Dapsone and sulfapyridine

Dapsone and sulfapyridine are structurally related compounds with anti-microbial and anti-inflammatory effects. Dapsone remains the most important drug for leprosy and is useful in the prophylaxis of Pneumocystis pneumonia in patients with HIV disease. The medical treatment of choice for dermatitis herpetiformis is dapsone; and sulfapyridine also can be used for those patients who are intolerant of dapsone. Other neutrophilic disorders also may respond to these drugs. Toxic side effects of both dapsone and sulfapyridine are mediated through the hydroxylamine metabolite. These include hemolysis, methemoglobinemia, and agranulocytosis. Careful monitoring for possible adverse reactions includes frequently performing complete blood counts and regular blood chemistry profile determinations.     

Sulfasalazine and dermatitis herpetiformis

Dermatitis herpetiformis that is unable to be controlled using dapsone and a gluten-free diet presents a therapeutic challenge. Three cases that responded well to sulfasalazine are presented. Two cases, who were unable to tolerate dapsone, had a rapid response to sulfasalazine, without apparent side-effects. The third case with dapsone-responsive blistering dermatoses, presumed to be dermatitis herpetiformis on the basis of serology, showed an excellent clinical response to sulfasalazine, but after 6 weeks of therapy had to cease it because of side-effects. Sulfasalazine is metabolized variably to sulfapyridine, a sulphonamide known to be an effective therapy for dermatitis herpetiformis but no longer available. Sulfasalazine should be considered as a management option for dermatitis herpetiformis.     

Should all patients with dermatitis herpetiformis follow a gluten-free diet?

Aim To assess the effect of a gluten-free diet in Irish patients with dermatitis herpetiformis, and whether treatment with a gluten-free diet is as important for patients with a normal small bowel biopsy us for those with villous atrophy. Background Though a gluten-free diet is recommended in the management of dermatitis herpetiformis, many patients find it intolerably restrictive. To date we have recommended it only to patients with abnormal small bowel histology. Methods Forty patients with dermatitis herpetiformis who attended our clinic between 1979 and 1994 were studied retrospectively. Villous atrophy was present in 20 (64%) of 31 initial small bowel biopsies in patients not on a gluten-free diet. Results The median time to a 50% reduction in dapsone requirements was 6 months in patients who followed a gluten-free diet. (n = 14). 10.5 months in those who had a gluten-reduced diet (n = 4) and 10.5 months in those who took a normal diet (n = 22). Four of 14 patients (29%) on a gluten-free diet were able to discontinue medication in 1–5 years compared with 2 of 22 (9%) on a normal diet. The mean time to a 50% reduction in dapsone requirements was similar in patients with and without villous atrophy. 9.3 versus 9.0 months in patients on a gluten-free diet and 12.0 versus 15.3 months in patients on a normal diet. Conclusion We conclude that a gluten-free diet should be strongly encouraged in all dermatitis herpetiformis patients, since those with normal small bowel biopsy findings benefit equally from the diet as do those with villous atrophy.     

Dapsone-induced peripheral neuropathy. Case report and review

A severe motor and a minor sensory neuropathy developed in a man being treated with dapsone (4,4'-diaminodiphenylsulfone) for dermatitis herpetiformis. He had received dapsone for 16 years before any signs of neurotoxicity became evident. Electrodiagnostic and clinical features were consistent with an axonal neuropathy. Clinical characteristics of dapsone-induced neuropathy include a motor neuropathy affecting the extremities, usual onset within five years after the initiation of dapsone therapy, dapsone dosage usually equal to or greater than 300 mg/day, and, almost always, complete recovery from the neuropathy after dapsone-dose reduction or withdrawal. The patient was found to be a slow acetylator of sulfamethazine, and therefore is a slow acetylator of dapsone. An HLA typing was done on the patient. New cases of dapsone-induced neuropathy should be HLA typed and have acetylation profiles in an attempt to identify future high-risk patients. This case is noteworthy for the length of time of dapsone usage (16 years) and the low daily dosage of dapsone (100 mg) taken prior to the development of neuropathy.     

Dapsone-induced peripheral neuropathy.

Peripheral neuropathy occurred in a 32-year-old man who was receiving dapsone (Aviosulfon) for dermatitis herpetiformis. Neurological examination showed polyneuropathy that involved the median and ulnar nerves, with a lesser involvement of other peripheral nerves. After treatment with dapsone was discontinued, the neuropathy reversed itself, with practically complete return of function of all nerves involved.     

A comparison of IgA positive and IgA negative dapsone responsive dermatoses

A study of thirty-three patients with a clinical diagnosis of dermatitis herpetiformis (DH) referred to our DH clinic over the last 11 years is reported. Twenty-six were referred by other consultant dermatologists. The diagnosis had been made by the clinical features and response of the rash to dapsone. Seventeen patients were found to have IgA in the uninvolved skin (IgA positive) and in sixteen no IgA was found (IgA negative). The duration of the rash prior to referral to the DH clinic was 3 months to 19 years (mean 5.0 years) for the IgA negative patients and 2 months to 22 years (mean 5.2 years) for the IgA positive group. The length of follow-up was 3 months to 11 years (mean 5.0 years) for the IgA negative, and 2–11 years (mean 5.6 years) for the IgA positive group. During follow-up the rash cleared completely and required no treatment in seven of the sixteen IgA negative patients. Thirteen of these sixteen patients no longer required dapsone, but six patients were receiving alternative treatment. In the three patients still taking dapsone IgA has not been found on subsequent biopsy. Of the seventeen IgA positive patients only three were able to stop dapsone during follow-up and in these three the IgA was still detected in the skin. Small intestinal mucosa was abnormal in eight of eleven IgA positive patients, but was normal in all thirteen IgA negative patients in whom jejunal biopsies were performed. An alternative diagnosis to DH has subsequently been made in thirteen of the sixteen IgA negative patients. Although the significance of IgA in the skin in DH is not known it appears to be part of the disease process. Patients who have a rash suggestive of DH and which is dapsone responsive, but in whom IgA is not found in the uninvolved skin, usually turn out to have a dermatosis other than dermatitis herpetiformis. Referral to a unit with expertise in immunofluorescence techniques of skin biopsies would appear to be helpful.     

IgA bullous pemphigoid: a distinct blistering disorder

We report a patient with an eccrine carcinoma who developed localized blistering which clinically resembled pemphigoid, histologically showed subepidermal blistering with features of both dermatitis herpetiformis and bullous pemphigoid, responded to dapsone and exhibited linear IgA deposition on direct immunofluorescence. The nosological position of patients with linear IgA deposition and subepidermal blistering is not clear. A review of the literature reveals that in adults linear IgA deposition may occur in three separate situations: dermatitis herpetiformis, bullous pemphigoid and a third condition of which our case is an example which is best termed IgA bullous pemphigoid. This condition is distinguished from cases of dermatitis herpetiformis with linear IgA by the clinical features and the site of IgA deposition on immunoelectronmicroscopy. It is distinguished from cases of bullous pemphigoid with linear IgA by the absence of circulating IgG antibasement membrane zone antibody, the therapeutic response to dapsone and the frequent occurrence of circulating IgA antibasement membrane zone antibody. IgA bullous pemphigoid has not previously been reported with a carcinoma but the association lends further support to the concept that this eruption represents a variant of pemphigoid.     

Clinical response of dermatitis herpetiformis skin lesions to a gluten-free diet

Patients with dermatitis herpetiformis have been studied prospectively for 2 years to assess the effect of a gluten-free diet (GFD) on control of the skin lesions. Daily requirements for oral medication with sulphapyridine or dapsone were reduced by GFD treatment and if complete clinical remission of the skin disease occurred, it was maintained while the diet was strictly observed. However, complete remission did not occur significantly more often in GFD-treated patients than in patients taking a normal diet. Many of the latter group exhibited variation in their drug dose requirements during the period of study. GFD treatment seems desirable for the majority of patients with dermatitis herpetiformis, not only to correct the intestinal abnormality but also to minimize the dose of drugs necessary to control the skin lesions.     

Long-term remission in patients with dermatitis herpetiformis on a normal diet

BACKGROUND: A life-long gluten-free diet is the treatment of choice for dermatitis herpetiformis, which is considered to be coeliac disease of the skin. OBJECTIVES: To investigate the effects on long-term remission of dermatitis herpetiformis in patients who underwent a gluten challenge and subsequently reintroduced dietary gluten. PATIENTS AND METHODS: We studied 38 patients (14 male and 24 female) with biopsy-confirmed dermatitis herpetiformis. They had followed a gluten-free diet for a mean of 8 years, achieving clinical remission and intestinal normalization. The patients were asked to reintroduce gluten in their diet and agreed to undergo skin and intestinal biopsies during the follow-up. RESULTS: Of the 38 patients abandoning a gluten-free diet, 31 reported the onset of rash within an average of 2 months. Seven subjects (three males, mean age 15 years at challenge) experienced no clinical or histological relapses (median follow-up 12 years), and lost IgA immunoglobulin from the skin. The two series of patients differed in terms of age at diagnosis (mean age: 26.6 vs. 6 years), the use of dapsone (one of 31 vs. four of seven) and adherence to the gluten-free diet (strict compliance in 26 of 31 vs. none of seven). CONCLUSIONS: Our data suggest that the ingestion of small doses of gluten in childhood and/or the use of an anti-inflammatory drug may modify the immunological response inducing immune tolerance. We report long-term clinical and histological remissions in seven patients with dermatitis herpetiformis after the reintroduction of dietary gluten.     

Natural history of dermatitis herpetiformis in southern Sweden

A retrospective clinical survey of 96 patients with dermatitis herpetiformis (DH) was performed in two defined populations of 425,000 in southern Sweden. The incidence of DH was 1.05-1.13/100,000 inhabitants/year and the prevalence was approximately 20-25/100,000 inhabitants. In one-third of DH patients the age at onset was greater than 60 years. In women with DH a strong connection to thyroid dysfunction was observed, but also other conditions of probable autoimmune pathogenesis were found in both sexes. No connection to malignant disease was observed. DH seems to be less active the later in life it starts. Several patients with DH manage without dapsone or need dapsone just occasionally in connection with bouts. This is the case even without a gluten-free diet. Many mild cases of DH were observed without a gluten-free diet; therefore, this restricting regimen should be prescribed only in more active cases of DH.     

疱疹样皮炎的研究进展

【摘要】 疱疹样皮炎是一种与乳糜泻相关的自身免疫性大疱病,多发于携带HLA?DQ2或HLA?DQ8等位基因的高加索人。研究表明,疱疹性皮炎患者血清中存在多种针对转谷氨酰胺酶等抗原的抗体,表皮型转谷氨酰胺酶是其自身抗原。疱疹样皮炎的发病除与遗传和麦胶敏感有关外,还可能与肠道菌群微生态失衡有关。无麦胶饮食和氨苯砜仍然是疱疹样皮炎的主要治疗手段。本文从流行病学、发病机制、临床表现、实验室检查、诊断及治疗等方面对疱疹样皮炎进行总结。     

The protective effect of vitamin E on the hemolysis associated with dapsone treatment in patients with dermatitis herpetiformis.

OBJECTIVE--This study looked at whether oral vitamin C and vitamin E would protect the erythrocyte from oxidant damage caused by dapsone in patients with dermatitis herpetiformis. DESIGN--Fifteen consecutive patients with dermatitis herpetiformis taking dapsone therapy received, in addition, 800 U/d of vitamin E for 4 weeks; then 1000 mg of vitamin C per day for 4 weeks, and, finally, combined vitamin E and vitamin C therapy for 4 weeks. Hemolysis indexes were assessed at baseline and after each 4-week period. RESULTS--Statistical analysis of the results suggests that oral administration of 800 units of vitamin E daily for 4 weeks confers partial protective effect against dapsone-induced hemolysis in patients with dermatitis herpetiformis. CONCLUSION--Partial protection against dapsone-induced hemolysis by orally administered vitamin E, if confirmed as being clinically relevant by further trials, may allow clinicians to continue dapsone therapy orally in patients who develop significant hemolysis. Prophylactic vitamin E to minimize potential hemolysis at the initiation of dapsone therapy may also be appropriate.     

The incidence and prevalence of dermatitis herpetiformis in Utah.

BACKGROUND AND DESIGN--The incidence and prevalence of dermatitis herpetiformis has never been formally evaluated in any area of the United States. Several northern European studies have shown prevalence rates ranging from 1.2 per 100,000 to 39.2 per 100,000. The present study was performed to evaluate the incidence and prevalence of dermatitis herpetiformis in Utah. Information from 240 patients diagnosed with dermatitis herpetiformis was compiled from hospital records throughout Utah, as well as the sole private dermatopathologist in the state, and from the university referral center of the state. Criteria for inclusion in the study were a clinical diagnosis of dermatitis herpetiformis plus granular deposition of IgA in dermal papillae by direct immunofluorescence of uninvolved skin, or histopathologic findings consistent with the disease. Clinical diagnosis and response to dapsone alone was considered insufficient for inclusion in the study. On the basis of these criteria, as well as exclusion of non-Utah residents, 188 of the original 240 patients qualified for the study. RESULTS--The prevalence of dermatitis herpetiformis in Utah in 1987 was 11.2 per 100,000. The mean incidence for the years 1978 through 1987 was 0.98 per 100,000 per year. The mean age at onset of symptoms for male patients was 40.1 years, and that for female patients was 36.2 years. The male-female ratio was 1.44:1. CONCLUSIONS--This represents the first evaluation of the incidence and prevalence of dermatitis herpetiformis in the United States. These results are similar to those of the previous studies, probably because of Utah's largely northern European ancestry. This population base, plus a much smaller than average black and Oriental population, is likely to have produced a higher incidence and prevalence in Utah than would be seen in other areas of the United States.     

Erythema annulare centrifugum revealing linear IgA dermatitis of childhood

Linear IgA dermatitis was diagnosed in a 13-year old girl with erythema annulare centrifugum (EAC) on the basis of the criteria laid down by Jablonska: vesiculo-bullous eruption with specific patterns on subsequent flare-ups, subepidermal vesicles and bullae with papillary eosinophilic abscesses in erythematous areas, positive linear IgA antibody response at direct immunofluorescence in the lamina basal, absence of intolerance to gluten and responsiveness to sulfapyridine and dapsone. This patient was followed up for 10 years. During the first 5 years any attempt at withdrawing dapsone resulted in quick relapse which always remained responsive to that drug. After 5 years discontinuing dapsone was no longer followed by relapse, and the girl was considered clinically cured. Yet direct immunofluorescence in healthy skin remained positive for 2 years after treatment was stopped, as has previously been reported. At the age of 23, after 5 years without treatment the patient remained cured. This case demonstrates that linear IgA dermatitis is one of the causes of EAC. Autoimmune bullous diseases, such as pemphigus with eosinophilic spongiosis, bullous pemphigoid and dermatitis herpetiformis, are known to present as EAC. Direct cutaneous immunofluorescence is necessary to the aetiological diagnosis of EAC.     

ABSORPTION AND EXCRETION OF 35S DAPSONE IN DERMATITIS HERPETIFORMIS

SUMMARY.– The variability of dosage of dapsone required to control dermatitis herpetiformis is well known but unexplained. As a first step in the investigation of this problem this paper describes the results of estimations of serum levels and urinary excretion levels after a single oral dose of 100 mg. ³⁵S dapsone given to patients with and without dermatitis herpetiformis. For comparison the levels were measured by radio-activity and by chemical methods. Radiochromatographic studies were also carried out to determine the form in which dapsone circulates and is excreted. Autoradiographs of biopsies are also discussed.     

Dapsone and severe hypoalbuminaemia in dermatitis herpetiformis

A case of severe hypoalbuminaemia in a patient on long-term dapsone treatment for dermatitis herpetiformis is described. The mechanism for this complication is uncertain, but increased intravascular albumin catabolism has been suggested.     

IMMUNOGLOBULINES IN DERMATITIS HERPETIFORMIS AND VARIOUS OTHER SKIN DISEASES

SUMMARY.— Lowering of the mean IgM-globulin value and elevation of the mean IgA-globulin value were noted in a group of 21 patients with dermatitis herpetiformis. IgM levels determined before and after dapsone therapy revealed no clear evidence of a dapsone effect on this immunoglobulin. No relationship was noted between the IgM-globulin levels and the intestinal mucosa biopsy grading. Fluctuations in the IgM values were noted and in some patients a fall in this immunoglobulin occurred during an exacerbation the disease. Immunoglobulin patterns were studied in 7 other skin diseases. The abnormalities noted in psoriasis closely paralleled those found in dermatitis herpetiformis.     

Dapsone acetylation in dermatitis herpetiformis

The metabolism of dapsone was studied in ten patients with proven dermatitis herpetiformis. Seven of the patients, who were slow acetylators of sulphadimidine, also acetylated dapsone slowly. Three of the patients were rapid acetylators of both drugs. The control of symptoms did not seem to be related to the plasma concentrations of dapsone or of its metabolite monoacetyldapsone. Haemato-logical side effects, however, were related to plasma dapsone concentrations.     

A Case of Pemphigus Herpetiformis Occurring in a 9‐Year‐Old Boy

Abstract: Pemphigus herpetiformis (PH) is a rare autoimmune vesiculobullous disease. It clinically mimics dermatitis herpetiformis and has immunofluorescent findings typical of pemphigus. PH occurs in adults more commonly than children and is often effectively treated with dapsone. We report a case of PH occurring in a 9‐year‐old boy that was refractory to dapsone and to various other steroid‐sparing medications but resolved with methotrexate.     

Neurologic symptoms posing as dapsone-induced polyneuropathy in two patients with dermatitis herpetiformis

The clinical picture of neuropathy caused by dapsone is usually progressive muscle weakness and wasting, most often involving distal muscles of the extremities. Two patients with neurologic symptoms following the use of dapsone for dermatitis herpetiformis are reported. Both patients had normal motor conduction velocities, and negative results on physical examination of muscle wasting. We conclude that their clinical presentation was not due to dapsone-induced neuropathy. A discussion and a review of cases of this unusual effect of dapsone are included.