Clinicopathologic features of IgG/IgA pemphigus in comparison with classic (IgG) and IgA pemphigus.

BACKGROUND: The pemphigus group is characterized by the presence of circulating immunoglobulins against desmosomes. IgG/IgA pemphigus is defined by the presence of IgG and IgA cell surface deposits upon direct immunofluorescence (DIF) and/or circulating IgG and IgA autoantibodies upon indirect immunofluorescence. Previous reports of patients with IgG/IgA pemphigus are sparse. Whether IgG/IgA pemphigus is best classified as a subtype of IgG (classic) pemphigus or IgA pemphigus, or as a distinct entity, has yet to be determined. OBJECTIVES: We compared the features of patients with IgG/IgA pemphigus to those of IgG pemphigus and IgA pemphigus. METHODS: Retrospective clinicopathologic study of patients with IgG, IgG/IgA, and IgA pemphigus evaluated at our clinic (1993-2013). RESULTS: We included 26, 13, and seven patients with IgG, IgG/IgA, and IgA pemphigus, respectively. Patients with IgG/IgA pemphigus did not differ significantly from patients with IgG pemphigus in terms of clinical and microscopic features, DIF findings, anti-desmoglein antibody values, and treatments required. However, patients with IgG/IgA pemphigus were significantly different from patients with IgA pemphigus regarding intertriginous distribution (P = 0.038) and pustular lesions (P < 0.001), acantholysis (P = 0.043), and presence of intercellular C3 deposits on DIF (P < 0.001). CONCLUSION: Comparative clinicopathologic data imply that IgG/IgA pemphigus may best be regarded as a variant of IgG pemphigus and distinct from IgA pemphigus.

Assessment of the therapeutic benefit of oral prednisolone and common adjuvant therapy in stage II of randomized controlled trial study for management of pemphigus vulgaris.

BACKGROUND: Pemphigus is an autoimmune blistering mucocutaneous disorder. Common treatments include corticosteroids and immunosuppressive drugs. This study aimed to assess the therapeutic effects of oral prednisolone along with the common adjuvant therapy in pemphigus vulgaris. METHODS:   Eighty-seven patients with pemphigus vulgaris from the first stage of a previously randomized clinical trial were enrolled in the present non-blinded clinical trial. The patients were divided into four groups and treated accordingly with prednisolone alone (P; N = 23), prednisolone and azathioprine (P/A; N = 23), prednisolone and mycophenolate mofetil (P/M; N = 21), and prednisolone and cyclophosphamide (P/C; N = 20). These patients were followed-up for an extended one-year period. RESULTS: The primary localization of the recurrence occurred in the oral cavity of 7, 6, 2, and 5 patients in the P, P/A, P/M, and P/C groups, respectively. There was no significant difference between them (P = 0.40). The mean total dose of prednisolone administered in groups P, P/A, P/M, and P/C was accordingly 7.5, 8.4, 9.2, and 8.6 mg/day. Minor recurrence of the disease in the above-mentioned groups was observed in 7 (30.4%), 5 (21.7%), 6 (28.6%), and 7 (35.0%) of the patients, respectively. With regard to the minor recurrence of the disease, there was no significant difference among the four treatment groups (P = 0.80). CONCLUSION: Since in this follow-up study no therapeutic benefit of oral prednisolone and common adjuvant therapy was found in terms of the number of minor and major recurrences, the extent to which treatment of PV can be improved upon treatment with these agents remains to be elucidated.

Vitiligo-inducing phenols activate the unfolded protein response in melanocytes resulting in upregulation of IL6 and IL8.

Vitiligo is characterized by depigmented skin patches caused by loss of epidermal melanocytes. Oxidative stress may have a role in vitiligo onset, while autoimmunity contributes to disease progression. In this study, we sought to identify mechanisms that link disease triggers and spreading of lesions. A hallmark of melanocytes at the periphery of vitiligo lesions is dilation of the endoplasmic reticulum (ER). We hypothesized that oxidative stress results in redox disruptions that extend to the ER, causing accumulation of misfolded peptides, which activates the unfolded protein response (UPR). We used 4-tertiary butyl phenol and monobenzyl ether of hydroquinone, known triggers of vitiligo. We show that expression of key UPR components, including the transcription factor X-box-binding protein 1 (XBP1), is increased following exposure of melanocytes to phenols. XBP1 activation increases production of immune mediators IL6 and IL8. Co-treatment with XBP1 inhibitors reduced IL6 and IL8 production induced by phenols, while overexpression of XBP1 alone increased their expression. Thus, melanocytes themselves produce cytokines associated with activation of an immune response following exposure to chemical triggers of vitiligo. These results expand our understanding of the mechanisms underlying melanocyte loss in vitiligo and pathways linking environmental stressors and autoimmunity.

Intravenous immunoglobulin in the treatment of autoimmune bullous dermatoses: an update.

High-dose intravenous immunoglobulin (IVIg) is being increasingly utilized as an off-label therapy for a variety of autoimmune and inflammatory conditions across various specialties. Numerous reports have shown that it is an effective treatment for autoimmune skin blistering disorders. Unlike most therapies for blistering disorders, IVIg is not immunosuppressive and has a favorable side effect profile. This has allowed its use to expand dramatically over the last decade. However, due to the rarity and severity of autoimmune skin blistering diseases, well-designed prospective trials are generally lacking. This work highlights major research developments and the best evidence to date regarding the treatment of autoimmune pemphigus, bullous pemphigoid, mucous membrane pemphigoid, epidermolysis bullosa acquisita, pemphigoid gestationis, and linear IgA dermatosis with IVIg, providing an update on its efficacy, proposed mechanisms of action, side effect profile, and indications for use.

Effect of intravenous immunoglobulin with or without cytotoxic drugs on pemphigus intercellular antibodies.

BACKGROUND: Intravenous immunoglobulin (IVIg)--a relatively new approach to treat pemphigus--lowers serum levels of pemphigus antibodies; however, the optimal way to use this agent is unknown. OBJECTIVE: We sought to examine whether coadministration of a cytotoxic drug to patients with pemphigus improves the ability of IVIg to decrease serum levels of intercellular (IC) antibodies. METHODS: In this retrospective study, we analyzed changes in IC antibody levels in 20 patients with pemphigus who were treated with 24 courses of IVIg administered alone (n = 10) or with a cytotoxic drug (n = 14). Each course of IVIg consisted of 400 mg/kg daily of immunoglobulin given over 5 days every other week; this cycle was repeated 3 to 4 times. Serum levels of IC antibodies were measured at baseline, before treatment, and 1 week and 1 month after the last IVIg cycle. RESULTS: One week after the last IVIg cycle IC antibodies decreased by an average of 77% in the group treated with IVIg and cytotoxic drug compared with 48% in the group treated with IVIg alone (P = .54), and by 90% versus 43% 1 month later (P = .03). LIMITATIONS: A larger sample size is suggested for future studies. CONCLUSIONS: These observations confirm that IVIg can rapidly lower serum levels of autoantibodies in patients with pemphigus and its ability to do so is improved by the coadministration of a cytotoxic drug. These findings imply that the clinical effectiveness of IVIg in treating pemphigus, and possibly other autoantibody-mediated diseases, may be improved by the concurrent administration of a cytotoxic drug.

The comparison between the efficacy of high dose acyclovir and erythromycin on the period and signs of pitiriasis rosea.

BACKGROUND: Pityriasis Rosea (PR) is an acute inflammatory and self-limiting skin disorder, sometimes with troublesome symptoms. To date, there are few treatments available for this disorder. AIM: Compare the traditional treatment with erythromycin to a newly introduced antiviral treatment acyclovir for PR. MATERIALS AND METHODS: Patients with clinically confirmed diagnosis of PR, matching our exclusion criteria, were enrolled. They were randomized in two groups that received high-dose oral acyclovir or erythromycin. The participants were evaluated two, four, and eight weeks after commencement of the study and followed for one year. RESULTS: A total of 30 patients including 15 males and 15 females completed the study. After eight weeks, 13 patients in the acyclovir group experienced complete response, while in the erythromycin group only six patients had complete response (P < 0.05). Also, patients in the acyclovir group experienced faster resolution of pruritus in comparison with the erythromycin group (not significant). No adverse drug reaction was detected in both groups. CONCLUSION: It seemed that a high-dose of oral acyclovir was a safe and effective therapy for PR, although this remained to be confirmed in larger studies.

Potential role of interleukin-17 in the pathogenesis of bullous pemphigoid.

Bullous pemphigoid is an autoimmune blistering disease of the skin caused by autoantibodies directed against basement membrane zone adhesion molecules. Autoantibodies cannot fully explain several important features of the disease such as the difficulty transferring with the pathogenic autoantibodies, or the presence of heavy lesional infiltration of eosinophils and neutrophils that is necessary for disease production. There is increasing evidence that Th17 cells and the cytokines they release such as interleukin-17 are important regulators of innate and adaptive immune responses in many Th1 and/or Th2 mediated autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and allergic asthma. There is also evidence that Th17 cells have a role in pathogenesis of blistering skin diseases. Interleukin-17 is important in initiation and maintenance of many autoimmune reactions and it is involved in production of pro-inflammatory cytokines, matrix metalloproteinases, neutrophils, and eosinophils, all of which are important pathogenic factors in bullous pemphigoid. The hypothesis is that interleukin-17 has an important pathogenic role in BP and can describe features of the disease not explained by the autoantibody theory. This cytokine can be assessed in the blister fluid and sera of patients, and can be used as a marker of disease activity and response to therapy. The information obtained could also lead to the development of novel therapeutic strategies for this and other autoimmune blistering diseases.

Pemphigus vulgaris in Iran: a clinical study of 140 cases.

BACKGROUND: Pemphigus vulgaris (PV) is a rare autoimmune blistering disease of the skin and mucous membranes. It varies in its clinical profile and epidemiologic characteristics in different parts of the world. OBJECTIVE: To determine the clinical features of PV in Iran in a prospective manner. METHODS: The study included 140 patients with newly registered PV attending our dermatology clinic between January 2003 and June 2004. RESULTS The mean age at the onset of the disease was 41.5 +/- 15.7 years, with a female to male ratio of 1.59 : 1. At presentation to our clinic, both skin and mucosal involvement was observed in 95 patients (67.9%). Cutaneous lesions without the involvement of the mucous membranes were seen in nine patients (6.4%), and exclusive mucosal involvement was present in 36 patients (25.7%). The most common initial localization of the disease was the oral cavity, which was involved in 93 patients (77.5%). The most frequent cutaneous and mucosal sites involved were the thorax and oral cavity, respectively. CONCLUSION: Although minor differences were noted, the results of this study are in relatively good agreement with the literature with regard to the age, gender, and initial presentation of PV in Iran. Some skin sites, such as the scalp, thorax, and axilla, may be more commonly affected in men. Patients with initial mucosal lesions were significantly younger than those with initial cutaneous involvement. Mucosal lesions other than the oral mucosa may be more common than previously thought.

Isotretinoin in acne agminata.

Acne agminata is an asymptomatic papulopustular eruption. This condition typically occurs in young adults. The eruption generally runs a self-limited course, but disfiguring scars can occur. Histological examination shows scattered dermal granulomas composed of epitheloid and some giant cells with central caseation. A variety of agents such as wide-spectrum antibiotics, oral steroids, dapsone, and clofazimine have been used with varying degrees of success. Herein, we report 2 Caucasian males with acne agminata, successfully treated with isotretinoin.

KID syndrome.

KID syndrome is a rare congenital disorder characterized by keratitis, ichthyosis, and deafness. We have described a 4-year-old girl who is treated with bland emollients and topical keratolytics such as urea and surprisingly observed marked improvement in skin hyperkeratosis and palmoplantar keratoderma. We think that along with urgent ophthalmologic and otolaryngologic measures, simple topical therapies may improve skin condition in KID syndrome precluding the possible hazards of systemic retinoid therapy.

Bilateral cutaneous leishmaniasis of upper eyelids: a case report.

An 11-year-old girl presented with a 6-month history of bilateral upper eyelid erythema, induration, and blepharitis resistant to conventional antibiotic therapy. The lesions gradually progressed to symmetrical ulcerative nodules within 3 months. Cutaneous smear and biopsy revealed numerous amastigotes in macrophage cells. Therapy with systemic pentavalent antimonial resulted in successful healing of lesions. We conclude that cutaneous leishmaniasis must be kept in mind in the differential diagnosis of bilateral chronic eyelid swelling in endemic regions of the world.

Koebner phenomenon in xanthelasma after treatment with trichloroacetic acid.

A 47-year-old woman presented with a history of yellow plaques on her eyelids. These lesions had been diagnosed clinically as xanthelasma and treated five times with topical applications of trichloroacetic acid (TCA) 33 percent. Despite flattening of the original lesions, the patient noticed extension of the lesions on the site of treatment following each session. Skin biopsy showed characteristic findings of xanthelasma. It appears that, in rare instances, xanthelasma palpebrarum may progress following TCA application by a Koebner-like phenomenon.

Erythroderma: a clinical study of 97 cases.

BACKGROUND: Erythroderma is a rare skin disorder that may be caused by a variety of underlying dermatoses, infections, systemic diseases and drugs. METHODS: We reviewed the clinical, laboratory and biopsy material of 97 patients diagnosed with erythroderma who were treated in our department over a 6-year period (1996 through 2002). RESULTS: The male-female ratio was 1.85:1. The mean age at diagnosis was 46.2 years. The most common causative factors were dermatoses (59.7%), followed by drug reactions (21.6%), malignancies (11.3%) and idiopathic causes (7.2%). Carbamazepine was the most common drug (57.1%). The best clinicopathologic correlation was found in cutaneous T-cell lymphoma and pityriasis rubra pilaris related erythroderma. Apart from scaling and erythema that were present in all patients, pruritus was the most common finding (97.5%), followed by fever (33.6%), lymphadenopathy (21.3%), edema (14.4%) and hyperkeratosis (7.2%). CONCLUSION: This study outlines that underlying etiologic factors of erythroderma may show geographic variations. Our series had a high percentage of erythroderma secondary to preexisting dermatoses and a low percentage of idiopathic cases. There was no HIV-infected patient among our series based on multiple serum antibody tests. The clinical features of erythroderma were identical, irrespective of the etiology. The onset of the disease was usually insidious except in drug-induced erythroderma, where it was acute. The group associated with the best prognosis was that related to drugs.