Comparative analysis of the expression of cytokeratins (1,10,14,16,4), involucrin, filaggrin and e-cadherin in plane warts and epidermodysplasia verruciformis plane wart-type lesions

Background: Epidermodysplasia verruciformis (EV) is a rare genodermatosis with susceptibility to human papillomavirus (HPV) infection, and high risk of skin cancer considered a model of viral oncogenesis. Methods: Fifteen cases of EV plane wart (PW)-type lesions (EV) and 14 cases of PW in healthy individuals were subjected to immunohistochemical technique for cytokeratins (K) 1, 10, 14, 16, 4, involucrin, filaggrin and e-cadherin. Results: K1/10 showed retarded or negative expression in EV, being substituted by K14. Expression of K14 occurred in the basal and suprabasal layers in both groups, but in EV, its expression was observed up to the more superficial layers. Both groups showed positivity for K16 and K4, involucrin expression in lower levels of the spinous layer and unaltered filaggrin expression. E-cadherin expression was diminished at the koilocytotic foci of both lesions, more superficially in EV. Conclusion: Infection by HPV may alter the differentiation status of the epidermis, leading to a major expression of K14, delayed or absent expression of K1/10 and earlier involucrin expression, especially in EV. It also stimulates the expression of K16 and K4. Filaggrin expression is not altered, and e-cadherin is diminished in superficial koilocytotic cells` foci in EV.

Primary Cutaneous Blastoid Mantle Cell Lymphoma-Case Report

Mantle cell lymphoma (MCL) commonly involves extranodal sites, usually as a manifestation of disseminated disease. In rare cases, MCLs may arise as a primary tumor in the skin. Blastoid mantle cell lymphoma (BV-MCL) is a rare variant and has a more aggressive clinical course. The phenotype of BV-MCL is characterized as CD20(+), CD5(+), cyclin D1(+), CD23(-), and CD10(-). Interphase fluorescence in situ hybridization shows a characteristic t(11; 14) fusion pattern. We report a case of a BV-MCL arising in skin as primary cutaneous MCL with the characteristic immunophenotype and translocation.

Clinicopathological evaluation of in vivo epidermal nuclear fluorescence

Nuclear fluorescence in keratinocytes is an occasional phenomenon, often present in autoimmune diseases, especially in connective-tissue disease (CTD); however, its clinical significance remains unclear. To investigate the profile of patients with positive nuclear staining on direct immunofluorescence (DIF) of skin samples. A retrospective analysis of 28 patient records from our immunodermatology laboratory was performed between May 2003 and June 2006. Inclusion criteria were the presence of autoantibodies (IgG, IgA or IgM) or complement (C3) binding keratinocyte nuclei on DIF. The most prevalent diseases related to the nuclear keratinocyte DIF staining were systemic lupus erythematosus (n = 9), mixed CTD (n = 3), overlap syndrome (n = 3), Sjogren`s syndrome (n = 1), and CREST (calcinosis, Raynaud`s phenomenon, oesophageal dysmotility, sclerodactyly and telangiectasia) syndrome (n = 1). Serum antinuclear antibody (ANA) was positive in 20 of 28 patients, with titres varying from 1 : 160 to 1 : 1280. Of the 20 patients with positive anti-nuclear antibodies (ANA), 17 were positive for anti-extractable nuclear antigen antibodies, 12 had anti-SSA/Ro, 11 had anti-SSB/La and 8 had anti-ribonucleoprotein. Eight patients were negative for ANA. Positive predictive value of in vivo ANA for systemic CTDs was 75%. The present data suggest that in vivo ANA evaluation is an additional and feasible auxiliary tool for diagnosing CTDs.

Inflammatory epidermolysis bullosa acquisita - Case report

We report a case of an inflammatory variant of epidermolysis bullosa acquisita in a 53-year-old male, with itching blistering eruption on the trunk, armpits and limbs for six months. The skin biopsy specimen showed subepidermal blister with neutrophils. Direct immunofluorescence revealed linear depositions of IgG, IgA, IgM and C3 at the basement membrane; indirect immunofluorescence and salt split skin were negative. Antinuclear antibodies were also negative. Improvement of the blisters followed treatment with systemic corticotherapy and some lesions healed with milia. This is a rare presentation of epidermolysis bullosa acquisita, with inflammatory lesions at first.

Erythema elevatum diutinum presenting with a giant annular pattern

A 45-year-old woman presented with a 3-year history of cutaneous lesions. Clinical examination revealed red-yellow to brownish infiltrated papules coalescing into annular-shaped plaques of several sizes with a hyperpigmented center affecting the abdomen and lower limbs, as well as multiple firm nodules on the right palm, elbows, and knees (Fig. 1a-c). The patient also reported sporadic arthralgia and low fever. She had been treated for leprosy for 2 years with multidrug therapy (clofazimine, dapsone, and rifampicin), with complete remission of the lesions during treatment, but recurrence after discontinuation. Histologic examination of a biopsy specimen taken from the cutaneous lesions showed an interstitial inflammatory infiltrate with the presence of many neutrophils and occasional foamy histiocytes (Fig. 2a). A pattern of perivascular eosinophilic fibrosis was observed in a biopsy specimen from a nodule (Fig. 2b). Special stains for acid-fast bacilli and fungi were negative. Laboratory findings included elevated immunoglobulin A (IgA) serum levels (1016 mg/dL; normal range, 69-382 mg/dL), elevated beta-globulin, and strong tuberculin reactivity. Normal or negative tests included direct immunofluorescence, serum immunofixation, anti-streptolysin O, and chest radiography. Autoimmune disorders and inflammatory intestinal diseases were excluded. The patient was treated with dapsone, 100 mg/day, with great improvement of the clinical picture. Hyperpigmented residual macules and some fibrotic nodules remained after 3 months.

Inducible nitric oxide synthase in pityriasis lichenoides lesions

Pityriasis lichenoides (PL) is an inflammatory skin disease of unknown etiology. Nitric oxide (NO) has emerged as an important mediator of many physiological functions. The importance of NO-mediated signaling in skin diseases has been reported by several studies. A review of clinical records and histopathological slides of 34 patients diagnosed with PL was performed. Three different groups of skin biopsies including PL chronica (24 patients), PL et varioliformis acuta (10 patients) and 15 normal skin samples were subjected to the immunohistochemistry technique for inducible nitric oxide synthase (iNOS) detection. Normal skin group exhibited a few number of iNOS-positive cells in the dermis and rare positive cells in the upper epidermis, unlike abundant epidermal and dermal iNOS expression observed in both PL groups. According to our results, we hypothesize that NO produced by iNOS could participate in PL pathogenesis. Abnormal and persistent responses to unknown antigens, probably a pathogen, associated with NO immunoregulatory functions could contribute to the relapsing course observed in PL. NO anti-apoptotic effect on T-cell lymphocytes could play a role on maintenance of reactive T cells, leading to a T-cell lymphoid dyscrasia. Di Giunta G, Goncalves da Silva AM, Sotto MN. Inducible nitric oxide synthase in pityriasis lichenoides lesions.J Cutan Pathol 2009; 36: 325-330. (C) Blackwell Munksgaard 2008.

Fibroblastic rheumatism

Fibroblastic rheumatism (FR) was first described in 1980 by Chaouat et al., and there have been few cases reported to date. The cause remains unknown. We report the first Latin-American patient with FR, to our knowledge, who is also the patient with the most striking dermatological features described in the literature. The diagnosis was based on the presence of a number of typical features. Clinically, the patient presented skin nodules and polyarthropathy with flexion contractures of the fingers. The histological findings compressed fibroblastic proliferation, thickened collagen fibres, dermal fibrosis and a decreased number of elastic fibres. Immunoreactivity for beta-catenin, alpha-smooth muscle actin and the monoclonal antibody HHF-35 showed myofibroblastic differentiation. Treatment with prednisone slightly reduced the number of nodules but did not improve the rheumatological symptoms. This condition has shown a poor response to many treatments proposed by previous authors. Further study will be necessary to identify effective treatment.

Pathogenesis of Endemic Pemphigus Foliaceus

Pemphigus refers to a group of human autoimmune blistering diseases involving skin and/or mucous membranes. Endemic pemphigus foliaceus (EPF), or fogo selvagem is an organ-specific autoimmune blistering disease, first reported in the beginning of the 20th century in rural areas of Brazil. The disease follows the course of streams and creeks, and vanishes after urbanization of the endemic areas. The auto-antigen related to EPF is desmoglein 1, a 160 kDa glycoprotein of the desmossomal core, targeted by in situ and circulating IgG autoantibodies, mainly of the IgG4 subclass.

Development of an IgG4-Based Predictor of Endemic Pemphigus Foliaceus (Fogo Selvagem)

Fogo selvagem (FS) is mediated by pathogenic, predominantly IgG4, anti-desmoglein 1 (Dsg1) autoantibodies and is endemic in Limao Verde, Brazil. IgG and IgG subclass autoantibodies were tested in a sample of 214 FS patients and 261 healthy controls by Dsg1 ELISA. For model selection, the sample was randomly divided into training (50%), validation (25%), and test (25%) sets. Using the training and validation sets, IgG4 was chosen as the best predictor of FS, with index values above 6.43 classified as FS. Using the test set, IgG4 has sensitivity of 92% (95% confidence interval (95% CI): 82-95%), specificity of 97% (95% CI: 89-100%), and area under the curve of 0.97 ( 95% CI: 0.94-1.00). The IgG4 positive predictive value (PPV) in Limao Verde (3% FS prevalence) was 49%. The sensitivity, specificity, and PPV of IgG anti-Dsg1 were 87, 91, and 23%, respectively. The IgG4-based classifier was validated by testing 11 FS patients before and after clinical disease and 60 Japanese pemphigus foliaceus patients. It classified 21 of 96 normal individuals from a Limao Verde cohort as having FS serology. On the basis of its PPV, half of the 21 individuals may currently have preclinical FS and could develop clinical disease in the future. Identifying individuals during preclinical FS will enhance our ability to identify the etiological agent(s) triggering FS.

Remission of extensive lentigo maligna after treatment with imiquimod

Lentigno maligna is a melanoma in situ that most commonly appears on areas exposed to ultraviolet radiation, in elderly patients. Treatment is required mainly to minimize the risk of progression to lentigo maligna melanoma. The present report refers to an elderly patient with recurrent lesions of lentigo maligna in her face, who was successfully treated with topical imiquimod, which showed to be a useful therapy for some cases of the disease.

Cutaneous manifestations of thrombophilia

The aim of this article is to review the hypercoagulable states (thrombophilia) most probably found by dermatologists; their cutaneous signs including livedo racemosa, skin necrosis, digital ischemia and ulcerations, retiform purpura and leg ulcers; their appropriate treatment; to describe the skin manifestations that require laboratory tests for thrombophilias and the tests indicated in these clinical conditions.

A 65-year experience treating acne, including 26 years with oral isotretinoin

This special article is based on the contents of a lecture given by Sampaio and was written together with Bagatin. it is a summary of the authors` experience treating various forms of acne before and after the introduction of oral isotretinoin, which revolutionized the management of the disease. Nowadays, this drug is considered the unique option to obtain a prolonged remission or cure of acne due to its action in all etiopathogenic factors involved in the disease. Therefore it should be prescribed in accordance to current recommendations, as well as for difficult cases, including those showing tendency to scars or serious psychological and social repercussions. Other topical and/or systemic therapeutic modalities should be considered in the initial approach and for mild and moderate cases.

Lymphocyte proliferation testing in chromium allergic contact dermatitis

Background. Lymphocyte proliferation testing (LPT) has some advantages over patch testing to diagnose allergic contact dermatitis. It is harmless, objective and can be used in clinical situations where patch testing is not recommended. Unfortunately, significant success has only been achieved with nickel. There are few studies on chromium LPT and they were performed with different methods, leading to inconsistent results. Methods. To determine the best parameters for chromium LPT, we tested 20 patients with allergic contact dermatitis to the metal and 20 controls, using various protocols. Results. The best sensitivity and specificity ratios were achieved with 6-day cultures stimulated with a range from 7.5 x 10(-4) to 5 x 10(-3) mol/L of nonfiltered chromium chloride solutions. The sensitivity, specificity and accuracy values found within this range were 65%, 95% and 80%, respectively. Conclusion. Further investigation is necessary to achieve better sensitivity values.

Predictors of higher number of stages in Mohs micrographic surgery for the treatment of squamous cell carcinoma of the head

BACKGROUND - Squamous cell carcinomas of the skin of the bead are better treated with Mobs micrographic surgery which has the lowest recurrence rates and allows spare normal tissue. There are some characteristics of squamous cell carcinoma that can be related to a higher number of surgical stages. OBJECTIVE - To study characteristic of head squamous cell carcinoma that predicts a higher number of Mohs surgical stages. METHODS - A retrospective analysis of 51 squamous cell carcinomas of the bead treated with Mobs surgery was performed to determine risk factors for a higher number of surgical stages. The characteristics analyzed were clinical limits, morphology, recurrence, histological differentiation and size and compared to the number of surgical stages. The analysis was performed by Fisher`s exact test and multivariate logistic regression. RESULTS - The recurrent squamous cell carcinomas showed a tendency for a higher number of stages (p=0,081). The Odds Ratio for a higher number of Mobs stages was three for inaccurate limits; although not statistically significant, it corroborates clinical and previous publication. CONCLUSION - Clinical characteristics of squamous cell carcinoma as recurrence and inaccurate limits would not predict, but could indicate tendency of a higher number of Mobs micrographic surgery stages.

The IgM anti-desmoglein 1 response distinguishes Brazilian pemphigus foliaceus (Fogo selvagem) from other forms of pemphigus

Fogo selvagern (FS) and pemphigus foliaceus (PF) possess pathogenic IgG anti-desmoglein 1-(Dsg1) autoantibodies. Although PF occurs sporadically, FS is endemic in Limao Verde (LV), Brazil (3.4% prevalence). IgM anti-Dsg1 were detected in 58% FS LV patients (n=31), 19% of FS patients from Hospital-Campo Grande (n=57), 19% from Hospital-Goiania (n=42), 12% from Hospital-Sao Paulo (n=56), 10% of PF patients from United States (n=20), and 0% of PF patients from Japan (n=20). Pemphigus vulgaris (n=40, USA and Japan), bullous pemphigoid (n=40, USA), and healthy donors (n=55, USA) showed negligible percentages of positive sera. High percentages of positive IgM anti-Dsg1 were found in healthy donors from four rural Amerindian populations (42% of 243) as compared with urban donors (14% of 81; P<0.001). More than 50% of healthy donors from LV (n=99, age 5-20 years) possess IgM anti-Dsg1 across ages, whereas IgG-anti-Dsg1 was detected in 2.9% (age 5-10 years), 7.3% (age 11-15 years), and 29% of donors above age 16. IgM anti-Dsg1 epitopes are Ca2+ and carbohydrate-independent. We propose that IgM anti-Dsg1 are common in FS patients in their native environment and uncommon in other pemphigus phenotypes and in FS patients who migrate to urban hospitals. Recurrent environmental antigenic exposure may lead to IgM and IgG responses that trigger TS.