Adalimumab induced exacerbation of psoriasis in patients with combined pemphigus: A case report.

RATIONALE: Psoriasis is an immune-related disease caused by genetic factors, abnormalities in the immune system and environmental factors, while pemphigus is an autoimmune disease caused by the autoimmune system attacking the skin and mucosal tissues. Herein, we aimed to report a rare case of adalimumab induced exacerbation of psoriasis patients with pemphigus. The rare disease causes considerable challenges for clinical diagnosis and treatment. PATIENT CONCERNS: The patient was a 43-year-old man with intermittent erythema and scaling all over the body for more than 20 years, and blisters and vesicles on the trunk and limbs for 1 month. Half a year ago, the patient had blisters on the limbs, and was diagnosed with deciduous pemphigus in a hospital, and the blisters subsided after being given traditional Chinese medicine orally. Half a month ago, the erythema area was enlarged, and adalimumab 80 mg intramuscular injection was given for 1 time after consultation in the hospital. On the following day, the area of erythema and scales was suddenly enlarged obviously compared with the previous 1, and obvious blisters and vesicles appeared on the limbs, neck, and trunk, which were aggravated progressively and accompanied by obvious itching and pain. DIAGNOSES: The patient was diagnosed with psoriasis in patients with combined pemphigus. INTERVENTION: After combined treatment with methylprednisolone and cyclosporine, the skin lesions have basically recovered. OUTCOMES: The skin lesions have basically healed. Follow up for 6 months without recurrence. LESSONS: Methylprednisolone combined with cyclosporine may be an option in treating patients with psoriasis patients with pemphigus.

Subjective well-being in patients with pemphigus: a path analysis.

BACKGROUND: Pemphigus is a chronic autoimmune blistering disease of the skin and mucosa severely impairing patients' health-related quality of life (HRQoL). To date, no studies have measured subjective well-being in terms of life satisfaction in pemphigus. Our main objective was to evaluate satisfaction with life in patients with pemphigus, and to analyse its relationship with clinical severity and HRQoL. METHODS: A cross-sectional survey was carried out enrolling 77 patients with pemphigus. Subjective well-being was measured using the Satisfaction with Life Scale (SWLS). HRQoL was assessed by the Dermatology Life Quality Index (DLQI) and EQ-5D-5L. Disease severity was measured by Autoimmune Bullous Skin Disorder Intensity Score (ABSIS). RESULTS: Mean ABSIS, DLQI, EQ-5D-5L and SWLS scores of patients were 11.7 (SD 17.3), 5.4 (6.8), 0.84 (0.22) and 4.76 (SD 1.52), respectively. The proportion of patients indicating extreme dissatisfaction, dissatisfaction, slightly below average in life satisfaction, average satisfaction, high satisfaction and very high satisfaction with life was 6 (7.8%), 5 (6.5%), 14 (18.2%), 16 (20.8%), 21 (27.3%) and 15 (19.5%), respectively. Life satisfaction was independent from age, gender, level of education and type of disease. A path analysis revealed that there was no direct relationship between ABSIS and SWLS (beta = - 0.09; p = 0.428); however, the following indirect path was confirmed: ABSIS → DLQI → EQ-5D-5L → SWLS. CONCLUSIONS: Disease severity and HRQoL measures regularly used to assess patients' health status may be complemented with a measure of subjective well-being, such as SWLS, to achieve a more holistic assessment of patients' lives and optimise pemphigus care.

Diagnostic patterns and delays in autoimmune blistering diseases of the mouth: A cross-sectional study.

OBJECTIVES: To describe the natural history and factors influencing diagnostic delays among patients with autoimmune blistering diseases of the mouth. MATERIALS AND METHODS: In this cross-sectional study, 27 newly diagnosed patients were interviewed, and professional and patient delays were calculated. Disease extent and severity scores were determined using Saraswat scoring system. RESULTS: Twenty-seven patients were interviewed and examined. Patient delay was significantly longer in patients who had desquamative gingivitis as initial presentation, in those who tried to use home remedies and over the counter medications, and in patients with less severe disease. Most patients (n = 21 [77.7%]) made more than one consultation, and the mean time needed to reach a definitive diagnosis (i.e. professional delay) was 83.2 ± 21.4 days (range from 21 to 130 days). Professional delay was significantly correlated with the number of previous consultations (r = .78) and was significantly longer in patients who had desquamative gingivitis as initial presentation. CONCLUSION: Diagnosis of oral blistering diseases is often delayed. Diagnostic delay is more common in patients presenting with desquamative gingivitis and those with less severe disease. Improving patients and healthcare professionals' awareness about oral blistering diseases might help reduce diagnostic delay.

Dapsone in the treatment of pemphigus vulgaris: adverse effects and its importance as a corticosteroid sparing agent.

Pemphigus vulgaris is an autoimmune disease characterized by suprabasal blisters with acantholysis, which has a fatal course in a large number of untreated patients. Systemic corticosteroid therapy is considered first-line therapy. Adjuvant treatment with the goal of sparing corticosteroids include, among others, dapsone. This drug is not without side effects and its use requires clinical and laboratory control. We present a patient with PV initially managed with suboptimal dose of prednisone, evolving into drug-induced hepatitis after introduction of dapsone.

Dapsone in the treatment of pemphigus vulgaris: adverse effects and its importance as a corticosteroid sparing agent

Pemphigus vulgaris is an autoimmune disease characterized by suprabasal blisters with acantholysis, which has a fatal course in a large number of untreated patients. Systemic corticosteroid therapy is considered first-line therapy. Adjuvant treatment with the goal of sparing corticosteroids include, among others, dapsone. This drug is not without side effects and its use requires clinical and laboratory control. We present a patient with PV initially managed with suboptimal dose of prednisone, evolving into drug-induced hepatitis after introduction of dapsone.

Trichosporon inkin as an Emergent Pathogen in Patients With Severe Pemphigus.

IMPORTANCE: To our knowledge, these are the first reports of bloodstream infections by Trichosporon inkin in patients with pemphigus. OBSERVATIONS: Trichosporon inkin, a novel organism causing bloodstream infection, was detected in 2 patients with pemphigus. An elderly man with pemphigus foliaceus died despite treatment with liposomal amphotericin B, 3 mg/kg/d, and a young girl with pemphigus vulgaris responded to treatment with voriconazole, 8 mg/kg/d, for 24 days. One of the T inkin isolates had a minimal inhibitory concentration of 2 mg/L against amphotericin B, suggesting resistance to the drug. CONCLUSIONS AND RELEVANCE: Delayed suspicion of invasive infection by T inkin may result in a poor outcome in patients with severe forms of pemphigus. This opportunistic infection is highly refractory to conventional potent antifungal treatment.

The IgG "lupus-band" deposition pattern of pemphigus erythematosus: association with the desmoglein 1 ectodomain as revealed by 3 cases.

BACKGROUND: Pemphigus foliaceus is an autoimmune skin disease characterized by subcorneal blistering and IgG antibodies directed against desmoglein 1. In the skin, these antibodies deposit intraepidermally. On rare occasions,an additional "lupus band" of granular depositions of IgG and complement is seen along the epidermal basement membrane zone. This combined pattern has been connected with a variant of pemphigus foliaceus named pemphigus erythematosus. OBSERVATIONS: We describe 3 pemphigus foliaceus cases in which phototherapy was administered after a misdiagnosis of psoriasis. This treatment resulted in a flare of skin lesions. Direct immunofluorescence of skin biopsy specimens that were obtained several weeks later demonstrated intraepidermal and granular basement membrane zone depositions. The basement membrane zone depositions consisted of IgG, complement, and the ectodomain of desmoglein 1 and were located below the lamina densa. CONCLUSIONS: High doses of UV light are likely to induce the cleaving of the desmoglein 1 ectodomain. In patients with pemphigus foliaceus, the circulating anti­desmoglein 1 antibodies precipitate this cleaved-off ectodomain along the basement membrane zone, resulting in a lupus band­like appearance. In pemphigus erythematosus, a similar mechanism may be active, which might explain the lupus-band phenomenon.

Low-level laser therapy on the treatment of oral and cutaneous pemphigus vulgaris: case report.

Pemphigus vulgaris is a chronic autoimmune mucocutaneous disease that initially is manifested by painful intraoral erosions and ulcers which spread to other mucosa and the skin, generally more than 5 months after oral lesion manifestation. The treatment consists of prednisone alone or in combination with an immunosuppressive agent, and the clinical response is perceived within 2 to 4 weeks. Low-level laser therapy has been effective in accelerating the healing of injured tissue, thus inducing cell proliferation and increasing ATP, nucleic acid, and collagen synthesis. We reported two cases of pemphigus vulgaris that received systemic treatment associated with low-level laser therapy for oral and cutaneous lesions. We observed prompt analgesic effect in oral lesions and accelerated healing of oral and cutaneous wounds. Therefore, the present report suggests LLLT as a noninvasive technique that should be considered as an adjuvant therapy in oral and skin disorders in patients with PV.

Pemphigus erythematosus in a chow chow.

A 3.5-year-old, spayed female, chow chow presented with a pruritic, ulcerative, butterfly lesion on the nasal planum, typical of the pemphigus complex. Pemphigus erythematosus was diagnosed by histopathologic examination. Treatment consisted of enrofloxacin and immunosuppressive therapy with prednisone and azathioprine. Within 5 wk of treatment, the lesions had resolved almost completely.

Intravenous immunoglobulin therapy for patients with pemphigus foliaceus unresponsive to conventional therapy.

BACKGROUND: Pemphigus foliaceus (PF) is a chronic autoimmune blistering skin disease that is commonly treated with oral corticosteroids and immunosuppressive therapy. In some patients, PF can be refractory to treatment and the resultant side effects of prolonged immune suppression can be potentially fatal. Alternative therapies are needed. OBJECTIVE: The purpose of this study is to report treatment outcomes with IVIg therapy in 11 patients with severe PF refractory to prednisone and other immunosuppressive therapy. METHODS: Selection criteria included documentation of a biopsy and immunopathology in 11 patients who were resistant to treatment or experienced side effects to conventional therapy. IVIg was administered according to a defined protocol. The parameters used to assess clinical response to IVIg included time observed for effective control of disease, duration of IVIg maintenance therapy, total duration of IVIg, number of IVIg cycles, systemic drug therapy, and the frequency of recurrences and relapses. The pre-IVIg and post-IVIg data were statistically analyzed by means of the SAS UNIVARIATE and 2-sided Wilcoxon sign rank and sign tests. RESULTS: All patients had an effective clinical response and remained in clinical remission for a mean period of 18.6 months after discontinuation of IVIg therapy. Serious side effects from IVIg use were not observed. CONCLUSION: IVIg therapy appears to have potential as a biologic alternative agent in inducing and maintaining clinical remissions in patients with PF who are resistant to more standard conventional treatment. IVIg is effective as monotherapy and may be needed for a period of several months to achieve a long-term clinical remission.

Intravenous immunoglobulin therapy in the treatment of patients with pemphigus vulgaris unresponsive to conventional immunosuppressive treatment.

BACKGROUND: Severe pemphigus vulgaris (PV) is conventionally treated with high-dose oral prednisone, usually in combination with an immunosuppressive agent (ISA). Some patients experience significant side effects, which are sometimes fatal, from prolonged immunosuppression. OBJECTIVE: Intravenous immunoglobulin (IVIg) was administered to 21 patients with severe cutaneous and mucosal PV who had not responded to the prolonged use of oral prednisone and multiple ISAs. METHODS: A preliminary dose-determination study tested 7 additional volunteers to ascertain the optimal IVIg dose of 2 g/kg per cycle. Parameters to assess clinical outcome were recorded before and after IVIg therapy. Variables tested were highest dose, total dose, and duration of prednisone and ISAs, their side effects, frequency of recurrence and relapse, duration of IVIg therapy, clinical response, induction and duration of remission, number of hospitalizations, total days of hospital stay, and quality of life. RESULTS: Use of IVIg monotherapy resulted in effective control of disease and produced a sustained remission in the 21 patients. The patients became free of lesions and remained so after finishing IVIg therapy. IVIg had a steroid-sparing effect and produced a high quality of life. Serious side effects from the use of IVIg were not observed. IVIg needs to be gradually withdrawn after achievement of clinical control. CONCLUSION: In patients with PV who do not respond to conventional immunosuppressants, IVIg appears to be an effective treatment alternative. Its early use is of significant benefit in patients who may experience life-threatening complications from immunosuppression. IVIg is effective as monotherapy.

Pemphigus vulgaris antibody identifies pemphaxin. A novel keratinocyte annexin-like molecule binding acetylcholine.

Because pemphigus vulgaris (PV) IgGs adsorbed on the rDsg3-Ig-His baculoprotein induced blisters in neonatal mice, it was proposed that anti-desmoglein 3 (Dsg 3) autoantibody causes PV. However, we found that rDsg3-Ig-His absorbs autoantibodies to different antigens, including a non-Dsg 3 keratinocyte protein of 130 kDa. This prompted our search for novel targets of PV autoimmunity. The PV IgG eluted from a 75-kDa keratinocyte protein band both stained epidermis in a pemphigus-like pattern and induced acantholysis in keratinocyte monolayers. Screening of a keratinocyte lambdagt11 cDNA library with this antibody identified clones carrying cDNA inserts encoding a novel molecule exhibiting approximately 40% similarity with annexin-2, named pemphaxin (PX). Recombinant PX (rPX-His) was produced in Escherichia coli M15 cells, and, because annexins can act as cholinergic receptors, its conformation was tested in a cholinergic radioligand binding assay. rPX-His specifically bound [(3)H]acetylcholine, suggesting that PX is one of the keratinocyte cholinergic receptors known to be targeted by disease-causing PV antibodies. Preabsorption of PV sera with rPX-His eliminated acantholytic activity, and eluted antibody immunoprecipitated native PX. This antibody alone did not cause skin blisters in vivo, but its addition to the preabsorbed PV IgG fraction restored acantholytic activity, indicating that acantholysis in PV results from synergistic action of antibodies to different keratinocyte self-antigens, including both acetylcholine receptors and desmosomal cadherins.

Graft-versus-host disease-like immunophenotype and apoptotic keratinocyte death in paraneoplastic pemphigus.

Paraneoplastic pemphigus (PP) is an autoimmune disease, which is frequently associated with non-Hodgkin's lymphoma. Autoantibodies against components of the cytoplasmic plaque of epithelial desmosomes are usually present in the sera and are believed to play a major pathogenic part in acantholysis and suprabasal epidermal blistering. However, another typical histological feature of PP, interface dermatitis with keratinocyte dyskeratosis, is shared with skin diseases that involve epithelial damage mediated by T cells. Here, we present the detailed characterization of the cutaneous T-cell response in a patient with PP and demonstrate a selective epidermal accumulation of activated CD8+ T cells together with an increased local production of interferon-gamma and tumour necrosis factor-alpha, and a strong expression of HLA-DR and ICAM-1 on keratinocytes. Apoptosis was identified as a key mechanism of keratinocyte death, and appeared independent of the FAS/FAS ligand (FAS-L) pathway, as epidermal expression of FAS was not increased compared with normal skin, and FAS-L was undetectable on the protein and mRNA level. Triple therapy with high-dose corticosteroids, cyclophosphamide and intravenous immunoglobulins reduced levels of pemphigus-like autoantibodies and reversed the cutaneous inflammatory reaction leading to long-standing clinical remission. Our findings support the concept of a major contribution of cytotoxic T lymphocytes to the immunopathology of paraneoplastic pemphigus.

[D-penicillamine-induced pemphigus, polymyositis and myasthenia]. / Pemphigus, polymyosite et myasthénie induits par la D-pénicillamine.

BACKGROUND: D-penicillamine can induce autoimmune disease, particularly in patients with associated immune disorders. CASE REPORT: A 67-year old woman who had been taking D-penicillamine for 15 months for rheumatoid arthritis was hospitalized due to the development of a bullous eruption and proximal muscle deficiency. Search for intercellular antisubstance antibodies in serum was negative. The skin biopsy histology revealed intra-epidermal cleavage in the mucosal body and direct immunofluorescence revealed epidermal frame-marking with anti-IgG and anti-C3 antibodies. Other tests revealed muscular cytolysis, and anti-acetylcholine receptor antibodies. The electromyogram showed neuromuscular block without muscle deficiency and muscle biopsy showed moderate myositis. D-penicillamine was interrupted and was followed by cure of the pemphigus and aggravation of the myositis, requiring high-dose systemic corticosteroid therapy. DISCUSSION: This patient developed D-penicillamine induced pemphigus, a rather frequent observation. The desmoglein immunolabelling favored drug-induced pemphigus and the course was rapidly favorable after withdrawal. Pemphigus had developed simultaneously with signs of myasthenia and polymyositis. Polymyositis and myasthenia are also known complications of D-penicillamine therapy. The association of these three complications suggests that D-penicillamine can unmask certain antigens or have an immunomodulator effect.

Pemphigus and pemphigoid-like effects of nifedipine on in vitro cultured normal human skin explants.

BACKGROUND: A variety of drugs have been implicated in the onset and exacerbation of pemphigus and bullous pemphigoid. The demonstration of biochemical acantholysis in skin explants to various drugs in the absence of autoantibodies, in which the tested drugs evoke a biochemical reaction that leads to desmosomal function loss, may be a valuable adjunct to patient management by confirming the suspicion of drug-related pemphigus or bullous pemphigoid. OBJECTIVE: To determine whether a skin explant model might serve as a possible in vitro correlate of drug-induced pemphigus and pemphigoid-like effects related to the calcium channel blocker nifedipine. METHODS: Normal human breast skin obtained from nonpemphigus and nonpemphigoid patients undergoing mastectomy was cultured with nifedipine at final concentrations of 2, 4, and 8 mM. The drug effect on skin explants evidenced by morphologic changes was evaluated by microscopy by three observers. RESULTS: Five out of seven explants cultured with nifedipine at concentrations ranging from 2 to 8 mM exhibited obvious morphologic changes of two types: intraepithelial (or pemphigus-type) splittings and subepithelial (or pemphigoid-type) splittings. Two explants showed no acantholysis and no subepithelial splittings. Control cultures without polyethylene glycol 200 (PEG) showed no changes. Skin control samples cultured in medium supplemented with 10% PEG displayed vacuolar degeneration throughout the entire epidermis, but no sign of cell-cell dyshesion or dermo-epidermal detachment. CONCLUSIONS: A type of skin susceptibility to nifedipine may be genetically determined, with some nifedipine-treated patients developing an acantholytic reaction and others a subepidermal bullous eruption.

Proteinase inhibitors and pemphigus vulgaris. An in vitro and in vivo study.

The aim of this study was to determine the inhibitory effect of clinically usable proteinase inhibitors p-aminomethylbenzoic acid (PAMBA), and aprotinin on acantholysis in skin organ culture and in clinical trials with pemphigus patients. PAMBA added to the culture medium at a concentration of 1 mg/ml fully prevented the acantholysis, while Contrykal at 10 ATrE/ml reduced acantholysis. Subsequently, we treated 12 patients (groups 1) with PAMBA 100-200 mg daily for 7 to 26 days in combination with a moderate dose of corticosteroid (mean dose 36.1 mg prednisolone equivalent) or immunosuppressive drugs. A second group of 12 patients (group 2) were treated with a high dose of corticosteroid (mean 94.2 mg prednisolone equivalent) and immunosuppressive drugs. Evaluation was performed before treatment, after 3 weeks and on discharge using a clinical scoring system. The inclusion of PAMBA in the treatment protocol of group 1 resulted in active disease being brought under control with lower corticosteroid doses. As a result, fewer side effects were observed in group 1 than in group 2. In our opinion, protease inhibitors may be useful as adjuvant drugs in the combination therapy of pemphigus.