Satoyoshi syndrome: a cause of alopecia universalis in association with neurologic and bony abnormalities.

Satoyoshi syndrome is a rare multisystemic disorder characterized by alopecia, diarrhea, muscle spasms, osseous abnormalities, and endocrinopathies. We report a case of Satoyoshi syndrome misdiagnosed as vitamin D-dependent rickets for several years.

Photoletter to the editor: Dyschromatosis universalis hereditaria: an infrequently occurring entity in Europe.

Dyschromatosis universalis hereditaria (DUH) is a rare genodermatosis mainly described in asian subjects. Here, we report a case of a caucasian 11-year-old boy with DUH and an unaffected twin brother. Parents were not consanguineous. A review of the main phenotical, clinical and hystological aspects of this rare entity is exhibited. Differential diagnose might be stablished with several pigmentary disorders, so Dermatologist might have this entity in mind to make a correct diagnose, specially in cases with no response to typical treatments.

When are laboratory tests indicated in patients with vitiligo?

BACKGROUND: Vitiligo has been associated with multiple endocrine and immune conditions. Several laboratory tests have been assessed in this disease with controversial results. OBJECTIVE: The aim of this study is to analyze the levels autoantibodies, basal glycaemia, vitamin B12, folic acid and thyroid function and its association with the diagnosis and outcome of vitiligo patients through a case-control study. MATERIAL AND METHODS: This case-control study was performed on 196 consecutive patients with vitiligo referred to our Dermatology Department. As a control group, 160 healthy individuals without vitiligo or known history of immunologic/endocrine disease were included. Data were analyzed using the SPSS 17.0 statistical software package. RESULTS: Clinical, analytical and demographic data have been recorded. Our results showed that anti-thyroid peroxidase antibody and anti-parietal gastric cell antibody could be useful laboratory markers in a subpopulation of vitiligo patients. However, testing anti-nuclear antibody, anti-thyroglobulin antibody, folic acid and vitamin B12 seems to have limited clinical implication and diagnostic relevance in our routine clinical practice. LIMITATIONS: This study addressed a selected population of vitiligo patients in Spain and may not generalize to different clinical settings or regions. The study of a wider sample would confirm these findings and allow a detailed analysis of the above factors as a function of the clinical subtype of vitiligo. CONCLUSION: We have determined the more efficient serological markers to order in vitiligo patients. Our findings suggest that anti-thyroid peroxidase antibody and anti-parietal gastric cell could be useful tests for the characterization of specific subpopulations of vitiligo patients in terms of severity and co-morbidity, so their determination could have a prognostic value.

Urea uptake enhances barrier function and antimicrobial defense in humans by regulating epidermal gene expression.

Urea is an endogenous metabolite, known to enhance stratum corneum hydration. Yet, topical urea anecdotally also improves permeability barrier function, and it appears to exhibit antimicrobial activity. Hence, we hypothesized that urea is not merely a passive metabolite, but a small-molecule regulator of epidermal structure and function. In 21 human volunteers, topical urea improved barrier function in parallel with enhanced antimicrobial peptide (AMP; LL-37 and ß-defensin-2) expression. Urea stimulates the expression of, and is transported into, keratinocytes by two urea transporters (UTs), UT-A1 and UT-A2, and by aquaporins 3, 7, and 9. Inhibitors of these UTs block the downstream biological effects of urea, which include increased mRNA and protein levels of (i) transglutaminase-1, involucrin, loricrin, and filaggrin, (ii) epidermal lipid synthetic enzymes, and (iii) cathelicidin/LL-37 and ß-defensin-2. Finally, we explored the potential clinical utility of urea, showing that topical urea applications normalized both barrier function and AMP expression in a murine model of atopic dermatitis. Together, these results show that urea is a small-molecule regulator of epidermal permeability barrier function and AMP expression after transporter uptake, followed by gene regulatory activity in normal epidermis, with potential therapeutic applications in diseased skin.

Expression of epidermal CAMP changes in parallel with permeability barrier status.

Two critical defensive functions of the outer epidermis, the permeability barrier and antimicrobial defense, share certain structural and biochemical features. Moreover, three antimicrobial peptides (AMPs), i.e., mouse ß-defensin 3 (mBD3), mouse cathelicidin antimicrobial peptide (mCAMP), and the neuroendocrine peptide, catestatin (Cst), all localize to the outer epidermis, and both mBD3 and mCAMP are secreted from the epidermal lamellar bodies with other organelle contents that subserve the permeability barrier. These three AMPs are upregulated in response to acute permeability barrier disruption, whereas conversely, mCAMP-/- mice (unable to combat Gram-positive pathogens) also display abnormal barrier homeostasis. To determine further whether these two functions are co-regulated, we investigated changes in immunostaining for these three AMPs in skin samples in which the permeability barrier function in mice had been either compromised or enhanced. Compromised or enhanced barrier function correlated with reduced or enhanced immunohistochemical expression of mCAMP, respectively, but conversely with Cst expression, likely due to the role of this AMP as an endogenous inhibitor of cathelicidin expression. mBD3 expression correlated with experimental barrier perturbations, but poorly with developmental changes in barrier function. These studies show that changes in cathelicidin and Cst expression parallel changes in permeability barrier status, with a less clear relationship with mBD3 expression.

Pathogenesis-based therapy reverses cutaneous abnormalities in an inherited disorder of distal cholesterol metabolism.

Identification of the underlying genetic, cellular, and biochemical basis of lipid metabolic disorders provides an opportunity to deploy corrective, mechanism-targeted, topical therapy. We assessed this therapeutic approach in two patients with Congenital Hemidysplasia with Ichthyosiform erythroderma and Limb Defects (CHILD) syndrome, an X-linked dominant disorder of distal cholesterol metabolism. On the basis of the putative pathogenic role of both pathway-product deficiency of cholesterol and accumulation of toxic metabolic intermediates, we assessed the efficacy of combined therapy with lovastatin and cholesterol. We also evaluated the basis for the poorly understood, unique lateralization of the cutaneous and bone malformations of CHILD syndrome by analyzing gene activation in abnormal and unaffected skin. Ultrastructural analysis of affected skin showed evidence of both cholesterol depletion and toxic metabolic accumulation. Topical treatment with lovastatin/cholesterol (but not cholesterol alone) virtually cleared skin lesions by 3 months, accompanied by histological and ultrastructural normalization of epidermal structure and lipid secretion. The unusual lateralization of abnormalities in CHILD syndrome reflects selective clearance of keratinocytes and fibroblasts that express the mutant allele from the unaffected side. These findings validate pathogenesis-based therapy that provides the deficient end product and prevents accumulation of toxic metabolites, an approach of potential utility for other syndromic lipid metabolic disorders.

Pathogenesis of the cutaneous phenotype in inherited disorders of cholesterol metabolism: Therapeutic implications for topical treatment of these disorders.

Molecular geneticists tend to conceptualize disease pathogenesis from the mutated gene outward, an approach that does not take into account the impact of barrier requirements in determining disease phenotype. An 'outside-to-inside' perspective has provided quite different explanations for the ichthyoses, including several of the disorders of distal cholesterol metabolism. Elucidation of responsible pathogenic mechanisms also is pointing to appropriate, pathogenesis (pathway)-based therapeutic strategies. In the case of the lipid metabolic disorders, it takes full advantage of new molecular, genetic and cellular pathogenesis information to correct or bypass the metabolic abnormality. This approach fully exploits the unique accessibility of the skin to a topical approach. Moreover, since it will utilize topical lipids and lipid-soluble, and often generic, lipid-soluble drugs, these treatments should be readily transported across the stratum corneum. If successful, this approach could initiate an entirely new departure for the therapy of the ichthyoses. Finally, because these agents are relatively safe and inexpensive, this form of treatment has the potential to be widely-deployed, even in the developing world.

Psychological stress regulates antimicrobial peptide expression by both glucocorticoid and ß-adrenergic mechanisms.

Psychological stress (PS) exerts well-known negative consequences for permeability barrier function in humans and mice, and deterioration of barrier function appears to be attributable largely to excess production of endogenous glucocorticoids (GC). More recently, PS has been shown to compromise antimicrobial defense, also by GC-dependent mechanisms. We assessed here changes in a third antimicrobial peptide (AMP); i.e., the neuropeptide, catestatin (Cst), which also is expressed in the outer epidermis, and previously shown to be regulated by changes in permeability barrier status. In these studies, PS again provoked a decline in both mouse cathelicidin (CAMP) and mouse ß-defensin 3 (mBD3) expression, in a GC-dependent fashion. In contrast, Cst immunostaining instead increased after short-term PS, but then began to decline with more sustained PS. In cultured keratinocytes, we showed further that GC downregulate Cst expression, but ß-adrenergic blockade increased immunostaining for Cst in the face of long-term PS. Furthermore, ß-adrenergic blockade also upregulated CAMP and mBD3 expression. Together, these results suggest that both endogenous GC and ß-adrenergic signaling regulate AMP expression.

Cutaneous lesions as presentation form of mantle cell lymphoma.

Mantle cell lymphoma is a type of non-Hodgkin lymphoma that affects extranodal areas, especially, bone narrow, digestive tract and Waldeyer ring. Here we report a case of mantle cell lymphoma IV Ann Arbor stage with cutaneous lesions on nasal dorsum and glans penis as the first manifestations. Skin involvement is a very rare manifestation and less than 20 cases have been reported in the literature. The importance of establishing multidisciplinary relationships for a global approach has been shown by this clinical case.

An unusual case of congenital linear eccrine spiradenoma.

Eccrine spiradenoma (ES) is a benign uncommon tumor of skin adnexa with a characteristic clinical and histopathological presentation. Typically, it presents as a painful, slow growing and solitary nodule on the head or upper trunk in adult patients. We report a child with linear ES which presented with asymptomatic papulonodular lesions in a blaschkoid distribution on the face. Cases reported in the literature of multiple spiradenomas are very rare and multiple linear lesions are even rarer. To date, 21 cases of linear/multiple ES have been reported. Of these, eight were in children or adolescents. We report an additional case of this rare clinical presentation and review the literature.

Pápulas pruriginosas en axilas / Pruritic papules in the axillae

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