mycophenolic-acid and Pemphigoid--Bullous

We propose rituximab as a first-line therapy for pemphigus vulgaris and steroid-dependent bullous pemphigoid with or without systemic steroids. A brief review of the literature substantiates the significant risk associated with the use of long term, high-dose prednisone, mycophenolate mofetil (MMF), and azathioprine. No head-to-head studies are available with respect to safety and efficacy of rituximab versus these therapies. When comparing the side effects of rituximab to MMF, both are found to be mild when used as monotherapy in dermatologic patients. The most severe side effects of rituximab include fatal infusion reactions and hypersensitivity, pancytopenia, infection and organ dysfunction. With MMF, malignancy, pancytopenia, infection, and organ dysfunction are the most concerning side effects. The frequencies of these observed adverse events are difficult to compare, but the side effect profiles of rituximab and MMF are clearly similar. Therefore, there is equipoise whether to use rituximab before rather than after MMF and/or systemic corticosteroids.

Topics: Antibodies, Monoclonal, Murine-Derived; Azathioprine; Glucocorticoids; Humans; Immunologic Factors; Immunosuppressive Agents; Mycophenolic Acid; Pemphigoid, Bullous; Prednisone; Rituximab

Bullous pemphigoid (BP) is the most common auto-immune bullous disorder. Its treatment is difficult due to high age and comorbidities of affected patients.. To assess the effects of treatments for BP.. Randomized therapeutic trials (RCTs) were identified using an automatic search on Pubmed et Embase until March 2009. Large retrospective series with homogeneous therapeutic management were also selected and analyzed.. Forty-four articles were selected and analyzed, which included nine RCTs with a total of 1007 participants (653 patients were included in two trials). Two RCTs comparing different modalities of systemic corticosteroid therapy failed to show differences in measure of disease control. The addition of plasma exchanges (one RCT) or azathioprine (one RCT) allowed to halve the amount of prednisone required for disease control. A further 3-arms RCT compared plasma exchange or azathioprine plus prednisone, but failed to show significant differences for disease control or mortality of BP. One study compared tetracycline plus nicotinamide with prednisolone, no significant difference for disease response was evidenced. A large controlled clinical trial demonstrated that high doses of very potent topical corticosteroids increased initial disease control and 1-year survival of patients with extensive BP, as compared with oral prednisone. Another RCT compared two regimens of potent topical corticosteroids and a non-inferior rate of BP control was obtained with the mild regimen. Finally, a study comparing two immunosuppressant drugs (azathioprine, mycophenolate mofetil) in addition to prednisone failed to show any difference for disease control, recurrence rate or the cumulated doses of prednisone.. Ultrapotent topical corticosteroids (clobetasol propionate; 20 to 40g/day) are effective treatments for BP with fewer systemic side-effects than oral high-dose corticosteroids. Systemic corticosteroids are effective but doses greater than 0.5mg/kg per day are associated with severe side-effects, including decreased survival. The effectiveness of the addition of plasma exchange or immunosuppressants (azathioprine, mycophenolate mofetil) to systemic corticosteroids has not been established. Combination treatment with tetracycline and nicotinamide needs further validation.

Topics: Aged; Azathioprine; Clobetasol; Combined Modality Therapy; Dapsone; Dose-Response Relationship, Drug; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Meta-Analysis as Topic; Multicenter Studies as Topic; Mycophenolic Acid; Niacinamide; Pemphigoid, Bullous; Plasma Exchange; Prednisone; Randomized Controlled Trials as Topic; Recurrence; Retrospective Studies; Tetracycline

Bullous pemphigoid is the most frequent autoimmune bullous skin disease and affects subjects who are about 80 years old. The risk factors are neurological degenerative diseases, poor Karnovski's status and some drugs (aldactone and neuroleptics). Typically, the disease consists of itching eczematous or urticarial sheets, surmounted by blisters. The blisters heal without scars. Mouth and head are rarely involved. The diagnostic is made by histological examination . It shows a subepidermal blister with some degree of dermal infiltrate with lymphocytes and eosinophils. Direct immunofluorescence reveals a linear pattern of IgG deposition along the basal membrane, which signs the diagnosis. Indirect immunofluorescence detecting anti-basal membrane antibodies is of poor diagnostic value. New tests detecting BPAg 2 antibodies by enzyme-linked immunosorbant assay (ELISA) seems to be good markers for disease activity and prognosis. Recommended treatment is topical corticosteroids (clobetasol propionate cream) for several months. It has been showed to be more effective and less dangerous than oral corticotherapy in severe forms of bullous pemphigoid. Corticosteroid sparing agents like methotrexate or mycophenolate mofetil are sometimes used because of cutaneous or systemic side effect of strong and protracted topical corticosteroid therapy. The management of these patients shall be done by specialized and coordinated staff in order to bring the best care.

Topics: Anti-Inflammatory Agents; Autoantigens; Clobetasol; Collagen Type XVII; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique, Direct; France; Histological Techniques; Humans; Immunoglobulin G; Immunosuppressive Agents; Karnofsky Performance Status; Methotrexate; Mycophenolic Acid; Non-Fibrillar Collagens; Patient Care Team; Pemphigoid, Bullous; Prognosis; Risk Factors

Bullous pemphigoid is an autoimmune skin blistering disorder that can present with several different degrees of severity. The treatment modality employed by the treating physician varies from localised topical therapy and anti-inflammatory treatments with minimal side effects to immunosuppressive agents associated with significant adverse reactions. Deciding which therapy to use with a particular patient can be a challenge, and the treating physician must take into account the severity of disease, the overall medical condition of the patient and potential drug interactions. This article provides a comprehensive review of current medical therapies, as well as an overall approach to the patient with bullous pemphigoid.

Topics: Administration, Topical; Anti-Inflammatory Agents; Antibodies, Monoclonal; Azathioprine; Cyclophosphamide; Glucocorticoids; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Mycophenolic Acid; Pemphigoid, Bullous; Plasmapheresis

To investigate the safety and efficacy of oral methylprednisolone combined with azathioprine sodium or mycophenolate mofetil for the treatment of bullous pemphigoid.. A prospective, multicenter, randomized, nonblinded clinical trial to compare 2 parallel groups of patients with bullous pemphigoid undergoing different treatments.. Thirteen departments of dermatology in Germany.. Patients with bullous pemphigoid (n = 73) as evidenced by clinical lesions suggestive of bullous pemphigoid, signs of subepidermal blistering on histologic analysis of skin biopsy specimens, linear deposition of IgG and C3 along the dermoepidermal junction, and deposition of autoantibodies at the blister roof in split-skin analysis.. Treatment with oral methylprednisolone plus azathioprine (azathioprine group) or oral methylprednisolone plus mycophenolate mofetil (mycophenolate mofetil group).. The cumulative total methylprednisolone doses and rates of remission. Secondary outcome measures were safety profiles and duration of remission.. In 38 of 38 patients in the azathioprine group (100%), complete remission was achieved after a mean +/- SD of 23.8 +/- 18.9 days vs 42.0 +/- 55.3 days for 35 of 35 patients in the mycophenolate mofetil group (100%). In the azathioprine group, the median +/- SD total cumulative methylprednisolone dose used was 4967.0 +/- 12 190.7 mg vs 5754.0 +/- 9692.8 mg in the mycophenolate mofetil group. Nine of 38 patients in the azathioprine group (24%) experienced grade 3 or 4 adverse effects vs 6 of 35 patients in the mycophenolate mofetil group (17%). Azathioprine therapy induced significantly elevated liver function test results compared with mycophenolate mofetil (P < .001). Importantly, patients in the azathioprine group showed significantly higher toxicity grades for aspartate aminotransferase (P = .03), alanine aminotransferase (P = .03), and gamma-glutamyltransferase (P = .01) than did those in the mycophenolate mofetil group.. Mycophenolate mofetil or azathioprine demonstrate similar efficacy during treatment of bullous pemphigoid, and similar cumulative corticosteroid doses were given in both treatment arms to control disease. However, mycophenolate mofetil showed a significantly lower liver toxicity profile than azathioprine therapy.

Topics: Administration, Oral; Adrenal Cortex Hormones; Aged; Aged, 80 and over; Azathioprine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Methylprednisolone; Middle Aged; Mycophenolic Acid; Patient Compliance; Pemphigoid, Bullous; Recurrence; Remission Induction

Topics: Eye; Humans; Immunosuppressive Agents; Mucous Membrane; Mycophenolic Acid; Pemphigoid, Benign Mucous Membrane; Pemphigoid, Bullous

The first-line treatment for patients with bullous pemphigoid (BP), the most common autoimmune blistering disease, is systemic glucocorticoids, which are associated with numerous side effects. Mycophenolate mofetil (MMF) may be beneficial in BP as a steroid-sparing alternative; however, evidence is limited.. To evaluate the efficacy and safety of MMF in patients with BP.. In this retrospective chart review, records of patients with BP treated with MMF alone or in combination with prednisone, who presented between 2013 and 2017, were analyzed.. Twenty-six patients were included. Twelve patients were treated with MMF alone (monotherapy) and fourteen were treated with MMF and prednisone concomitantly at some point during their treatment course (dual therapy). Improvement in BP was observed in 26 (100%) patients with MMF therapy. Mean time to improvement was 0.8 months. Twenty-five (96.2%) patients [11/12 (91.7%) on monotherapy and 14/14 (100%) on dual therapy] achieved complete control of their disease. Mean time to complete control amongst all patients was 5.6 months. Twelve (46.2%) patients [4/12 (33.3%) on monotherapy and 8/14 (57.1%) on dual therapy] experienced disease remission with no subsequent flares for up to 15 months after MMF was discontinued. Twelve mild adverse effects were reported with one individual discontinuing therapy due to gastrointestinal symptoms. No serious adverse effects were reported.. MMF is a safe and effective therapy for BP and can yield improvement and complete response in most patients and remission in some. J Drugs Dermatol. 2022;21(2):151-155. doi:10.36849/JDD.6042.

Topics: Drug Therapy, Combination; Humans; Immunosuppressive Agents; Mycophenolic Acid; Pemphigoid, Bullous; Prednisone; Retrospective Studies; Treatment Outcome

Bullous pemphigoid is rarely seen in adolescence, and its presentation, clinical course, and treatment can differ to that found in other age groups. We present a case of bullous pemphigoid in a 16-year-old with features of koebnerisation and oral mucosal involvement and provide a brief review of paediatric bullous pemphigoid.

Topics: Adolescent; Anti-Inflammatory Agents; Antibiotics, Antitubercular; Betamethasone; Female; Glucocorticoids; Humans; Methylprednisolone; Mycophenolic Acid; Pemphigoid, Bullous; Prednisone

Topics: Hemophilia A; Humans; Immunosuppressive Agents; Mycophenolic Acid; Omalizumab; Pemphigoid, Bullous

Topics: Administration, Cutaneous; Administration, Oral; Adult; Aged; Aged, 80 and over; Autoimmune Diseases; Cyclosporine; Disease Management; Enzyme Inhibitors; Female; Glucocorticoids; Humans; Hydroxyurea; Immunosuppressive Agents; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Pemphigoid, Bullous; Pemphigus; Psoriasis; Retrospective Studies; Ultraviolet Therapy

Mucous membrane pemphigoid (MMP) is a rare variant of the skin disease pemphigoid, which predominantly involves the mucous membranes. This rare autoimmune disease that infrequently affects the respiratory tract is characterized by subepithelial blister formation that may result in scarring. Immunopathologic examination of mucous membranes reveals the deposition of immunoglobulins and complement within the subepithelial basement membrane. We describe a patient with undiagnosed MMP, with a near-fatal presentation of central airway obstruction causing acute respiratory distress. The patient was successfully treated with emergent rigid bronchoscopic resection of a ball valve-like endotracheal mass, and diagnosed with a rare variant of pemphigoid disease, MMP. The patient was treated with mycophenolate and was clinically in remission, with bronchoscopically stable lesions at 1 year of follow-up.

Topics: Airway Obstruction; Antibiotics, Antineoplastic; Bronchoscopy; Female; Humans; Mucous Membrane; Mycophenolic Acid; Pemphigoid, Benign Mucous Membrane; Pemphigoid, Bullous; Respiratory Distress Syndrome; Trachea; Tracheostomy; Treatment Outcome; Young Adult

Topics: Autoantibodies; Dexamethasone; Glucocorticoids; Humans; Immunosuppressive Agents; Laminin; Male; Middle Aged; Mycophenolic Acid; Pemphigoid, Bullous; Remission Induction

Topics: Aged; Autoantibodies; Humans; Immunosuppressive Agents; Laminin; Male; Mycophenolic Acid; Pemphigoid, Bullous; Treatment Outcome

Bullous pemphigoid (BP) is a common autoimmune blistering disease in the adult population, but extremely rare in the pediatric population. Childhood BP usually has a favorable prognosis and responds well to topical and oral steroids. However, for patients that do not respond to corticosteroids, therapeutic alternatives are scarce. We report a case of a toddler with recalcitrant BP who was successfully treated with mycophenolate mofetil (MMF).

Topics: Anti-Bacterial Agents; Clindamycin; Dapsone; Diagnosis, Differential; Drug Resistance; Humans; Immunosuppressive Agents; Infant; Lymphocyte Subsets; Male; Mycophenolic Acid; Pemphigoid, Bullous; Prednisone; Pruritus; Remission Induction; Skin Diseases, Vesiculobullous; Staphylococcal Skin Infections; Superinfection; Urticaria

Topics: Aged; Fasciitis, Necrotizing; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Pemphigoid, Bullous; Soft Tissue Infections

Topics: Aged, 80 and over; Autoantibodies; Autoantigens; Drug Combinations; Follow-Up Studies; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Immunosuppressive Agents; Laminin; Male; Mycophenolic Acid; Pemphigoid, Bullous

Topics: Adult; Anti-Inflammatory Agents; Antibodies, Monoclonal, Murine-Derived; Azathioprine; Drug Resistance; Drug Therapy, Combination; Fatal Outcome; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Immunosuppressive Agents; Male; Mycophenolic Acid; Pemphigoid, Bullous; Prednisolone; Rituximab

Anti-p200 pemphigoid is a recently described autoimmune subepidermal bullous dermatosis characterized by its target antigen and the associated anatomoclinical picture. The treatment is not as yet well defined.. A 73-year-old man consulted for a pruritic bullous eruption with buccal involvement. Direct immunofluorescence revealed linear deposits of IgG and C3 at the dermal-epidermal junction. Elisa screening for circulating anti-BP180 and anti-BP230 antibodies was negative. A diagnosis of bullous pemphigoid was suspected. After an unfavourable clinical outcome under clobetasol and then prednisolone and methotrexate, other immunological tests were performed. Indirect immunofluorescence on NaCl-cleaved skin revealed a deposit of IgG4 antibodies on the dermal side. Immunoblotting showed antibodies directed against a 200-kDa antigen on a dermal extract. A diagnosis of anti-p200 pemphigoid was made. The patient was treated with dapsone combined with prednisolone. Seventy-two hours later, treatment was stopped due to hepatic cytolysis related to immunoallergic hepatitis. Treatment with mycophenolate mofetil was then initiated and resulted in complete remission, which persisted at seven months.. The diagnosis of anti-p200 pemphigoid was made on the basis of a set of clinical and immunological factors. Anti-p200 pemphigoid differs from standard bullous pemphigoid in terms of more frequent cephalic, acral and mucous membrane involvement, as well as a greater degree of miliary scarring. There was no eosinophilia. Elisa screening for anti-BP180 and anti-BP230 antibodies was negative. Immunoblotting showed antibodies directed against a 200kDa protein on dermal extract. The treatment is not well defined, even if dapsone appears to be the most effective therapy. To our knowledge, our patient is the first to be successfully treated with mycophenolate mofetil.. Treatment of anti-p200 pemphigoid is difficult. In our case, treatment by mycophenolate mofetil was effective and could offer an alternative to dapsone.

Topics: Aged; Autoantibodies; Autoantigens; Clobetasol; Dapsone; Drug Resistance; Humans; Immunoglobulin G; Immunosuppressive Agents; Laminin; Male; Methotrexate; Mycophenolic Acid; Pemphigoid, Benign Mucous Membrane; Pemphigoid, Bullous; Prednisolone; Remission Induction; Skin

Topics: Cyclosporine; Dermatologic Agents; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Middle Aged; Mycophenolic Acid; Pemphigoid, Bullous; Prednisolone; Treatment Outcome

The value of 230-kDa bullous pemphigoid antibody (BP230) enzyme-linked immunosorbent assay (ELISA) for the diagnosis of bullous pemphigoid (BP) was investigated, but in the immunological follow-up of the disease remains unknown.. Evaluation of BP230 ELISA for diagnosis, follow-up and prediction of relapse in BP.. Monocenter retrospective and prospective study. Patients with typical BP. Detection of autoantibodies by indirect immunofluorescence (IIF), BP180 and BP230 ELISA tests at diagnosis, during the treatment (disease control or failure) and at treatment stop (relapse or not 3 months after).. 74 patients were included. At diagnosis, BP230 ELISA sensitivity was lower than IIF and BP180 ELISA. Combining both ELISA added a weak gain of sensitivity. Both tests paralleled the clinical evolution, especially in case of disease control. At the end of the treatment, BP230 ELISA was not different in patients with or without relapse.. In routine practice, BP230 ELISA does not seem to be a useful additional test in typical BP.

Topics: Aged; Aged, 80 and over; Autoantibodies; Carrier Proteins; Clobetasol; Cytoskeletal Proteins; Dystonin; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Membrane Glycoproteins; Methotrexate; Mycophenolic Acid; Nerve Tissue Proteins; Pemphigoid, Bullous; Sensitivity and Specificity; Treatment Outcome

Elimination of pathogenic autoantibodies by immunoadsorption (IA) has been described as an effective adjuvant treatment in severe bullous autoimmune diseases, especially in pemphigus. There is much less experience in the treatment of bullous pemphigoid (BP). BP was diagnosed in a 62-year-old Caucasian woman presenting a pruritic rash with multiple tense blisters. Standard treatments with topical and oral corticosteroids, steroid-sparing agents including dapsone, azathioprine, mycophenolate mofetil (MMF) and intravenous immunoglobulins were ineffective or had to be discontinued due to adverse events. An immediate clinical response could be achieved by two treatment cycles of adjuvant protein A immunoadsorption (PA-IA) in addition to continued treatment with MMF (2 g/day) and prednisolone (1 mg/kg/day). Tolerance was excellent. Clinical improvement remained stable after discontinuation of IA and went along with sustained reduction of circulating autoantibodies. Our data demonstrate that PA-IA might be a safe and effective adjuvant treatment in severe and recalcitrant BP.

Topics: Adjuvants, Immunologic; Autoantibodies; Autoantigens; Carrier Proteins; Collagen Type XVII; Cytoskeletal Proteins; Dermatologic Agents; Drug Therapy, Combination; Dystonin; Female; Humans; Immunosorbent Techniques; Membrane Glycoproteins; Middle Aged; Mycophenolic Acid; Nerve Tissue Proteins; Non-Fibrillar Collagens; Pemphigoid, Bullous; Prednisolone; Severity of Illness Index; Sorption Detoxification; Staphylococcal Protein A; Treatment Outcome

The efficacy of topical steroids in bullous pemphigoid (BP) was assessed by prospective therapeutic trials. Systemic corticosteroids and immunosuppressant agents are indicated in situations of failure or relapses.. To report our experience in the management of BP outside therapeutic trials focusing on the outcome of the patients at 6 and 12 months, compliance and follow-up difficulties.. Monocenter retrospective study with collection of clinical, therapeutic and follow-up data after 6 and 12 months.. Ninety-six patients, mean age 84 years, 65 females, 54% had neurological impairment. The initial dose of clobetasol propionate was 30 g/day, followed by a progressive decrease. In the first 6 months, 14% were lost to follow-up and 17.7% died; 62% were controlled with topical steroids alone, and 25% had adjunctive systemic treatment. Difficulties of compliance were mentioned in 34.4%, without significant difference between controlled and noncontrolled patients. After 12 months, 23% were lost to follow-up and 27.1% died. The mean duration of the treatment was 11.7 ± 8.4 months. After the stop, 18.9% of patients relapsed within 3 months.. We emphasize the frequent recourse to systemic treatments in the first few months, the difficulties of compliance and of follow-up in our day-to-day experience.

Topics: Aged; Aged, 80 and over; Clobetasol; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Lost to Follow-Up; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Patient Compliance; Pemphigoid, Bullous; Recurrence; Retrospective Studies; Treatment Outcome

Types of subepidermal autoimmune bullous dermatosis (AIBD) are classified by anatomoclinical picture and target antigen. A new entity has recently been identified: anti-p200 pemphigoid.. An 82-year-old man consulted for a profuse pruritic bullous eruption refractory to the standard treatments for bullous pemphigoid (BP). Direct immunofluorescence examination of a skin biopsy revealed linear deposits of IgG and of C3 at the dermal-epidermal junction, but Elisa screening for circulating anti-BP180 and anti-BP230 antibodies was negative. Indirect immunofluorescence (IIF) testing of cleaved skin revealed a deposit of IgG4 antibodies on the dermal side. Immunoblotting was negative for a dermal extract but showed an antibody directed against a 200-kD epidermal antigen. A diagnosis of anti-p200 pemphigoid was eventually made and the patient was successfully treated with dapsone.. The diagnosis of anti-p200 pemphigoid was made in this case in spite of discrepancy between the IIF and immunoblotting results, and despite the fact that the target antigen in this disease is considered as being restricted to dermal sites. Anti-p200 pemphigoid usually begins in the second part of life and differs from standard bullous pemphigoid in terms of more frequent mucous membrane and cephalic involvement, as well as a greater degree of miliary scarring. This disease appears more prominent in males and is associated with psoriasis in around one third of cases. Autoantibodies recognize laminin gamma-1, an extra-desmosomal protein that contributes to dermal-epidermal adhesion.. This recently described disease as probably under-diagnosed in France. It should be considered in atypical presentations of bullous disease. Diagnosis is confirmed by immunoblotting detection of autoantibodies directed against a 200-kD antigen normally present in the extract. Dapsone appears to be the most effective treatment.

Topics: Aged, 80 and over; Antibody Specificity; Autoantibodies; Autoantigens; Clobetasol; Complement C3; Dapsone; Epidermis; Fluorescent Antibody Technique, Indirect; Humans; Immunoglobulin G; Immunosuppressive Agents; Laminin; Male; Mycophenolic Acid; Pemphigoid, Bullous; Prednisone

Topics: Blood Pressure; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Pemphigoid, Bullous; Tacrolimus

A 56-year-old man with lifelong trauma-induced blisters, nail dystrophy and dental enamel hypoplasia presented with a new spontaneous blistering eruption. Clinicopathologically, he had evidence of both an inherited and an acquired blistering disorder: non-Herlitz junctional epidermolysis bullosa (nHJEB) and bullous pemphigoid (BP). HIstological examination of a skin biopsy found reduced (but not absent) collagen XVII in nonlesional skin, in vivo bound anticollagen XVII antibodies in perilesional skin, and prominent eosinophils in perilesional and lesional skin, with subepidermal blistering. Circulating anticollagen XVII antibodies were also present. Treatment with oral corticosteroids and mycophenolate mofetil led to clinical control of the BP but had no effect on the mechanobullous blistering. Our patient is unusual in that his skin retains some labelling for collagen XVII rather than having the complete absence of immunoreactivity expected in patients with generalized nHJEB. Moreover, we were unable to identify any pathogenic mutations in the COL17A1 gene encoding collagen XVII (or in other EB-associated basement membrane genes). It is plausible that the long-term consequences of basement membrane disruption in our patient, perhaps associated with atypical inherited COL17A1 pathology, might result in a conformationally altered and more immunogenic protein with the subsequent development of anticollagen XVII antibodies and BP as a secondary pathology.

Topics: Autoantigens; Blister; Brain Neoplasms; Collagen Type XVII; Dental Enamel Hypoplasia; Eosinophils; Epidermolysis Bullosa, Junctional; Fatal Outcome; Glucocorticoids; Humans; Immunosuppressive Agents; Magnetic Resonance Imaging; Male; Middle Aged; Mycophenolic Acid; Nail Diseases; Non-Fibrillar Collagens; Pemphigoid, Bullous; Prednisolone

Bullous pemphigoid (BP) is a chronic, autoimmune, subepidermal blistering skin disease with varied clinical presentations. Diagnosis is based on the clinical picture, histopathological findings, and direct and indirect immunofluorescence studies. In unclear cases, ELISA or Western blot analysis helps to establish a definite diagnosis by the detection of immunoglobulin G autoantibodies specific for the hemidesmosomal BP antigens BP230 and BP180. We report 3 cases of BP with an as yet not characterized, distinctive ecthyma-gangrenosum-like presentation. Patients were female, above 80 years of age, physically immobile, and skin lesions showed truncal localization and bacterial colonization. Factors contributing to physical immobility were a high body mass index, psychiatric disease, sedative medication and rheumatic disease. The clinical picture resembled ecthyma gangrenosum but lacked systemic infection with Pseudomonas aeruginosa. Lesional bacteriological studies revealed Staphylococcusaureus and/or P. aeruginosa. Diagnosis proved challenging in all cases. Suspicion has to be high, and repeated diagnostic procedures and additional laboratory studies may be necessary to establish a definitive diagnosis of BP. In summary, we propose this combination of truncal ecthyma-gangrenosum-like lesions with bacterial colonization in the context of older age and immobility as a clinically distinct presentation or variant of BP.

Topics: Adrenal Cortex Hormones; Aged, 80 and over; Anti-Bacterial Agents; Autoantibodies; Autoantigens; Chronic Disease; Ciprofloxacin; Collagen Type XVII; Dermatologic Agents; Doxycycline; Ecthyma; Fatal Outcome; Female; Humans; Mycophenolic Acid; Niacinamide; Non-Fibrillar Collagens; Pemphigoid, Bullous; Treatment Outcome

Shewanella putrefaciens is a Gram negative opportunistic pathogen which causes skin and soft tissue infections and bacteriemia in immunocompromized patients. We report a 86-year-old man, who presented with an infectious cellulitis of the leg associated with Shewanella putrefaciens bacteriemia. This patient was treated by mycophenolate mofetil for a bullous pemphigoid resistant to corticotherapy.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Anti-Infective Agents; Bacteremia; Ceftriaxone; Cellulitis; Ciprofloxacin; Dermatologic Agents; Drug Therapy, Combination; Follow-Up Studies; Gram-Negative Bacterial Infections; Humans; Immunocompromised Host; Male; Mycophenolic Acid; Pemphigoid, Bullous; Shewanella putrefaciens; Time Factors; Treatment Outcome

We report a case of localized bullous pemphigoid (BP) in a woman patient with primary lymphoedema tarda. There is only one previous case reported of localized pemphigoid in an area of lymphoedema, this being of the cicatricial variant. Slow circulation in the lymphatic vessels, increased capillary permeability with preferential localization of antibodies in the area, and potential cleavage of the epidermal junction due to increased hydrostatic pressure leading to autoimmunity, have all been advocated as possible pathogenic mechanisms. Nevertheless, we consider that the mechanism by which localized pemphigoid arises on lymphoedema remains elusive, based on a previous case of generalized BP sparing an area of postsurgical lymphoedema.

Topics: Aged; Cellulitis; Dermatologic Agents; Female; Humans; Lymphedema; Mycophenolic Acid; Pemphigoid, Bullous

Topics: Azathioprine; Humans; Immunosuppressive Agents; Mycophenolic Acid; Pemphigoid, Bullous; Randomized Controlled Trials as Topic; Treatment Outcome

Various antibody-mediated autoimmune disorders are treated with intravenous immunoglobulin (IVIg). While the exact action of IVIg is unknown, it likely acts to rapidly and selectively lower the level of pathogenic antibodies. The most effective use of IVIg, an expensive and potentially toxic treatment of autoimmune disorders, remains undetermined. We propose that the addition of immunosuppressive agents to the IVIg regimen may increase the ability of IVIg to lower the level of pathogenic antibodies.. For 16 months, we observed a 78-year-old patient with autoantibody-mediated bullous pemphigoid who was treated with IVIg and an adjuvant therapy on 2 separate occasions as well as IVIg alone on 2 other occasions. We observed the greatest depression of bullous pemphigoid antibodies when IVIg was combined with an immunosuppressive agent.. These results support the hypothesis that agents that suppress antibody synthesis can offset the rebound in the level of individual antibody that follows their depletion and thus can improve the effectiveness of IVIg treatment while reducing the cost and the potential toxic effects of therapy.

Topics: Aged; Autoantibodies; Drug Administration Schedule; Drug Therapy, Combination; Humans; Immunoglobulin G; Immunoglobulins, Intravenous; Immunosuppressive Agents; Mycophenolic Acid; Pemphigoid, Bullous; Prednisone; Treatment Outcome

Topics: Aged; Anti-Inflammatory Agents; Complement C3; Female; Fluorescent Antibody Technique, Direct; Glucocorticoids; Humans; Immunoglobulin G; Immunosuppressive Agents; Mycophenolic Acid; Pemphigoid, Bullous; Prednisolone; Tablets, Enteric-Coated

Bullous pemphigoid, the most frequent bullous autoimmune dermatosis of the adult, typically presents as disseminated tense blisters on normal or erythematous skin. The diagnosis can be confirmed by direct and indirect immunofluorescence, the detection of circulating autoantibodies against the basement membrane proteins collagen XVII/BP180 and BP230, and histopathology. Autoantibody reactivity against collagen XVII can be measured by ELISA and correlates with disease activity. The ELISA therefore provides a useful tool for monitoring disease activity. Treatment of bullous pemphigoid usually consists of topical and / or systemic steroids in combination with immunosuppressive agents. The intensity of skin involvement and the concurrent diseases and medications of the patient must be considered when selecting a certain treatment. Interdisciplinary cooperation between general practitioners, internists and other specialists facilitates the optimal adaptation of the medication and the early discovery of potential side effects.

Topics: Adrenal Cortex Hormones; Adult; Aged; Anti-Inflammatory Agents; Autoantibodies; Azathioprine; Biopsy; Blotting, Western; Child; Clobetasol; Cyclophosphamide; Dapsone; Dermatologic Agents; Diagnosis, Differential; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique, Direct; Fluorescent Antibody Technique, Indirect; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Male; Mycophenolic Acid; Niacinamide; Pemphigoid, Bullous; Pregnancy; Skin; Vitamin B Complex

Topics: Aged; Dermatologic Agents; Female; Fluorescent Antibody Technique, Direct; Fluorescent Antibody Technique, Indirect; Follow-Up Studies; Humans; Mycophenolic Acid; Pemphigoid, Bullous; Skin; Time Factors

Lichen planus pemphigoides (LPP) and pemphigoid nodularis are rare clinical variants of bullous pemphigoid (BP), which are characterized by histological findings of lichen planus (LP) and nodular prurigo, respectively, and the finding of linear deposits of IgG and/or C3 at the basement membrane zone in perilesional skin. In both cases bullae may arise at the site of pre-existing LP-like or nodular prurigo-like eruptions, and clinically uninvolved skin. The disease spectrum of LPP and pemphigoid nodularis differs from that of classical BP phenotype, and their presentations are often indolent. LPP may predominantly affect a younger age group and is responsive to standard treatments used in acquired autoimmune bullous diseases, while pemphigoid nodularis is more common in elderly women and is relatively resistant to therapy. We describe a patient who had LPP for nearly two decades and subsequently developed a nodular eruption with a concurrently detected antibullous pemphigoid antigen 2 (BP180) autoantibody. His overall clinicopathological features were indicative of LPP evolving into another BP variant, pemphigoid nodularis.

Topics: Autoantigens; Azathioprine; Carrier Proteins; Collagen Type XVII; Cytoskeletal Proteins; Dystonin; Enzyme-Linked Immunosorbent Assay; Humans; Immunoglobulin G; Immunoglobulins, Intravenous; Immunosuppressive Agents; Lichen Planus; Male; Middle Aged; Mycophenolic Acid; Nerve Tissue Proteins; Non-Fibrillar Collagens; Pemphigoid, Bullous; Treatment Outcome

We describe a 76-year-old white woman with a 6-month history of intensive pruritus and excoriated papules resembling subacute prurigo. Histopathology showed signs of chronic dermatitis, whereas findings by direct and indirect immunofluorescence microscopy were compatible with bullous pemphigoid (BP). The patient's serum contained IgG autoantibodies that recognized epitopes on both BP180 and BP230 by Western blot analysis of epidermal extracts. In addition, we found strong reactivity with recombinant NC16A, an immunodominant region of BP180 targeted in the majority of BP sera, whereas no antibodies against the keratinocyte-derived soluble BP180 ectodomain (LAD-1) or the recombinant intracellular domain of BP180 were detected. The patient's disease responded well to oral methylprednisolone and mycophenolate mofetil. Disease activity correlated with enzyme-linked immunosorbent assay reactivity of antibodies to BP180 but not with titers of antibodies to the dermoepidermal junction as determined by indirect immunofluorescence on salt-split skin. Our findings suggest that the subacute prurigo form of BP is a true variant of BP.

Topics: Aged; Autoantibodies; Biopsy, Needle; Blotting, Western; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique, Direct; Humans; Immunohistochemistry; Methylprednisolone; Mycophenolic Acid; Pemphigoid, Bullous; Prognosis; Pruritus; Treatment Outcome

We reviewed the records of patients with chronic cicatricial disease of the conjunctiva for differences in prognosis between clinical and histopathological subgroups of the disease and in therapeutic options.. In 30 patients (58 eyes) with an average age of 69 years (52-86) chronic cicatricial disease of the conjunctiva was diagnosed clinically. Only in 22/30 patients conjunctival biopsies could be performed. The correlation of histopathological and immunohistochemical diagnoses with clinical course under systemic immunosuppression was studied.. 15/22 biopsies led to a classification into different subgroups. Under systemic immunosuppression disease ceased to progress for a mean time of 15 months in 13 of 15 patients with positive biopsies and in 9 of 15 without classification. The results after cyclosporine A therapy (4 of 5 patients stabilized after a mean of 27.5 months) and mycophenolate mofetil (8 of 11 patients stabilized at a mean of 7.8 months) were better than those after therapy with dapsone, azathioprine and cyclophosphamide.. Histopathological and immunohistochemical examinations led to a classification in two-thirds of the patients with clinical aspects of chronic cicatricial disease of the conjunctiva. There was no correlation between different histopathological subgroups, success of therapy and prognosis of the disease. There is little hope in using new systemic immunosuppression such as cyclosporine A and mycophenolate mofetil.

Topics: Aged; Aged, 80 and over; Chronic Disease; Conjunctival Diseases; Cyclosporine; Diagnosis, Differential; Female; Humans; Immunoglobulin A; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Pemphigoid, Bullous; Prognosis

Bullous Pemphigoid (BP) is an autoimmune subepidermal blistering disease appearing predominantly in the elderly. The disease is primarily treated with systemic corticosteroids. However, the treatment can be associated with significant morbidity. Adjuvant corticosteroid sparing therapy can also be associated with significant morbidity. In this study a case of BP which was difficult to control with systemic steroids was successfully treated with mycophenolate mofetil as adjuvant therapy. Mycophenolate mofetil used previously in transplantation, has recently been shown to be useful in autoimmune blistering disorders. Further study to confirm this significant finding and to determine if the long term prognosis of BP can be altered by the drug, is required.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Dermatologic Agents; Female; Humans; Immunosuppressive Agents; Middle Aged; Mycophenolic Acid; Pemphigoid, Bullous; Prednisolone

Mycophenolate mofetil (MMF) has been widely used as an immunosuppressant in organ transplantation. MMF has recently been added to therapeutic regimens for skin disorders. Expanding the use of MMF in dermatology, we describe additional patients with autoimmune and inflammatory skin diseases, including 4 cases of pemphigus vulgaris, 1 case of pemphigus foliaceus, 1 case of perineal and metastatic cutaneous Crohn's disease, 1 case of bullous pemphigoid and psoriasis, and 1 case of psoriasis. Most of these patients had refractory disease or had developed significant side effects to conventional therapy, including azathioprine, methotrexate, prednisone, cyclosporine, acitretin, PUVA, UVB, and tacrolimus. MMF was effective and well tolerated in all these patients. The dosages of MMF ranged from 500 mg twice daily (for psoriasis and Crohn's disease) to 1250mg twice daily (for 3 of 4 patients with pemphigus vulgaris). MMF is an effective and relatively safe immunosuppressant in autoimmune and inflammatory skin diseases.

Topics: Adult; Aged; Autoimmune Diseases; Crohn Disease; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Pemphigoid, Bullous; Pemphigus; Psoriasis; Skin Diseases

Topics: Aged; Female; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Pemphigoid, Bullous; Pemphigus

Topics: Aged; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Mycophenolic Acid; Pemphigoid, Bullous; Prednisone

Topics: Aged; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Pemphigoid, Bullous; Treatment Outcome