogt-Koyanagi-Harada disease, piebaldism, congenital albinism, Hypomelanosis of Ito, post-inflammatory hypopigmentation, white leaf-shaped macules associated with tuberous sclerosis and nevus hypopigmentosus. One forth of the patients with generalized vitiligo had complications, while no complications were found in the patients with segmental vitiligo. Among the complications, autoimmune diseases dominated 43% (10 of 23 cases). Autoimmune thyroid diseases explained for the most of the complicated autoimmune diseases and were associated with 7.4% of the patients with generalized vitiligo. Minor autoimmune complications include myasthenia gravis, Sjogren syndrome and autoimmune nephritis. Reflecting the condition that our clinic is located in a university hospital, vitiligo patients with end-stage non-melanoma cancers of internal organs accounted for 8.4% of the patients of generalized vitiligo.
... Vitiligo is frequently associated with other autoimmune disorders, particularly autoimmune thyroid disease (Boelaert et al., 2010; Ochi & DeGroot, 1969), autoimmune polyendocrine syndromes (Ahonen et al., 1990; Neufeld et al., 1990), pernicious anaemia (Dawber, 1970), Addison's disease (Zelissen et al., 1995), and alopecia areata (Ahmed et al., 2007). Furthermore, patients with vitiligo are more likely to suffer from autoimmune conditions than those in the general population (Birlea et al., 2008; Cunliffe et al., 1968; Liu et al., 2005; Turnbridge et al., 1977). ...
... [14,15] Fifty-five percent of patients with pernicious anemia were found to develop graying of hair before 50 years, as compared to only 30% in the control group. [16] Reversible hypopigmentation of hair has also been noted in association with nutritional deficiencies like chronic protein loss (due to kwashiorkor, nephrosis, celiac disease, and other causes of malabsorption), severe iron deficiency and copper deficiency. [14] Serum copper was significantly lower in 66 patients with premature canities, as compared to normal controls (66) in one study. ...
Article
Premature graying is an important cause of low self-esteem, often interfering with socio-cultural adjustment. The onset and progression of graying or canities correlate very closely with chronological aging, and occur in varying degrees in all individuals eventually, regardless of gender or race. Premature canities may occur alone as an autosomal dominant condition or in association with various autoimmune or premature aging syndromes. It needs to be differentiated from various genetic hypomelanotic hair disorders. Reduction in melanogenically active melanocytes in the hair bulb of gray anagen hair follicles with resultant pigment loss is central to the pathogenesis of graying. Defective melanosomal transfers to cortical keratinocytes and melanin incontinence due to melanocyte degeneration are also believed to contribute to this. The white color of canities is an optical effect; the reflection of incident light masks the intrinsic pale yellow color of hair keratin. Full range of color from normal to white can be seen both along individual hair and from hair to hair, and admixture of pigmented and white hair is believed to give the appearance of gray. Graying of hair is usually progressive and permanent, but there are occasional reports of spontaneous repigmentation of gray hair. Studies evaluating the association of canities with osteopenia and cardiovascular disease have revealed mixed results. Despite the extensive molecular research being carried out to understand the pathogenesis of canities, there is paucity of effective evidence-based treatment options. Reports of repigmentation of previously white hair following certain inflammatory processes and use of drugs have suggested the possibility of cytokine-induced recruitment of outer sheath melanocytes to the hair bulb and rekindled the hope for finding an effective drug for treatment of premature canities. In the end, camouflage techniques using hair colorants are outlined.
... One study has shown that 55 per cent of patients with pernicious anaemia were found to develop greying hair before 50 years old as compared with only 30 per cent in the control group. 12 Reversible hypopigmentation of hair has also been noted in association with nutritional deficiencies, such as chronic protein loss (due to kwashiorkor, nephrosis, celiac disease and other causes of malabsorption), severe iron deficiency and copper deficiency. It has also been hypothesised that premature hair greying is associated with osteopenia. ...
Article
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Objective: There is evidence for a strong correlation between low bone mineral density and hearing loss. Furthermore, premature hair greying has been associated with low bone mineral density. Hence, this study aimed to investigate, for the first time, the relationship between premature hair greying and hearing impairment. Methods: Fifty patients with premature hair greying (20 women and 30 men), aged under 40 years (mean, 30.1 ± 4.9 years), who had onset of hair greying in their twenties, were recruited, along with 45 age- and sex-matched healthy control subjects (17 women and 28 men; mean age, 28.7 ± 5.1 years). Each participant was tested with low frequency audiometry at 0.125 to 2 kHz, high frequency audiometry at 4 to 8 kHz, and extended high frequency audiometry at 9 to 20 kHz. Results: Hearing thresholds were similar at all frequencies from 0.25 to 4 kHz (p > 0.05); however, significant hearing loss was observed at all frequencies from 8 to 20 kHz in the premature hair greying group compared with the control group (p < 0.05). Conclusion: Patients with premature hair greying had hearing impairment at extended high frequencies. Premature hair greying may be an important risk factor for hearing loss.
... In addition to these reasons, factors such as B12 deficiency, some chemotherapeutic drugs, cholesterol, imbalanced and malnutrition or smoking are thought to cause PHG. [27][28][29][30] Various studies have been carried out in order to determine the mechanism of graying of hair and its main causes. One of these is the study directed by Han J. et al. [31] in 2008 to determine the hair color gene. ...
Article
Full-text available
Hair graying is known as a natural part of the aging process. This aging process occurs with the graying of half of the hair at the age of 50 on average. There is another process that happens outside this natural process. The graying process that starts under the age of 20 on average is called Premature hair graying (PHG). There are many genetic and environmental factors that affect the graying process. In this review prepared, IRF4 (Interferon regulatory factor 4) gene, which is one of these factors and has many functions in the body, is focused on. In addition, other factors were also mentioned, and many studies carried out for hair repigmentation, which has the characteristics of treatment, were examined, and the obtained findings were shared.
... The image that arises from the current research indicates multifactorial background of hair greying with a wide range of different factors, different mechanisms and molecular pathways included [5,9]. Hair greying comes along with many diseases including among others Waardenburg syndrome, spastic paraplegia, pernicious anemia and progeria (Hutchinson-Gilford and Werner syndrome) [25][26][27][28]. The genetic predisposition to the development of premature greying of hair has been recognized only to a very limited extent. ...
Article
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Background: Greying of the hair is an obvious sign of human aging. In addition to age, sex- and ancestry-specific patterns of hair greying are also observed and the progression of greying may be affected by environmental factors. However, little is known about the genetic control of this process. This study aimed to assess the potential of genetic data to predict hair greying in a population of nearly 1000 individuals from Poland. Results: The study involved whole-exome sequencing followed by targeted analysis of 378 exome-wide and literature-based selected SNPs. For the selection of predictors, the minimum redundancy maximum relevance (mRMRe) method was used, and then two prediction models were developed. The models included age, sex and 13 unique SNPs. Two SNPs of the highest mRMRe score included whole-exome identified KIF1A rs59733750 and previously linked with hair loss FGF5 rs7680591. The model for greying vs. no greying prediction achieved accuracy of cross-validated AUC = 0.873. In the 3-grade classification cross-validated AUC equalled 0.864 for no greying, 0.791 for mild greying and 0.875 for severe greying. Although these values present fairly accurate prediction, most of the prediction information was brought by age alone. Genetic variants explained < 10% of hair greying variation and the impact of particular SNPs on prediction accuracy was found to be small. Conclusions: The rate of changes in human progressive traits shows inter-individual variation, therefore they are perceived as biomarkers of the biological age of the organism. The knowledge on the mechanisms underlying phenotypic aging can be of special interest to the medicine, cosmetics industry and forensics. Our study improves the knowledge on the genetics underlying hair greying processes, presents prototype models for prediction and proves hair greying being genetically a very complex trait. Finally, we propose a four-step approach based on genetic and epigenetic data analysis allowing for i) sex determination; ii) genetic ancestry inference; iii) greying-associated SNPs assignment and iv) epigenetic age estimation, all needed for a final prediction of greying.
... Besides the abovementioned involvement of the immune system in vitiligo pathogenesis, epidemiological evidence further corroborates the autoimmune genesis of vitiligo. In particular, vitiligo is present within the autoimmune polyendocrine syndromes (51), and it is more frequently encountered in family members of patients affected by autoimmune diseases, such as inflammatory bowel disease, psoriasis, rheumatoid arthritis, type 1 diabetes, systemic lupus erythematosus, pernicious anemia, and AITD (31,(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68)(69). The latter, as outlined in several studies performed over the last decades, represent the most frequent autoimmune disorders associated with vitiligo (54,58,(66)(67)(68)(69)(70)(71)(72)(73). ...
Article
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Vitiligo represents the most common cause of acquired skin, hair, and oral depigmentation, affecting 0.5–1% of the population worldwide. It is clinically characterized by the appearance of disfiguring circumscribed skin macules following melanocyte destruction by autoreactive cytotoxic T lymphocytes. Patients affected by vitiligo usually show a poorer quality of life and are more likely to suffer from depressive symptoms, particularly evident in dark-skinned individuals. Although vitiligo is a non-fatal disease, exposure of affected skin to UV light increases the chance of skin irritation and predisposes to skin cancer. In addition, vitiligo has been associated with other rare systemic disorders due to the presence of melanocytes in other body districts, such as in eyes, auditory, nervous, and cardiac tissues, where melanocytes are thought to have roles different from that played in the skin. Several pathogenetic models have been proposed to explain vitiligo onset and progression, but clinical and experimental findings point mainly to the autoimmune hypothesis as the most qualified one. In this context, it is of relevance the strong association of vitiligo with other autoimmune diseases, in particular with autoimmune thyroid disorders, such as Hashimoto thyroiditis and Graves’ disease. In this review, after a brief overview of vitiligo and its pathogenesis, we will describe the clinical association between vitiligo and autoimmune thyroid disorders and discuss the possible underlying molecular mechanism(s).
Article
Background Premature canities is a common yet unfathomed disorder. The evidence for the role of micronutrient deficiency in premature canities is not well established. Aim The present study was undertaken to evaluate the micronutrient levels in Indian patients with premature canities as compared to controls. Materials and Methods We conducted a case–control study in 52 self-reporting patients with premature canities (<20 years age). Micronutrient levels including serum Vitamin B12, biotin, and folic acid were assessed and compared among the patients and controls. Results We observed that mean serum Vitamin B12 (198.07 ± 88.98 pg/ml in cases vs. 343.07 ± 143.06 pg/ml in controls, P = 0.000), folic acid (6.22 ± 2.46 ng/ml in cases vs. 8.49 ± 4.18 ng/ml in controls, P = 0.01), and biotin (252.71 ± 18.79 pg/ml in cases vs. 266.47 ± 30.44 pg/ml in controls, P = 0.013) levels were significantly lower in cases as compared to the controls. Conclusion In view of the dark hair and many prevailing myths, premature canities is a significant problem in Asians with profound psychosocial impact. This study unveils the association with Vitamin B12, folic acid, and biotin deficiencies. Larger studies are recommended to arrive on a logical conclusion.
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Vitiligo, the most common cutaneous depigmentation disorder, has reported associations with other autoimmune diseases. However, literature on the strengths of the associations is conflicting, and no data on the subject exist from a Canadian population. To determine autoimmune disease associations with vitiligo and which, if any, screening bloodwork is appropriate in vitiligo patients. A retrospective review of vitiligo patients admitted to the Toronto Western Hospital phototherapy unit was conducted from January 1, 2000, to August 30, 2009. Data regarding patient characteristics, vitiligo clinical features (family history, age at onset, type, extent), associated diseases in the patient and family, and admission bloodwork (hemoglobin, vitamin B12, thyroid-stimulating hormone [TSH], antinuclear antibody) were recorded and compared, using the Fisher exact test where applicable. A total of 300 patient charts were reviewed (average age 41.5 ± 15.5 years; 47% male, 53% female). Hypothyroidism was present in 12.0% and pernicious anemia in 1.3% of patients-significant increases over the population prevalence. No other differences in prevalence were seen compared to the general population. TSH was increased in 3.7% of patients without a history of hypothyroidism. Hemoglobin and vitamin B12 were decreased in 0.3% of vitiligo patients without a history of pernicious anemia. We found a significantly higher prevalence of hypothyroidism and pernicious anemia in vitiligo patients.
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A second patient with hypertrophic protein-losing gastropathy and extensive vitiligo was studied. Upper gastrointestinal radiographs and endoscopy revealed multiple polyps of the upper half of the stomach. The patient was achlorhydric to pentagastrin stimulation. Clearance of51Cr-labeled protein by the gastrointestinal tract was about 15 times normal. A total gastrectomy was done for relief of persistent epigastric pain and correction of hypoproteinemia. Histologically the polyps consisted of hypertrophied mucosal glands with cystic dilatation deep to the glandular layer. The similarity of this patient to a patient previously seen at our hospital led us to report the possible association of hypertrophic protein-losing gastropathy with vitiligo.
Chapter
Large-scale epidemiological surveys have shown that most cases of vitiligo occur sporadically, though about 15–20% of patients report one or more affected relatives. The rationale for genetic studies of vitiligo susceptibility is that underlying genes are involved in mediating disease causation, either increasing or decreasing risk (protective). Three different general approaches have been used to identify genes that mediate vitiligo susceptibility: the candidate gene approach, the genome-wide approach, and the gene expression approach. Extensive experience has proven that the only analytic approach that produces verified discovery of bona fide disease genes is the genome-wide approach. Retrospective analyses of candidate gene studies have shown that the vast majority of claimed candidate gene associations represent false-positives. Accordingly, the candidate gene approach is no longer considered valid for de novo disease gene discovery and is reserved for confirmatory studies only. Similarly, almost all genes that exhibit major expression differences between disease and non-disease states turn out to not correspond to causal genes, but instead represent secondary effects, and thus likewise gene expression studies have generally not led to the discovery of genes that are causal for complex diseases. Indeed, none of the genes initially suggested on the basis of the expression approach now appear to be involved in vitiligo causation at all. In contrast, genome-wide genetic analyses, particularly genome-wide association studies (GWAS), have proven a remarkably robust approach to disease gene discovery, yielding findings that are highly reproducible and which, in aggregate, have provided dramatic advances in understanding the biological basis of many different complex diseases, including vitiligo. Reported candidate gene associations and expression difference findings that are not observed in well-powered GWAS of the same population are not now considered to be valid indications of disease-causal genes and thus will not be discussed here.
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Generalized vitiligo is an autoimmune disease of skin pigmentation that is associated with increased prevalence of other autoimmune diseases, particularly autoimmune thyroid disease (AITD; principally Hashimoto's disease and Graves' disease), both in vitiligo patients and their close relatives, suggesting a heritable predisposition involving, in part, shared susceptibility genes. This review summarizes current knowledge of vitiligo epidemiology and genetics, highlighting recent findings from genome-wide approaches to disease gene identification, emphasizing susceptibility loci shared with other autoimmune diseases, particularly AITD, as well as some important differences. Inherited susceptibility to generalized vitiligo involves a number of specific genes, many of which are shared with other autoimmune diseases that are epidemiologically associated with vitiligo, including AITD, confirming a longstanding hypothesis about the genetic basis of these disorders. These genes provide potential therapeutic targets for novel approaches to treatment as well as for approaches to presymptomatic diagnosis and disease prevention in individuals with inherited susceptibility to this group of autoimmune diseases.
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Vitiligo is a common skin and hair depigmentary disorder that results from selective destruction of melanocytes. It occurs in a typical multifactorial, polygenic inheritance. Several studies have indicated that vitiligo is associated with some autoimmune diseases. In this paper we examined 6,516 vitiligo patients including clinical characteristics, familial involvement, and their association with other autoimmune diseases. Compared with sporadic vitiligo probands, familial vitiligo probands have earlier age onset and longer disease duration. The prevalences of four autoimmune diseases namely rheumatoid arthritis, chronic urticaria, alopecia areata and psoriasis, were significantly elevated in generalized vitiligo probands and their first-degree relatives. The prevalences of chronic urticaria, rheumatoid arthritis, psoriasis were much higher in familial generalized vitiligo probands. In addition, the prevalences of diabetes mellitus and asthma were also higher in familial vitiligo probands. These findings indicate that generalized vitiligo may share common genetic aetiologic links with other autoimmune diseases, and the genetic component of familial generalized vitiligo is stronger.
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Several variants of generalised vitiligo can be recognised by their cutaneous distribution. In some, certain anatomical regions--e.g., hands--are predominantly affected while the cutaneous depigmentation in other variants shows a similar anatomical distribution to that of the internal structures affected in some of the autoimmune and rheumatic diseases. Five patients have been seen, and three described by others, with vitiligo affecting skin of eyelids and lower front of neck, reminiscent of the anatomical distribution of lesions in thyrotoxicosis with exophthalmos: two of these patients have thyrotoxicosis. Another variant of vitiligo mimicks the anatomical distribution of lesions in ankylosing spondylitis, Reiter's syndrome, and ulcerative colitis and there are cases simulating lupus erythematosus, rheumatoid arthritis, and psoriasis. It is suggested that the parts of the body affected in each vitiligo variant and its corresponding internal disease constitute a set os mosiac patches with distinctive shared characters. These may have morphogenetic functions during embryonic development and be potentially autoantigenic later in life.
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Six of 20 patients with extensive vitiligo treated with ACTH experienced repigmentation at the end of 15 weeks. However, depigmentation recurred when the treatment was stopped.
Chapter
Anatomy and physiologyAlopeciaAbnormalities of hair shaftExcessive growth of hairHair pigmentationHair cosmetics
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Vitiligo, a disorder characterized by the destruction of melanocytes, is often associated with diseases in which there are increased frequencies of autoantibodies. For this reason we investigated two patients with vitiligo, alopecia universalis, mucocutaneous candidiasis, and multiple endocrine insufficiencies for antibodies to melanin-producing cells. Using direct immunofluorescence of normal and vitiliginous skin from both patients and indirect immunofluorescence with both patients' serum, we could not detect these antibodies. However, an immunofluorescent complement-fixation test demonstrated a circulating antibody that bound to melanocytes in human skin, nevus cells and melanoma cells. Specificity of cellular fluorescence for nevus and melanoma cells was shown on serial sections stained with hematoxylin and eosin and was inferred for melanocytes from their distribution in human skin and their presence when the normal but not vitiliginous skin of both patients was used as substrate. This antibody was characterized as an IgG that activated complement via the classical pathway.
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Local injection of physostigmine revealed that dermatomally distributed vitiligo was associated with a dysfunction of the sympathetic nerves in the affected skin and that non-dermatomally distributed vitiligo was not. These observations led to the hypothesis that the primary disturbance of dermatomally distributed vitiligo lies in the sympathetic nerves of the affected area and that non-dermatomally distributed vitiligo has its primary disturbance in the melanocyte itself, where an autoimmune mechanism is suspect. Results of therapy supported this hypothesis by showing that topical corticosteroid is effective only in the latter, while the former reacts to oral nialamide. It is proposed that non-dermatomally distributed vitiligo be referred to as Type A and dermatomally distributed vitiligo as Type B.
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The treatment of vitiligo has been unsatisfactory. Introduction of systemic furocoumarins to treatment regimens has given very promising results. Trimethylpsoralen has been found to be more potent than 8-methoxypsoralen. In cases studied, ultraviolet irradiation of affected sites following topical application of trimethylpsoralen was found to hasten the process of repigmentation. Simultaneous treatment of underlying disease produced a quicker response followed by sustained relief.
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The association between skin changes and a definite diet was made long before the modern development of nutritional science: James Lind (1716–1794) advocated the use of lemon and orange juice for the prevention and treatment of scurvy, which was suggested to occur in laborers.1 Malnutrition usually is thought to be confined to underdeveloped areas; however, it is a worldwide problem including vitamin deficiencies in industrial countries where alcoholism can be found. Kwashiorkor was first described only 50 years ago by Williams.2 Mild and subclinical nutrition deficiencies may be caused by any abnormal condition that increases the need of nutritional factors (ie, fever), interferes with the absorption or utilization of it, and causes its elimination too rapidly, in addition to subnormal intake.3Pigmentary changes seen in the skin due to malnutrition usually result in hyperpigmentation, sometimes in hypopigmentation or reticulated or poikilodermatous discoloration. The pattern may be that of chloasma with symmetric patches on the cheeks and forehead; it may be lesional, confined to eczematous areas showing a purplish brown “pellagroid” discoloration; it may also present as generalized melanosis, resembling Addison's disease. The mechanism of melanosis is obscure and might be due to amino acid imbalance in malabsorption.4 Another way of pathogenesis of hyperpigmentation may be through photosensitization or thickening of the horny layer in ichthyosiform reaction. Discoloration may also be due to cutaneous losses of nutrients through sweat glands, sebaceous glands, and hair follicles and through epidermal desquamation.5 No abnormality of adrenocortical function was found in cases of undernutrition or in cases of cachexia with pigmentation.6
Article
Four hundred and eighty one cases of vitiligo (acquired idiopathic depigmentation) were studied clinically. They were divided into two types, type B, in which depigmented patches are confined to a definite dermatome in the same manner as herpes zoster, and type A, which included all cases of vitiligo not classified as type B. The ratio of type A:type B was approximately 3:I. Onset of type A vitiligo could occur at any age, whereas type B generally affected the young. The activity of type B vitiligo usually ceased after one year, following rapid spread over the particular dermatomal area. However, in type A vitiligo new depigmented patches continued to appear throughout the patients' lives. Association with halo naevus and Köbner's phenomenon were observed exclusively in type A. Association with diseases with a proven or suggested allergic or immunological aetiology was more often found in type A. These findings support our hypothesis that type A and type B vitiligo have a different pathogenesis and that autoimmune mechanisms play a role only in type A.
Article
From an analysis of the clinical features of vitiligo and of the chemicals that cause depigmentation, a melanocyte self-destruct hypothesis for the etiology of vitiligo and graying of hair can be derived. A melanin precursor, one that is either a phenol or a catechol derivative or the phenol-tyrosinase complex, is lethal for melanocytes. When the natural mechanism that protects against the precursor is lost, the melanocytes are destroyed.
Article
Vitiligo, a common skin condition, has been reported in association with thyroid disease, pernicious anaemia, carcinoma of the stomach, Addison's disease and diabetes mellitus.Some subjects with vitiligo can be shown to possess circulating antibodies to thyroid gland, thyroglobulin, gastric parietal cells and adrenal gland, even in the absence of disease.Vitiligo is evidently another ‘skin-marker of internal disease’.
Article
Tyrosinase activity (Monophenol, dihydroxyphenylalanine: oxygen oxidoreductase EC 1.14.18.1) in vitiligo and normal epidermal homogenates of skin from human beings was measured by estimating β 3,4-dihydroxyphenylalanine (dopa) by a highly sensitive fluorometric method described in this paper. The tyrosinase activity in the vitiligo skin was about 4 to 37% of corresponding normal skin. The activity of tyrosinase in normal human skin from different individuals and from different regions of the body was in the range of 4 to 140 picomoles of β 3,4-dihydroxyphenylalanine formed per min/mg protein of epidermal homogenate. The enzyme from vitiligo and normal skin was severely inhibited by substance(s) of low molecular weight. The enzyme exhibits a lag of about 4 hr in the absence of added β 3,4-dihydroxyphenylalanine and 1 hr in presence of 5 μM dopa. Tyrosinase from the normal and vitiligo skin was inhibited by excess concentration of tyrosine. The homogenates from vitiligo skin could synthesize melanin from C¹⁴(U)-L-Tyrosine. The rate of tyrosine incorporation into melanin by the epidermal homogenates is increased by 3,4-dihydroxyphenylalanine (dopa) disproportionate to its effect on tyrosinase activity. Based on the data presented in this paper it is concluded that melanocytes are present in the vitiligo skin. A tentative hypothesis is put forward to explain the lack of melanin synthesis by the vitiligo skin under in vivo conditions, although melanocytes are present.
Article
Four patients with co-existing vitiligo and morphoea are reported. The significance of this association is discussed.
Chapter
Het vroegtijdig grijs worden is een relatief weinig frequent voorkomende afwijking van de menselijke beharing. Deze valt uiteraard het meest op bij het behaarde hoofd.
Article
Although the exact aetiology of vitiligo remains unclear, vitiligo is widely considered to have an autoimmune component in its pathogenesis based on disease associations. According to ethnic background, large variations exist in association with autoinflamma-tory/autoimmune disorders. Some reported associations may reflect a simple coexistence of two disorders, and the repertoire of associations may help to detect shared heritable predispositions for inflamma-tion and autoimmunity. Thyroid disorders are the most commonly associated to vitiligo in Caucasian populations, alopecia areata in Chinese populations, rheumatoid arthritis (RA) being more rarely associated in both.
Chapter
Kwashiorkor is a result of dietary deficiency of protein in the weaning and early postweaning stage of childhood. In underdeveloped nations it remains a significant cause of death among children from one to four years of age.
Chapter
This is a rather common disorder affecting all races.
Chapter
The term “leukoderma acquisitum centrifugum” is a somewhat generic one commonly used synonymously with “halo nevus” but applicable to various tumors, including primary or secondary melanomas, surrounded by leukoderma (Table 119). This entity has been described as “leukopigmentary nevus” [2], “perinevoid vitiligo” [3], and “perinevoid leukoderma” [4]. While leukoderma acquisitum centrifugum applies to all nevi surrounded by a macule of leukoderma, the term “halo nevus” is restricted to nevus cell nevus.
Chapter
One purpose of any classification is to categorize, organize, and increase understanding of the disorders classified. For hereditary leukodermas, the presence or absence of certain common features permits a useful subclassification (see Table 13, page 60). Those disorders with features of oculocutaneous albinism (3+ hypomelanosis) must be distinguished from those having a relative (1 or 2+ hypomelanosis) generalized pigmentary dilution. In the latter, the hypomelanosis may be apparent only in comparison to family members or individuals of the same ethnic background, and these are readily distinguished from entities usually featuring circumscribed hypomelanosis. The fourth category involves hereditary disorders in which pigmentation of the hair but not of the skin is affected.
Article
Background: Vitiligo has been associated with various disorders including pernicious anemia, diabetes, hyperthyroidism, hypothyroidism, alopecia areata, Addison's disease, and so on. Autoantibodies against specific organs are also frequently found. However, the positive rates of these autoantibodies' detection by various reporters showed too much diversity to extrapolate a definitive conclusion. Objective: The purpose of this study was to investigate the autoimmune aspects of vitiligo by evaluating the detection rates of various organ-specific autoantibodies. Methods: We classified vitiligo patients into 2 groups(autoantibody positive group and autoantibody negative group) and 3 types(localized, generalized, and universalis). The overall detection rates of various autoimmune and endocrine diseases were also assessed in patients and the control, which was composed of 40 young healthy volunteers. Results: 1. There were 106 males(33.0%) and 215 females(67.0%) in total 321 vitiligo patients. 2. 115 patients(35.8%) were determined to be autoanitibody positive, and 206 patients(64.2%) were negative. 3. The most frequent type of vitiligo was generalized type in both autoantibody positive and negative group. 4. Mean age of onset was 30.8 years. And there was a statistically significant difference between autoantibody positive(37.6 years) and negative(29.3 years) group(p < 0.05). 5. Average disease duration was 6.5 years in autoantibody positive group and 4.3 years in autoantibody negative group. 6. The positive rates of anti-nuclear, anti-microsomal, anti-smooth muscle antibody, and rheumatoid factor showed no significant differences between vitiligo patients and normal control group(p > 0.05). But the positive rate of antithyroid antibody was significantly higher in vitiligo patients than in normal control(κ 2 = 4.234, p = 0.040). 7. The prevalence rates of autoimmune & endocrine disorders showed no significant differences between vitiligo patients and normal control(p > 0.05). 8. The prevalence rates of autoimmune and endocrine disorders were higher in autoantibody positive vitiligo group(33.0%) than in negative group(29.6%), although it was not statistically significant(p > 0.05). However, the prevalence rate of thyroid disease itself was significantly higher in autoantibody positive group than in negative group(p = 0.004). 9. Treatment response to PUVA therapy was better in autoantibody positive group than in negative group(p = 0.0003). Conclusion: With these results, we were able to conclude that anti-thyroglobulin antibody is more frequently found in vitiligo patients than in normal control. And autoantibody positive vitiligo patients showed higher prevalence rate of thyroid disease and better treatment response to PUVA therapy than in autoantibody negative vitiligo patients. Therefore, the presence of autoantibody in vitiligo patients seems to be related with a better treatment response for PUVA therapy.
Article
Vitiligo is a common skin disorder characterised by the presence of depigmented macules resulting from the destruction of cutaneous melanocytes. Autoimmunity is an important hypothesis with regard to vitiligo aetiology and pathogenesis and, in this review, the evidence for autoimmune responses being involved in the development of vitiligo willbe discussed. Particularly relevant are autoantibodies and autoreactive T cells in vitiligo patients that have cytotoxic effects upon pigment cells. Furthermore, predisposition to vitiligo appears to be associated with certain alleles of the major histocompatibility complex class II antigens as well as with genetic variants in other autommune-susceptibility genes. Moreover, the association of vitiligo with autoimmune disorders, animal models of the disease, and the positive response to immunosuppressive therapeutic agents emphasise the potential role of autoimmunity in the development of this disorder.
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Alopecia AreataHeterochromia IridesSenile CanitiesSudden Whitening of Hair
Article
Background: The significance of associated autoimmune/autoinflammatory diseases in generalized vitiligo patients with respect to their clinical profile has not yet been completely established. Objective: The objective of this study was to evaluate the clinical significance of associated autoimmune/autoinflammatory diseases in generalized vitiligo patients with respect to some general clinical variables, distribution pattern, disease activity and treatment response. Methods: Seven hundred generalized vitiligo patients were included in this retrospective observational cohort study. Results: Associated autoimmune/autoinflammatory diseases were present in 15.4% of the patient population and were more common in women compared to men, especially concerning thyroid disease. Only vitiligo patients with thyroid disease had clear different clinical characteristics. The percentage of total body surface area involvement was significantly (P = 0.005) higher in the presence of thyroid disease which was more pronounced in women compared to men. Patients with thyroid disease had a particular predisposition to acral and joint depigmentations. No cleardifferences in disease activity or response to therapy were observed in vitiligo patients with or without autoimmune/autoinflammatory disorders. Conclusion: The presence of associated autoimmune/autoinflammatory diseases seems to influence the clinical profile of generalized vitiligo patients. Our results support the hypothesis that in the presence of a thyroid disorder, the disease activity of vitiligo is more extensive, in particular on areas prone to friction.
Chapter
A wide spectrum of systemic and organic diseases may cause disturbances in hair growth. Therefore, changes of hair growth have always been regarded either as an indication of disorders of other organs or as a confirmation of such disorders (Comaish 1979; Rook and Dawber 1982). However, only after extended research on the mechanisms regulating hair growth have their dependence on the correct functioning of other organ systems been better understood.
Article
Background: Few large-scale studies have quantified the burden of comorbid autoimmune diseases in patients with vitiligo. Objective: We sought to determine the prevalence of comorbid autoimmune diseases in patients with vitiligo. Methods: We conducted a manual chart review on a cohort of 1873 patients with vitiligo seen between January 2002 and October 2012 at the Henry Ford Health System in Detroit, MI. Patients were excluded if they had fewer than 2 dermatology notes (N = 595) or if they were never given a diagnosis of vitiligo by a dermatologist (N = 180). Results: Of 1098 patients with vitiligo, nearly 20% had at least 1 comorbid autoimmune disease. Compared with the general US population, we found a higher prevalence of thyroid disease (12.9%, P < .001), alopecia areata (3.8%, P < .001), inflammatory bowel disease (0.9%, P = .046), pernicious anemia (0.5%, P = .007), systemic lupus erythematosus (0.3%, P = .048), Guillain-Barre syndrome (0.3%, P < .001), discoid lupus (0.2%, P = .003), linear morphea (0.2%, P < .001), myasthenia gravis (0.2%, P = .002), and Sjögren syndrome (0.2%, P = .011). Limitations: The study lacked a control group. This was a single-institution study with possible selection bias, and thus the findings may not be representative of the overall population of patients with vitiligo. Conclusions: We observed a high prevalence of comorbid autoimmune diseases in patients with vitiligo and report several new associations.
Article
Generalized vitiligo is an acquired disorder in which patches of depigmented skin, overlying hair, and oral mucosa result from progressive autoimmune loss of melanocytes from the involved areas. Although vitiligo is perhaps the most common pigmentary disorder, insufficiently clear clinical definition of the disorder and lack of a good laboratory animal model have inhibited progress in understanding its pathobiology, its environmental triggers, and in developing specific and effective therapeutic approaches. Vitiligo results from a complex interaction of environmental, genetic, and immunologic factors, which ultimately contribute to melanocyte destruction, resulting in the characteristic depigmented lesions. In the past few years, studies of the genetic epidemiology of generalized vitiligo have led to the recognition that vitiligo is part of a broader, genetically-determined, autoimmune/autoinflammatory diathesis. Attempts to identify genes involved in vitiligo susceptibility have involved both allelic association studies of candidate genes and genome-wide linkage analyses to discover new genes, and these studies have begun to shed light on the mechanisms of vitiligo pathogenesis. It is anticipated that the discovery of biological pathways of vitiligo pathogenesis will provide novel therapeutic and prophylactic targets for future approaches to the treatment and prevention of vitiligo and its associated autoimmune diseases.
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Technological and theoretical advances enabled by the human genome project have led to efforts to map and identify specific genes involved in vitiligo susceptibility. Specific approaches include the Candidate Gene Approach, the Genome-Wide Approach, and the Gene Expression Approach, each offering specific advantages and disadvantages. Generalized vitiligo is epidemiologically associated with a number of autoimmune diseases. This epidemiologic association has a genetic basis, at least in part, as vitiligo patients' close relatives have elevated risk of both vitiligo and other autoimmune diseases, even if those relatives don't have vitiligo. Several generalized vitiligo susceptibility genes have now been identified, including loci in the MHC, PTPN22, and NALP1. The status of other genes, whose involvement has been suggested, remains uncertain.
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Hair is a defining feature of mammals. In other species hair confers important functions that affect survival. Most have been lost or are irrelevant in humans but the role of hair in social and sexual signalling in women and in men survives and thrives. Departures from cultural norms, either physiological or due to pathology, can therefore cause much concern and anxiety. Following an introduction to hair biology, this chapter considers the approach to the diagnosis and management of the patient with hair loss before discussing specific hair disorders. These include the various forms of hair loss due to hair follicle pathology, disturbances in hair cycling and hair shaft dystrophies, and disorders associated with excessive hair growth. The chapter concludes with a discussion of acquired alterations in hair pigmentation.
Article
Full-text available
We report a case of dermatitis herpetiformis co-localised with segmental vitiligo in a 37-year-old woman with a background history of autoimmune polyglandular syndrome type 2. We propose genetic mosaicism as a possible mechanism. There has only been one previous case report in which dermatitis hepetiformis co-localised in close proximity but not exclusively within vilitigo in a patient with autoimmune thyroiditis. To our knowledge, this is the first case report of dermatitis herpetiformis co-localised exclusively to segmental vitiligo in the presence of autoimmune polyglandular syndrome.
Article
Premature graying of hair (PGH) is defined as graying of hair before the age of 20 years in Caucasians and before 30 years in African American population. It can severely affect the self-esteem of an individual. The exact etiopathogenesis remains unknown, although it has been associated with premature aging disorders, atopy, and autoimmune diseases. Patients, who present with PGH, should be assessed for syndromes and metabolism diseases. Hair dyes remain the main modality of the treatment for cosmetic concerns after nutritional supplementation.
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Diagnostic Principles and Applications Robert B. Taylor, MD This book is intended to make you a better clinician, as you learn some unfamiliar, perhaps even forgotten, pathways to important diagnostic destinations. If this book were a road map, it would be about the “blue highways”--the less-traveled roads, the ones that may become vital when the "red line" major highways don't get you where you need to go. Think about the observation by American laryngologist Chevalier Jackson cited above: When presented with a wheezing patient, an experienced clinician would consider asthma to top the list of diagnostic considerations. But, in certain clinical contexts, the astute clinician might also think of foreign body aspiration, Wegener granulomatosis, parasitic infection, or airway constriction by an aortic aneurysm. Considering these other possibilities is the first step in making the correct diagnosis. Thus, this is not a typical, “comprehensive” differential diagnosis book, with long lists of diseases, most familiar to practicing clinicians, that might explain a symptom, sign, or abnormal laboratory finding. Instead I offer selected topics, the uncommon—and sometimes exasperatingly esoteric—disease causes we sometimes fail to consider. As an analogy, I offer the Lifeguard Paradox: If aspiring lifeguards were to spend the bulk of training time practicing what they will do most of the day at work, they would focus on learning to apply sunscreen to their own bodies. But in lifeguarding, unanticipated events happen, and the lifeguard must know how to handle them. In medicine, uncommon diseases and unlikely manifestations of common diseases occur with sometimes-surprising frequency, and we need to review them from time to time. Of course, clinicians also encounter the some diseases—whether everyday or rare--that we especially do not want to overlook, such as toxic megacolon and testicular torsion; when one of these appears in the coming pages it is tagged as a must-not-miss diagnosis. In this book, the emphasis is on the enlightened uses of traditional diagnostic tools—clinical history, physical examination, and basic laboratory tests and imaging. The more esoteric investigative methods—PET scans and genetic testing--seem to evolve constantly, and are best studied in journal and web-based sources that are more timely than books. Because the content of this book is selective, rather than attempting to be all-inclusive, I have tilted my choices toward identification of high-impact diseases. And also because this is a diagnosis book, I have included information about therapy only when I believed it would enrich the discussion or when I wanted to emphasize the urgency of reaching a timely, precise diagnostic end-point. What will you find in this book? I have included the following categories of diagnostic facts: Classical diagnostic pearls: For example, the patient with acute pericarditis often leans forward to relieve the anterior chest pain. Red flag symptoms and signs of serious illness: A salty taste when kissing an infant may represent the first clue to a diagnosis of cystic fibrosis. Counterintuitive clinical manifestations: The patient with gout may have a normal or low serum uric acid level during the acute attack; and nocturnal back pain has, in fact, not been found to be a useful indicator for serious spinal pathology. Bellwether signs and symptoms allowing an occasional early diagnosis: Abdominal distension is a common early manifestation of ovarian cancer; and patients with gastric cancer sometimes lose their appetite for meat early in the course of the disease. Curious clinical manifestations that may point to specific diagnoses: Here I think of the aquagenic pruritus of polycythemia vera, with itching that is aggravated by a hot shower. And the cutaneous “wake sign,” skin lesions resembling the wake left by a moving ship, has been described as seen only with scabies. Who needs this book? As medicine has become increasingly specialized, medical books have become correspondingly limited in their scope. This book, on the other hand, casts a very wide net, presenting diagnostic facts related to all ages and body systems. Thus, intended readers include medical students, residents, and practicing physicians, nurse practitioners, physician assistants, nurses and, in fact, anyone involved in making diagnostic observations and decisions. Do YOU need this book? Let’s see. If you see real, live patients in any specialty setting and cannot answer the following are five questions, I suggest that you put Diagnostic Principles and Applications high on your reading list: 1. What are the three characteristics of the scenario in which a diagnosis of breast cancer is often missed? 2. Of all the sites of possible lymphadenopathy, which is the most worrisome? 3. Low back pain that improves with forward flexion of the spine suggests what diagnosis? 4. Hyponatremia may be the clue to what psychiatric disorder? 5. Can you describe the Au-Henkind test for acute iritis, the Wartenberg sign in ulnar nerve palsy, and the Tullio phenomenon as a clue to the cause of vertigo? What are key features of this book? Medical education and clinical experience are remarkably capricious. A newly minted medical graduate may never have seen a patient with Guillain-Barré syndrome or osteomyelitis of the spine. Even the experienced practitioner may never have encountered anyone complaining of pathologically excessive yawning or a patient with suspected cerebrospinal fluid rhinorrhea. Owing to the variability in individual training and experience, each reader will be well acquainted with some of the entities described in this book, considering what I present to be well known and wondering why I included them at all. Others will find this same information to be new knowledge. For the most part, I have attempted to select facts not generally covered in basic physical examination courses or textbooks. Traditional diagnosis books are organized by symptoms and signs—hemoptysis, chest pain or bullous eruption of the skin—in contrast to disease-oriented reference books, which are organized by names of various clinical entities: lung cancer, myocardial infarction, or pemphigus. In this book, I present information under both types of headings, manifestations and diseases. When questions arose, I listed items under the body organ or system in which manifestations are most likely to occur. For example, consider the clue that the patient with herpes zoster who develops a vesicle near the tip of the nose is at risk of developing herpes zoster ophthalmicus; this pearl is presented in Chapter 5 (The Ear, Nose, and Throat) rather than Chapter 4 (The Eye). To save space, and with apologies to all the often-anonymous “et al” co-authors of the world, I have used a shorthand reference style, citing the first author only, plus article title, journal, year, volume and initial page number. Using an abbreviated reference style allows more pages for facts, and still provides enough information to find the article on PubMed, BioMedLib, or Google Scholar. Also, readers will find reference citations listed immediately following the stated fact and commentary, rather than at the end of the chapter; in my own reading I find this placement of references to be especially helpful. In the appendix, I have included a list of a glossary of statistical terms used in the book. This book is literature-based, by which I mean that all facts in this book are found somewhere in the medical literature. Not all assertions, however, are classically evidence-based. We just don’t know with precision (or, at least, I could not locate) the sensitivity or specificity of uncommonly occurring clinical manifestations, such as upbeating nystagmus sometimes observed in Wernicke encephalopathy, or the positive predictive value of some uncommon observations, such ¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬the “red ear syndrome” that has occurred in some patients with migraine. Some phenomena presented, such as yellow vision with digitalis intoxication, represent examples of often-repeated clinical lore, validated by repeated observations of experienced clinicians, and are included because they seem to be have weathered the test of time, supported by a few case reports. But most of what is presented here, such as the positive correlation of a high pulse pressure and white coat hypertension, has been subjected to statistical analysis and peer review. I recognize that some of what I describe is controversial and that future clinical studies may lead us to reconsider what we think is true and wise today. I urge the reader to use this book as a series of prompts, and then consult the current literature before making clinical decisions if in unfamiliar territory. In my research for this book, I found that a number of my reference citations for physical findings and diagnostic maneuvers--such as the Lisker tibial tap sign for deep vein thrombophlebitis of the lower extremity, discussed in Chapter 6--are found in literature that some may call "dated." Today, teaching indicator symptoms and physical biomarkers of disease seems to be out of style in medical school, and as Verghese writes, “Because the echocardiogram, magnetic resonance imaging, and computed tomographic can precisely characterize anatomy, the physical exam is too often viewed as redundant.” [2] I hold that so-called "old-fashioned" historical clues and physical signs are not only part of our medical heritage; their recognition can often spell the difference between prompt identification of disease versus an expensive, time-consuming journey through the clinical laboratory and diagnostic imaging suite. In fact, with the inconsistent quality of medical school teaching regarding the physical examination and the rising costs of high-tech health care, I think this book is needed more than ever. How should you use this book? This is not a classical course text to be studied in a classroom setting. Nor is it a clinical reference book, intended to be “searched,” but not really “read.” This is a “topical” book, presenting a somewhat eclectic collection of facts that someday may prove useful in specific puzzling situations. Hence, the book should be read, cover-to-cover. Put it at your bedside; take it to the beach; enjoy it on a plane trip. The goal is both to learn diagnostic principles and applications today, and to imprint them deep in your memory for future reference. I continue to like my metaphor of “Post-It” notes used to describe my book: Essential Medical Facts Every Clinician Should Know. [3] What you read today may not be clinically pertinent for months or years, but when the time comes, the information is there, “posted” in memory. Then, just to confirm your recollection, you can find it here again using the index provided or perhaps check out the original report on-line. In addition to my “read, post it, recollect, and confirm” approach, the book’s index will be a good place to look when faced with a head-scratching, seemingly unsolvable diagnostic puzzle. Use the index to locate the answers to the five questions posed above. It is axiomatic that the most common diseases occur most commonly. What clinician has not heard the axiom that when you hear hoof-beats, expect to hear horses, not zebras? But it is also true that we all encounter the uncommon entity occasionally, perhaps when we least expect to do so. Knowing the contents of this book can help you recognize the unlikely disease manifestation of a “horse” disorder or spot the “zebra” diagnosis when it presents itself in the middle of a busy office session or on an exam question. Finally, this book is intended to be easy to read, with just enough statistical details to support assertions, without becoming excessively burdened with methodologic minutiae. I have attempted to enrich your knowledge of our heritage by including a few historical anecdotes. And most of all, I have done my best to make this book clinically useful, as the title says: To prevent medical errors Pass board examinations, and Provide informed patient care 1. Jackson C. A new diagnostic sign of foreign body in trachea of bronchi, the “asthmatoid wheeze.” Am J Med Sci. 1918;156:626. 2. Verghese A. Culture shock: patient as icon, icon as patient. N Engl J Med. 2008;359:2748. 3. Taylor R. Essential clinical facts every clinician should know. New York: Springer; 2011. Robert B. Taylor, MD Oregon Health & Science University Portland, Oregon USA taylorr@ohsu.edu
Article
The halo nevus can be defined as a pigmented nevus with an obvious depigmented zone about it. Recent observations have indicated that these lesions will undergo self-involution. This article presents the variety of histopathologic pictures seen and demonstrates the gross clinical changes that can occur in the nevus (change in color, increase in size, scaling, and crusting) during this process of self destruction. The association of these clinical and pathologic changes might make one consider the diagnosis of malignant melanoma. The benign significance of these changes in a halo nevus is stressed. In addition, other aspects of halo nevi such as distribution, configuration, multiplicity, association with vitiligo, and the fate of the halo are presented.
Article
A series of diverse neuroectodermally derived tumors associated with halos of leukoderma is presented. Clinically these lesions have in common a centrally placed, usually pigmented tumor encircled by a zone of hypopigmentation. The histological findings include (1) reduction or absence of epidermal melanin, but persistence of amelanotic melanocytes in the leukodermic halo; (2) a variety of tumors including nevuscell nevus, neuroid nevus, blue nevus, neurofibroma, and malignant melanoma; (3) variable numbers of "small dark cells" whose nature is unclear, and which probably represent in part small nevus cells and in part lymphoid cells; and (4) damage to some tumor cells which presumably could be the cause of their destruction. Also presented are histochemical demonstrations of tyrosinase activity and immunohistochemical studies for presence of γ-globulin in the tumors. Using the fluorescent antibody technique it was not possible to show γ-globulins in patients' sera directed against their tumors. The relationship of developing hypopigmentation to the spontaneous regression of cutaneous neuroectodermally derived tumors is discussed.
Article
The Journal of Investigative Dermatology publishes basic and clinical research in cutaneous biology and skin disease.
Article
—A study has been made on the incidence of vitiligo in mature-onset diabetics attending hospital. An increased incidence of vitiligo was found in the whole group of diabetics, and in the female diabetics, when compared with controls. In more than half the patients with both vitiligo and diabetes, the vitiligo preceded the diabetes. Vitiligo begins before the age of 40 in over 80% of all cases but did so in only 24% of 25 diabetics with vitiligo.
Article
There is a significant association between vitiligo and thyroid disease. Thyroglobulin antibodies are significantly associated with vitiligo, whether patients with psoriasis or a general practice population are taken as controls. Similarly complement-fixing antibodies are significantly associated with vitiligo as compared with psoriasis. There is no evidence that thyroid autoimmunity is associated positively or negatively with psoriasis. Alopecia areata, pernicious anaemia and diabetes mellitus are also significantly associated with vitiligo.
Article
The subject was a 14-year-old boy with Sutton's disease (leukoderma acquisitum centrifugum). Nine halo nevi were removed from his skin: seven from the trunk, one from the neck, and one from the deltoid area. Seven were examined with the light microscope, and all presented similar histologic findings. Two of the lesions were examined with the electron microscope, one in our laboratory and one at Harvard Medical School. In the depigmented epidermis of the halo we found active melanocytes. No melanocytes were found in the halo epidermis at Harvard. Lymphocytes and nevus cells were present in the nevus area of both specimens. There was evidence of cytotoxic effect in nevus cells and some melanocytes. A hypothetical sequence of immunologic events to account for the halo development is presented.
Article
— The association of vitiligo with organ-specific autoimmune disorders has been examined with particular reference to pernicious anaemia. A significantly increased incidence of gastric parietal cell antibody was found in serum of sixty-two patients with vitiligo. There is now sufficient clinical and investigative evidence to suggest that absence of melanocytes from lesions of vitiligo results from immunological disturbance.
Article
A series of diverse neuroectodermally derived tumors associated with halos of leukoderma is presented. Clinically these lesions have in common a centrally placed, usually pigmented tumor encircled by a zone of hypopigmentation. The histological findings include (1) reduction or absence of epidermal melanin, but persistence of amelanotic melanocytes in the leukodermic halo; (2) a variety of tumors including nevus-cell nevus, neuroid nevus, blue nevus, neurofibroma, and malignant melanoma; (3) variable numbers of "small dark cells" whose nature is unclear, and which probably represent in part small nevus cells and in part lymphoid cells; and (4) damage to some tumor cells which presumably could be the cause of their destruction. Also presented are histochemical demonstrations of tyrosinase activity and immunohistochemical studies for presence of gamma-globulin in the tumors. Using the fluorescent antibody technique it was not possible to show gamma-globulins in patients' sera directed against their tumors. The relationship of developing hypopigmentation to the spontaneous regression of cutaneous neuroectodermally derived tumors is discussed.
Eighty-six Cases of Addison's Disease Halo Nevus. Archs Derm Broad Spectrum of Leukoderma Acquisitum Centrifugum
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DAWBER, R. P. R. (1968) Vitiligo in Mature-onset Diabetes Mellitus. Br. J. Derm., 80, 275. DuNLOi", D. (1963) Eighty-six Cases of Addison's Disease. Br. med. J., ii, 887. FRANK, S. B. and COHEN, H. J. (1964) Halo Nevus. Archs Derm., 89, 367. KOPF, A. W., MORBILL, S. D. and SILBERBEBG, I. (1965) Broad Spectrum of Leukoderma Acquisitum Centrifugum. Archs Derm., 92. 14. KOPF, A. W. (1969) In Discussion. Archs Derm., 99, 187. LANOHOF, H., FEUERSTEIN, M. and SCHABINSKI, G. (1965) Melaninantikorperbildung bei Vitilieo Hautarzt, 16, 209. LEBNER, A. B. (1959) Vitiligo. J. invest. Derm., 32, 285. PITT-RIVERS, R. and TROTTER, W. R. (1964) The Thyroid Gland. Vol.
Birkett for constructive criticism, and Miss Eva Bottoms for invaluable statistical help Vitiligo and Its Aetiologioal Relationship to Organ-specific Auto-immune Disease
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I wish to thank the many physicians who allowed me to see their patients, Dr C. J. Stevenson and Professor S. Shuster for considerable help, Dr M. Greaves and Dr D. A. Birkett for constructive criticism, and Miss Eva Bottoms for invaluable statistical help. REFERENCES BOB, S., FEIWEL, M. and CHANABIN, I. (1969) Vitiligo and Its Aetiologioal Relationship to Organ-specific Auto-immune Disease. Br. J. Derm., 81, 83. CUNLIFFE, W. J., HAIL, R., NEWELL, D. J. and STEVENSON, C. J. (1968) Vitiligo, Thyroid Disease and Auto-immunity. Br. J. Derm., 80, 135.