Pemphigus in Children

Six boys with pemphigus vulgaris and one boy with pemphigus foliaceus are reported. The youngest patient had onset of the disease at the age of 7 years. Three patients with pemphigus vulgaris were treated with intravenous dexamethasone pulses, while the remaining four received oral corticosteroid therapy. The prognosis in all patients was excellent.     

A comparison of oral methylprednisolone plus azathioprine or mycophenolate mofetil for the treatment of pemphigus

OBJECTIVE: To investigate the safety and efficacy of oral methylprednisolone combined with azathioprine sodium or mycophenolate mofetil for the treatment of pemphigus. DESIGN: A prospective, multicenter, randomized, nonblinded clinical trial to compare 2 parallel groups of patients with pemphigus (pemphigus vulgaris and pemphigus foliaceus) treated with oral methylprednisolone plus azathioprine or oral methylprednisolone plus mycophenolate mofetil. Settings Thirteen departments of dermatology in Germany. Patients We included patients with pemphigus vulgaris (n = 33) or pemphigus foliaceus (n = 7) evidenced by clinical lesions suggestive of pemphigus, intraepidermal blistering on histological analysis of skin biopsy specimens, intercellular deposition of IgG within the epidermis, and immunoblot analysis findings for antidesmoglein 3 and/or antidesmoglein 1 autoantibodies. MAIN OUTCOME MEASURES: The cumulative total methylprednisolone doses and rate of remission. Secondary outcome measures were safety profiles and duration of remission. RESULTS: In 13 (72%) of 18 patients with pemphigus receiving oral methylprednisolone and azathioprine, complete remission was achieved after a mean +/- SD of 74 +/- 127 days compared with 20 (95%) of 21 patients receiving oral methylprednisolone and mycophenolate mofetil in whom complete remission occurred after a mean +/- SD of 91 +/- 113 days. The total median cumulative methylprednisolone dose used was 8916 mg (SD, +/-29 844 mg) in the azathioprine group compared with 9334 mg (SD, +/-13 280 mg) in the mycophenolate group. In 6 (33%) of 18 patients treated with azathioprine, grade 3 or 4 adverse effects were documented in contrast to 4 (19%) of 21 patients who received mycophenolate mofetil. Conclusion Mycophenolate mofetil and azathioprine demonstrate similar efficacy, corticosteroid-sparing effects, and safety profiles as adjuvants during treatment of pemphigus vulgaris and pemphigus foliaceus.     

New approaches to the treatment of pemphigus

In pemphigus vulgaris, treatment with systemic glucocorticosteroids is life saving; it may, however, cause severe side effects, including death. A patient with pemphigus vulgaris and myasthenia gravis was treated for approximately five years with the cholinomimetic Mestinon (pyridostigmine bromide), Imuran (azathioprine), and a topical corticosteroid gel before the need to introduce systemic glucocorticosteroids. Because activation of keratinocyte acetylcholine receptors also has been shown to abolish pemphigus IgG-induced acantholysis in cultured keratinocyte monolayers, a clinical trial of Mestinon was initiated in patients with active pemphigus vulgaris, pemphigus foliaceus, and paraneoplastic autoimmune multiorgan syndrome (also known as paraneoplastic pemphigus). First results indicate that nonsteroidal treatment of pemphigus is possible. Mestinon may be used to slow down progression of the disease and to treat mild cases with chronic lesions on limited areas. Stimulation of the keratinocyte- acetylcholine axis may lead to a therapeutic effect through any of the following mechanisms: (1) stimulating keratinocyte cell-to-cell attachment; (2) accelerating reepithelialization; and (3) competing with the disease-causing pemphigus antibodies, preventing them from attachment to keratinocytes. Glucocorticosteroids and various types of steroid-sparing drugs used to treat pemphigus exhibit cholinergic side effects, including effects on expression and function of keratinocyte adhesion molecules, that are very similar to those produced by the cholinomimetic drugs. Further elucidation of the mechanisms underlying therapeutic efficacy of antiacantholytics may shed light on the immunopharmacological mechanisms of pemphigus antibody-induced acantholysis.     

Treatment of Pemphigus

Ninety-eight cases of various types of pemphigus were treated between 1978-1987. Sixty-one cases were pemphigus vulgaris (PV), 22 cases were pemphigus foliaceus, generalized type (PFG) in which one case developed pemphigus vegetans, 11 cases were pemphigus foliaceus localized type (PFL), and four cases were pemphigus erythematosus (PE). Fifteen mild cases of PV and three mild PFG were treated with corticosteroid (prednisolone or prednisone) alone, and dapsone or cyclophosphamide (CP) were added as treatment failed in two cases of each. Dapsone alone was used effectively in three cases of mild PV. Eight cases of moderate and three cases of severe PV, as well as five cases of moderate PFG, failed to respond to corticosteroid alone but were cleared by the addition of CP. Thirty-two moderate cases of PV and PFG treated with a combination of corticosteroid 60 mg/day plus initial CP and 14 severe cases of PV and PFG treated with corticosteroid 120 mg/day plus initial CP, resulted in clearing skin lesions in 2 months. Azathioprine or chlorambucil were substituted in three cases who developed CP toxicity. Addition of gold sodiumthiomalate in six refractory cases when the above regimens failed, caused a complete remission in two and partial control in four. Higher dosage of prednisolone or prednisone more than 120 mg/day has never been used. Eleven cases of PFL and four cases of PE were treated with uneventfully good results. Intercellular antibody titers became negative within 4.67 months except in refractory cases, however, the treatment was continued for at least 3 years. Herpes simplex superimposed infection was more common than herpes zoster infection.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ultrastructure of uninvolved oral mucosa in pemphigus patients

The uninvolved oral mucosa of seven pemphigus patients was compared with that of age- and sex-matched controls. Three patients had pemphigus erythematodes, two had pemphigus vulgaris, one had pemphigus foliaceus, and one pemphigus vegetans. Five out of seven pemphigus patients demonstrated wider intercellular spaces than the controls. This difference was seen in both basal and spinous epithelial cell layers and was more pronounced in the basal cell layer. There were fewer desmosomes and microvilli than in the controls. It appears that ultrastructural changes in pemphigus also occur in the uninvolved oral mucosa of pemphigus patients.     

Adjuvant high-dose intravenous gammaglobulin in the treatment of pemphigus and bullous pemphigoid: experience in six patients

At present, initial high-dose prednisone is the treatment of choice for patients with pemphigus and bullous pemphigoid. To reduce the risks associated with long-term corticosteroid treatment, other immunosuppressants are often given as steroid-sparing agents. Occasionally, the dose of steroids cannot be reduced. In this study, we report six patients with pemphigus vulgaris, pemphigus foliaceus and bullous pemphigoid, in whom the daily corticosteroid dose could only be tapered to acceptable, effective, maintenance levels following treatment with high-dose intravenous gammaglobulin.     

Pemphigus

Pemphigus is a group of organ-specific autoimmune mucocutaneous disorders with an established immunologic basis. The presence of intraepithelial blisters and erosions of the skin and variable involvement of the mucous membranes characterize its three major variants, pemphigus vulgaris, pemphigus foliaceus, and paraneoplastic pemphigus. Prior to the use of corticosteroids in the 1950s, the natural history of pemphigus vulgaris was relentless progression, with a 50% mortality at 2 years, and almost 100% at 5 years. Today, with mortality rates less than 5%, the focus has changed towards reducing corticosteroid side effects and maintaining optimal quality of life under treatment. This can be achieved by the appropriate use of steroid-sparing agents. This article addresses the comprehensive management of patients with pemphigus.     

A clinico-pathological study of 70 cases of pemphigus

A clinicopalhological study of 70 cases of pemphigus observed over a span of four and a half years from January 1992 to June 1996 at the Sir J.J. Group of Hospitals and Grant Medical College, Mumbai is reported. Pemphigus vulgaris constituted the single largest group of 43 cases, followed by pemphigus foliaceus (25 cases) and pemphigus vegetans (2 cases). Majority of the cases were seen in the age group of 21-60 years, with a slight male predominance. The youngest patient was 14 years while the eldest was aged 75 years. Mucosal involvement was seen in 31 cases of pemphigus vulgaris, as opposed to only 5 cases of pemphigus foliaceus. Flaccid bullae were present in 100% cases. Pruritus was complained of in 14 cases, though it was more common in pemphigus vegetans and vulgaris. Salient histopathological features of pemphigus vulgaris observed were (I) intraepidermal suprabasal blisters (35 cases), (2) presence of acantholytic cells (40 cases), (3) "Row of tombstone appearance" (I8 cases) and (4) acantholysis involving follicular sheath (20 cases). Main histopathological features of pemphigus foliaceus were (1) subcorneal blister (15 case), (2) acantholysis (24 cases) and (3) bulla cavity containing inflammatory infiltrate (12 cases). Both cases of pemphigus vegetans showed hyperkeratosis, papillomatosis and irregular acanthosis with intra-epidermal eosinophilic abscesses besides suprabasal lacunae.     

Drug-induced pemphigus: autoantibodies directed against the pemphigus antigen complexes are present in penicillamine and captopril-induced pemphigus

Pemphigus is an autoimmune blistering disease characterized by circulating autoantibodies directed against the keratinocyte cell surface. The two variants, pemphigus foliaceus and pemphigus vulgaris, can be distinguished at the molecular level by immunochemical studies. The large majority of patients with pemphigus develop the disease spontaneously; however, there is a small group of patients who develop pemphigus after treatment with certain medications, of which penicillamine and captopril are the best documented. Most patients with drug-induced pemphigus have circulating and/or tissue bound epidermal cell surface autoantibodies; however, the molecular specificity of these autoantibodies has not been studied. We performed immunoprecipitation studies utilizing extracts of 125I-labeled suction blister epidermis and the sera of three patients with drug-induced pemphigus foliaceus (two due to penicillamine and one due to captopril) and one patient with captopril-induced pemphigus vulgaris. We found that the three patients with drug-induced pemphigus foliaceus had circulating autoantibodies that are directed against the pemphigus foliaceus antigen complex and that the one patient with drug-induced pemphigus vulgaris had circulating autoantibodies that are directed against the pemphigus vulgaris antigen complex. This study demonstrates that autoantibodies from drug-induced pemphigus patients have the same antigenic specificity, on a molecular level, as do autoantibodies from other pemphigus patients.     

Successful treatment of pemphigus vegetans by addition of etretinate to systemic steroids

Pemphigus vegetans is a rare variant of pemphigus vulgaris and is characterized by flaccid bullae, which become eroded and form vegetations or papillomatous proliferations, especially in the intertriginous areas. ¹ Oral administration of corticosteroids alone does not always induce disease remission in pemphigus vegetans. We report a 44-year-old Japanese man with pemphigus vegetans. Although corticosteroid therapy resulted in healing of the oral ulcers and skin bullae, verrucous vegetations continued to develop. In contrast, by combining corticosteroid with etretinate, verrucous vegetations improved. Thus we propose that the combination therapy of steroid and etretinate might be an effective adjunct in the therapy of pemphigus vegetans.     

免疫抑制剂联合糖皮质激素治疗寻常型天疱疮疗效观察

目的:探讨环磷酰胺联合糖皮质激素治疗寻常型天疱疮的近、远期疗效。方法:收集近4年42例在我科住院经临床、病理确诊为寻常型天疱疮患者的详细资料,比较评估糖皮质激素联合硫唑嘌呤(AZP组)和糖皮质激素联合环磷酰胺(CTX组)治疗后的近、远期疗效。结果:近期疗效,AZP组痊愈率80.0%(16/20),未愈20.0%(4/20);CTX组痊愈率86.4%(19/22),未愈14.6%(3/22),两组相近,差异无统计学意义(P>0.05)。远期疗效,AZP组痊愈40.0%(8/20),控制35.0%(7/20),未控制25.0%(5/20);CTX组痊愈率81.8%(18/22),控制9.0%(2/22),未控制9.0%(2/22),两组差异有统计学意义(P<0.05)。结论:环磷酰胺静脉冲击(五日疗法)联合糖皮质激素疗法是治疗寻常型天疱疮的较好方法。     

Pemphigus in domestic animals

Pemphigus has been recognized in humans for many years. The occurrence of pemphigus in domestic animals is a much more recent observation. In the dog, pemphigus vulgaris was first reported in 1975,^1,2 pemphigus vegetans in 1977,³ pemphigus foliaceus in 1977,⁴ and pemphigus erythematosus in 1980.⁵ In the cat, pemphigus vulgaris, pemphigus foliaceus, and pemphigus erythematosus were reported in 1980.^5,6 Equine pemphigus foliaceus was reported in 1981.⁷ The purpose of this article is to review pemphigus in domestic animals, compare the diseases with their human counterparts, and alert the physician to an exciting area for comparative dermatologic research.     

Pemphigus vulgaris. Combined treatment with intravenous corticosteroid pulse therapy, plasmapheresis, and azathioprine

A 13-year-old child is described who presented with generalized pemphigus vulgaris associated with extraordinarily high titers of circulating autoantibodies against the pemphigus antigen. Because of the lack of response to treatment with reasonably high doses of oral corticosteroids, as well as the very high titer of circulating autoantibodies observed, this patient was treated with intravenous corticosteroid pulse therapy followed by plasmapheresis and then by combination immunosuppressive therapy (prednisone and azathioprine). A rapid clinical response was induced, correlating with reduction and subsequent elimination of the circulating pemphigus autoantibodies. Using such combination therapy, a remission of 12 months was achieved, and prednisone therapy was completely, albeit temporarily, tapered and then discontinued. Subsequent disease flare was then easily controlled with a short course of low-dose oral corticosteroid therapy.     

氮芥制剂治疗白癜风135例临床观察

氮芥制剂治疗白癜风１３５例临床观察赵建林①甘苏①白癜风是皮肤科的常见病，发病率呈上升趋势。近年来，我们应用盐酸氮芥制剂治疗白癜风，现将资料较完整的１３５例统计报告如下。１资料和方法１．１一般资料：１３５例白癜风患者均来自我科门诊。男７８例，女５７例；...     

Management of the immunobullous disorders. II. Pemphigus

In the second of our reviews on the management of the immunobullous disorders, we review the therapy of pemphigus disorders, including pemphigus vulgaris, pemphigus vegetans, pemphigus foliaceus, pemphigus erythematosus, pemphigus herpetiformis, drug-induced pemphigus, IgA pemphigus and paraneoplastic pemphigus.     

Five Japanese cases of antidesmoglein 1 antibody-positive and antidesmoglein 3 antibody-negative pemphigus with oral lesions

Background Oral mucosal lesions develop in pemphigus vulgaris, but not in pemphigus foliaceus. This clinical phenomenon is explained by the ‘desmoglein (Dsg) compensation theory’. Dsg3 and Dsg1 are major autoantigens for pemphigus vulgaris and pemphigus foliaceus, respectively. Dsg3 is overexpressed and Dsg1 is weakly expressed on the oral mucosa. Thus, on the oral mucosa, suppression of Dsg3 function by anti‐Dsg3 autoantibodies is not compensated by weakly expressed Dsg1 in pemphigus vulgaris, while suppression of Dsg1 function by anti‐Dsg1 autoantibodies is perfectly compensated by richly expressed Dsg3 in pemphigus foliaceus. Objectives We present five Japanese patients with pemphigus who deviate from this theory, i.e. all patients showed oral lesions (three also had cutaneous lesions) and reacted only with Dsg1, but not with Dsg3, by enzyme‐linked immunosorbent assay. Methods To confirm whether the unique clinical phenotypes in our patients were due to a different immunological profile from that in classical pemphigus, we examined the reactivity of the patient sera by immunoprecipitation‐immunoblotting analysis using five Dsg1/Dsg2 domain‐swapped molecules. Results The sera of two patients who had only oral lesions tended to react with the extracellular (EC) 5 domain of Dsg1, the domain that is considered nonpathogenic in classical pemphigus foliaceus. Sera of three patients with mucocutaneous lesions reacted with EC1 domain or with both EC1 and EC2 domains of Dsg1, like classical pemphigus foliaceus. Conclusions These results indicate that antigenic diversity of anti‐Dsg1 antibodies in these patients may cause the unique oral mucosal and cutaneous lesions, although further studies are required to elucidate the pathomechanisms.     

Pmphigus in Mali: a study of 30 cases

Summary Pemphigus has been largely studied in developed countries (North America and Europe) and in Brazil. In these geographical settings, pemphigus presents two very different epidemiological and clinical patterns. Little is known about pemphigus in other regions of the world, particularly in Africa. We report here a study of 30 cases of pemphigus observed in Bamako, Mali. Our data suggest that pemphigus in this area presents a distinctive pattern. Our cases of pemphigus were diagnosed on the basis of clinical, histological and direct immunofluorescence studies. We estimated the annual incidence in the Bamako region to be 0.29 cases per 100,000 inhabitants. There was no endemic focus in Mali. The disease was observed mainly in women (24 of 30; 80%), especially those older than 40 years (mean age, 46.7 years), and in the Fulani ethnic group (10 of 30; 33%). Our study group was composed of 25 cases of pemphigus foliaceus (PF) (83%), four cases of pemphigus vulgaris and one case of pemphigus vegetans. Pustules with hypopyon were observed in 11 patients (37%). A diffuse verrucous change in the skin was noted in four cases of erythrodermic PF. In 16 patients with PF, localized verrucous lesions mimicking seborrhoeic keratoses were observed when oral corticosteroid treatment was decreased. Histopathological examination demonstrated eosinophilic spongiosis in 50% of patients.
These data suggest that pemphigus in Mali differs from the two main known patterns of the disease; the North American/European one, and the Brazilian pattern, with which it shares the predominance of superficial forms but otherwise differs in many features.     

Dexamethasone-Cyclophosphamide Pulse Therapy in Pemphigus

Fifty patients with pemphigus (45 pemphigus vulgaris, 5 pemphigus foliaceus) were treated with dexamethasone-cyclophosphamide pulse therapy. The pulse consisted of 136 mg dexamethasone dissolved in 5% dextrose given in a drip over a period of 1-2 hours on 3 consecutive days. In addition, 500 mg cyclophosphamide was added in the drip on the first day. Such pulses were given at monthly intervals. In between the pulses patients were given 50 mg cyclophosphamide orally each day. The results were encouraging, the chief advantage being freedom from side effects of corticosteroid therapy. The lesions healed in 3-4 days and the patients were able to resume their work within one week. Further scope of such therapy in pemphigus is discussed.     

Treatment of cicatricial pemphigoid with mycophenolate mofetil as a steroid-sparing agent.

BACKGROUND: Cicatricial pemphigoid (CP) is a rare autoimmune bullous disease that affects the skin and mucous membranes. It commonly ends by serious complications such as blindness, stenosis, and stricture formation and is difficult to treat. Mycophenolate mofetil has been reported to be effective in the treatment of pemphigus vulgaris, pemphigus foliaceus, and bullous pemphigoid either as monotherapy or as a steroid-sparing agent. OBJECTIVE: Our purpose was to evaluate the effectiveness of mycophenolate mofetil as a steroid-sparing agent in treating patients with CP. METHODS: Three patients with CP were treated with mycophenolate mofetil and prednisolone. RESULTS: All 3 patients responded very well to the therapy. None of them showed relapse of the disease for a follow-up period of 6 to 14 months after complete cessation of mycophenolate mofetil and prednisolone. No side effects were seen. CONCLUSION: Mycophenolate mofetil appears to be a safe and effective steroid-sparing agent in the treatment of CP.