IgG4-related skin disease.

IgG4-related disease (IgG4-RD) is a recently established clinical entity characterized by high levels of circulating IgG4, and tissue infiltration of IgG4(+) plasma cells. IgG4-RD exhibits a distinctive fibroinflammatory change involving multiple organs, such as the pancreas and salivary and lacrimal glands. The skin lesions of IgG4-RD have been poorly characterized and may stem not only from direct infiltration of plasma cells but also from IgG4-mediated inflammation. Based on the documented cases together with ours, we categorized the skin lesions into seven subtypes: (1) cutaneous plasmacytosis (multiple papulonodules or indurations on the trunk and proximal part of the limbs), (2) pseudolymphoma and angiolymphoid hyperplasia with eosinophilia (plaques and papulonodules mainly on the periauricular, cheek and mandible regions), (3) Mikulicz disease (palpebral swelling, sicca syndrome and exophthalmos), (4) psoriasis-like eruption (strikingly mimicking psoriasis vulgaris), (5) unspecified maculopapular or erythematous eruptions, (6) hypergammaglobulinaemic purpura (bilateral asymmetrical palpable purpuric lesions on the lower extremities) and urticarial vasculitis (prolonged urticarial lesions occasionally with purpura) and (7) ischaemic digit (Raynaud phenomenon and digital gangrene). It is considered that subtypes 1-3 are induced by direct infiltration of IgG4(+) plasma cells, while the other types (4-7) are caused by secondary mechanisms. IgG4-related skin disease is defined as IgG4(+) plasma-cell-infiltrating skin lesions that form plaques, nodules or tumours (types 1-3), but may manifest secondary lesions caused by IgG4(+) plasma cells and/or IgG4 (types 4-7).

Skin-homing Th2/Th22 cells in papuloerythroderma of Ofuji.

Papuloerythroderma of Ofuji (PEO) appears to be a T cell-mediated skin disease; however, the pathogenesis of PEO remains unclear. We report two cases of PEO and examine cytokine production and expression of skin-homing receptors in circulating T cells in the patients. The percentages of interleukin 4 (IL-4)-, IL-13- and IL-22-producing CD4+ and CD8+ T cells were markedly higher in the circulation of patients with PEO than in those of healthy subjects. The expression of both cutaneous lymphocyte antigen (CLA) and CC chemokine receptor 4 (CCR4) were significantly upregulated in the circulating CD4+ and CD8+ T cells. Moreover, serum levels of thymus and activation-regulated chemokine (TARC), a chemoattractant for CCR4, were increased. The number of IL-4-, IL-13- and IL-22-producing T cells, expression of CLA and CCR4 by T cells, and serum TARC levels significantly decreased after complete remission of PEO. These results suggest that skin-homing Th2/Th22 cells may play a role in the pathogenesis of PEO.

Pruritic papular eruption and eosinophilic folliculitis associated with human immunodeficiency virus (HIV) infection: a histopathological and immunohistochemical comparative study.

BACKGROUND: Among the papular-pruriginous dermatoses related to human immunodeficiency (HIV) infection, two entities remain poorly differentiated leading to confusion in their diagnosis: HIV-related pruritic papular eruption (HIV-PPE or prurigo) and eosinophilic folliculitis (HIV-EF). OBJECTIVE: To establish histopathological and immunohistochemical parameters to differentiate between two conditions associated with HIV infection, the pruritic papular eruption (HIV-PPE) and eosinophilic folliculitis (HIV-EF). METHODS: Clinically typical HIV-PPE (18 cases) and HIV-EF (10 cases) cases were compared with each other in terms of the following topics: clinical and laboratory features (gender, age, CD4+ cell and eosinophil count), histopathological features (hematoxylin-eosin and toluidine blue staining) and immunohistochemical features (anti-CD1a, anti-CD4, anti-CD7, anti-CD8, anti-CD15, anti-CD20, anti-CD30, anti-CD68/macrophage and anti-S-100 reactions). RESULTS: Among the HIV-EF patients, we found an intense perivascular and diffuse inflammatory infiltration compared with those patients with HIV-PPE. The tissue mast cell count by toluidine staining was higher in the HIV-EF patients, who also presented higher expression levels of CD15 (for eosinophils), CD4 (T helper), and CD7 (pan-T lymphocytes) than the HIV-PPE patients. LIMITATIONS: Only quantitative differences and not qualitative differences were found. CONCLUSIONS: These data indicate that HIV-related PPE and EF could possibly be differentiated by histopathological and immunohistochemical findings in addition to clinical characteristics. In fact, these two inflammatory manifestations could be within the spectrum of the same disease because only quantitative, and not qualitative, differences were found.

Autoinflammatory keratinization diseases: An emerging concept encompassing various inflammatory keratinization disorders of the skin.

Classifying inflammatory skin diseases is challenging, especially for the expanding group of disorders triggered by genetic factors resulting in hyperactivated innate immunity that result in overlapping patterns of dermal and epidermal inflammation with hyperkeratosis. For such conditions, the umbrella term "autoinflammatory keratinization diseases" (AIKD) has been proposed. AIKD encompasses diseases with mixed pathomechanisms of autoinflammation and autoimmunity, and includes IL-36 receptor antagonist (IL-36Ra)-related pustulosis, CARD14-mediated pustular psoriasis, pityriasis rubra pilaris (PRP) type V, and familial keratosis lichenoides chronica (KLC). Mechanistically, the entities include generalized pustular psoriasis (GPP) without psoriasis vulgaris, impetigo herpetiformis and acrodermatitis continua, which are IL-36Ra-related pustuloses caused by loss-of-function mutations in IL36RN; GPP with psoriasis vulgaris and palmoplantar pustular psoriasis which are CARD14-mediated pustular psoriasiform dermatoses with gain-of-function variants of CARD14; PRP type V which is caused by gain-of-function mutations in CARD14; and, familial KLC in which mutations in NLRP1, an inflammasome sensor protein predominantly expressed in skin, have been identified. It is likely that further inflammatory keratinization disorders will also fall within the concept of AIKD, as elucidation of novel pathogenic mechanisms of inflammatory keratinization diseases emerges. A better understanding of the pathophysiology of AIKD is likely to lead to innovative, targeted therapies that benefit patients.

Cyclosporin-induced sebaceous hyperplasia in renal transplant patients.

INTRODUCTION: Sebaceous hyperplasia is associated with immunosuppressive treatment with cyclosporin in male renal transplant patients. This has not been reported in the local context. CLINICAL PICTURE: This is a report on 2 Chinese renal transplant patients on cyclosporin who developed sebaceous hyperplasia. TREATMENT AND OUTCOME: One patient was treated with carbon dioxide laser. The result was good and the patient was satisfied with the procedure. CONCLUSION: Cyclosporin-induced sebaceous hyperplasia is likely to be a direct and casual effect of cyclosporin, and to be unrelated to immunosuppressive action. However, further studies are needed to find out whether sebaceous hyperplasia is a dysplastic process or tumour progression in genetically susceptible patients under the effect of immunosuppression.

Clinical and histopathologic features and immunologic variables in patients with severe chilblains. A study of the relationship to lupus erythematosus.

We investigated 33 patients affected with chilblain lesions following a persisting course of more than 1 month. We focused on the incidence of an underlying connective tissue disease, mostly lupus erythematosus (LE), and we analyzed features of idiopathic chilblains compared with those of chilblain lesions associated with connective tissue disease. We also carried out a prospective follow-up of patients. Eleven patients included in the study were free of any clinical and/or laboratory abnormality suggestive of connective tissue disease, while 22 of 33 patients showed 1 or several abnormalities raising suspicion for connective tissue disease, and among them 8 had a diagnosis of systemic lupus erythematosus (SLE) established at initial evaluation based on the American College of Rheumatology revised criteria. The comparative analysis of patients with idiopathic chilblains and patients with chilblains associated with LE showed that female sex and persistence of lesions beyond cold seasons were significantly associated with chilblain LE. Histopathologic studies of chilblain lesions did not reveal features typical of LE in any case, but revealed a higher incidence of a deep perisudoral infiltrate in idiopathic chilblains. In patients showing signs of connective tissue disease, positive cutaneous immunofluorescence was correlated with the presence of circulating antinuclear antibodies. Two patients had an ascertained diagnosis of SLE with severe manifestations during prospective follow-up, requiring treatment with oral steroids in both cases. Chilblains following a chronic course may reveal connective tissue disease, and patients affected with chilblains associated with autoimmune abnormalities may develop severe SLE. Accordingly, long-term follow-up of these patients is warranted.

Response to smallpox vaccine in persons immunized in the distant past.

CONTEXT: There is renewed interest in use of smallpox vaccine due to the potential for a bioterrorist attack. This would involve vaccinating health care workers who were previously vaccinated. OBJECTIVE: To evaluate the use of diluted vaccinia virus in vaccination of previously vaccinated (non-naive) participants. DESIGN, SETTING, AND PARTICIPANTS: Eighty non-naive participants, aged 32 to 60 years, were randomized in a single-blinded study to receive either undiluted or diluted (1:3.2, 1:10, or 1:32) doses of smallpox vaccine. A comparison group, aged 18 to 31 years, of 10 vaccinia-naive participants received undiluted vaccine. Participants were enrolled between April 1 and May 15, 2002, at the National Institute of Allergy and Infectious Diseases Vaccine and Treatment Evaluation Unit at Saint Louis University, St Louis, Mo. INTERVENTION: Smallpox vaccine was administered by scarification using 15 skin punctures in the deltoid region of the arm. MAIN OUTCOME MEASURES: Presence of a major reaction, defined as a vesicular or pustular lesion or area of palpable induration surrounding a central lesion following vaccination, and measures of viral shedding and antibody titers. RESULTS: Initial vaccination resulted in a major reaction in 64 of 80 non-naive participants. Ninety-five percent of non-naive participants had major reactions in the undiluted group, 90% in the 1:3.2 dilution group, 81% in the 1:10 dilution group, and 52.6% in the 1:32 dilution group. All (n = 10) of the vaccinia-naive participants had major reactions. Compared with vaccinia-naive participants, non-naive participants had significantly smaller skin lesions (P =.04) and significantly less incidence of fever (P =.02). Preexisting antibody was present in 76 of 80 non-naive participants. Antibody responses were significantly higher and occurred more rapidly in the non-naive participants compared with the vaccinia-naive participants (P =.002 for day 28 and P =.003 for 6 months). Vaccinia-naive participants shed virus from the vaccination site 2 to 6 days longer and had significantly higher peak mean viral titers when compared with the non-naive participants (P =.002). CONCLUSIONS: Previously vaccinated persons can be successfully revaccinated with diluted (

[Lymphomatoid papulosis evolving into malignant lymphoma. Clinico-pathological and immunohistochemical study of 3 cases]. / Papulosis linfomatoide con evolución a linfoma maligno. Estudio clinicopatológico e inmunohistoquímico de 3 casos.

Lymphomatoid papulosis is a disorder characterized by recurrent skin lesions with histological features suggestive of malignant lymphoma. In most cases the cutaneous lesions heal spontaneously but the course of the disease is long-lasting and an evolution into a Hodgkin's disease and non-Hodgkin lymphomas may be seen. We report herein the clinical, pathological and immunohistochemical study of three patients having a long-standing lymphomatoid papulosis, which turned into Hodgkin's disease, mycosis fungoides and nodular paragranuloma, respectively. Immunohistochemical analysis showed that the immunophenotype of atypical cells in lymphomatoid papulosis was similar to that observed in Reed-Sternberg cells in Hodgkin's disease and the neoplastic cells of mycosis fungoides. However, the immunohistochemical profile of cells in lymphomatoid papulosis differed from those observed in cells of nodular paragranuloma, developed by one of the three patients. The relationship between lymphomatoid papulosis and malignant lymphomas associated to lymphomatoid papulosis is discussed. The results show that no definitive criteria can be infered from an immunohistochemical study in lymphomatoid papulosis, in predicting the clinical evolution of the disease.

[Evolution of autoantibodies profile in systemic lupus erythematosus according to age and clinical manifestations]. / Profil des réponses auto-anticorps suivant l'âge et la symptomatologie clinique chez des patients atteints de lupus érythémateux.

Clinical features and auto-antibodies profile of 35 Senegalese patients' diagnosed systemic lupus erythematosus (SLE) were analyzed after measurement of antinuclear antibodies (ANA) by IFI, detection of Abs anti-DNA native by ELISA and evaluation of antibodies anti-Sm, anti-RNP, anti-SSA anti-SSB, anti-CCP2, anti-J0, and anti-Scl70 levels by immunodot. Mean age of 33 yrs (18-50 yrs) and sex ratio (F/M) of 16 were found. The most frequent clinical features were rheumatic (88.7%) and cutaneous (79.4%) disorders. ANA and anti-DNAn Abs were detected in 85.7% and 62.5% of the patients respectively. Abs anti-RNP, anti-Sm, anti-SSA, anti-SSB and anti-CCP2 were detected in 30 to 70% of patients. In young patients, the levels of anti-DNAn and anti-Sm Abs were higher than in patients older than 40 yrs (P<0.05). In addition, associations of cutaneous and rheumatic symptoms were characterized by high levels of anti-DNAn, anti-SSA and anti-SSB Abs. Our study shows the interest of a measurement of anti-DNAn, anti-SSA and anti-SSB Abs during the follow of SLE patients particularly in those presenting both rheumatic and cutaneous symptoms.

[Reactivation of the scar of BCG vaccination in Kawasaki's disease: clinical case and literature review]. / Reactivación de la cicatriz de la vacuna BCG en la enfermedad de Kawasaki: caso clínico y revisión de la bibliografía.

Kawasaki disease is an acute febrile multisystemic vasculitis affecting children that can affect the coronary arteries. Routine BCG vaccination in Mexico leads to a 99% coverage in infants younger than 1 year. We present a case of Kawasaki disease with skin lesions at the site of BCG. Clinicians should be aware of this clinical manifestation that could help diagnose atypical or incomplete cases of the disease.

Benign familial Degos disease worsening during immunosuppression.

We describe a 61-year-old woman with skin lesions consistent with those found in Degos disease, both in clinical and in histological appearance. She had had several of these lesions for many years, as had her mother, sister and niece. In 1991, she underwent cadaveric renal transplantation and was treated with immunosuppression: prednisolone, azathioprine and cyclosporin. At that time, she developed many more characteristic skin lesions, and these were slightly larger and more noticeable than those she had had previously. She and the other affected family members appear to fit into the more benign subgroup of Degos disease, and it seems that her immunosuppression aggravated her cutaneous disease.

Benign Degos' disease developing during pregnancy and followed for 10 years.

Degos' disease, or malignant atrophic papulosis, is a rare and often fatal multisystem vasculopathy of unknown etiology. The cutaneous manifestations comprise erythematous papules, which heal to leave scars with a pathognomonic central porcelain-white atrophic area and a peripheral telangiectatic rim. Involvement of the gastrointestinal tract is observed in 50% of cases, with intestinal perforation being the most common cause of death. Other organ systems can also be affected; 20% of cases involve the central nervous system. Systemic manifestations usually develop from weeks to years after onset of skin lesions or, in rare instances, may precede skin lesions. In the patient with Degos' disease reported in this article, the characteristic skin lesions developed during pregnancy, a precipitating event not previously reported. She has survived an unusually long time (10 years) without visceral or neurological involvement, despite florid cutaneous lesions. Moreover, we could detect the presence of antiphospholipid antibodies, the significance of which are currently unclear. These observations therefore confirm that there may be a strictly cutaneous form of Degos' disease with a favourable prognosis.

Benign cutaneous Degos' disease.

We report the case of a 44-year-old woman with Degos' disease who also had a lupus anticoagulant. Electron microscopy of the mature lesions showed interwoven tubular structures within the endothelial cells, as have been observed in previous cases of Degos' disease. Four years after her first cutaneous lesions, there is no evidence of involvement of other organs. Aspirin (300 mg daily) has arrested the cutaneous disease.