Dapsone

Dapsone and other sulfonamides have been used successfully in the treatment of patients with a variety of blistering skin diseases. The patients most likely to respond to dapsone therapy have a predominantly neutrophilic infiltrate in their skin. Therefore the blistering diseases with the most consistent responses to dapsone therapy include dermatitis herpetiformis and linear IgA disease. Dapsone's precise mechanism of action is unknown. In vitro studies have shown that dapsone can interfere with the production of and response to neutrophil chemoattractants and that it may impair the neutrophils' ability to localize to sites of inflammation and produce toxic oxygen intermediates. The safe use of dapsone requires an understanding of the pharmacology and adverse effects of the drug. Hemolytic anemia and methemoglobinemia are two of the dose-related adverse effects. Agranulocytosis, motor neuropathy, and dapsone hypersensitivity syndrome are some of the severe idiosyncratic effects that can occur in patients treated with dapsone. Dapsone is an effective drug for the management of patients with some blistering disease, especially those with predominant neutrophilic infiltrates in the skin. Careful patient selection and close monitoring of patients during therapy with dapsone are critical elements in the safe and effective use of dapsone for patients with blistering skin diseases.     

In utero development of epidermolysis bullosa acquisita

We report the case of an infant born with perioral vesicles that rapidly spread to involve his mouth and the majority of his body. Histopathology, immunofluorescence, and enzyme‐linked immunohistochemistry assays confirmed a diagnosis of epidermolysis bullosa acquisita (EBA). His mother had no history of EBA, and serum indirect immunofluorescence was negative. The patient improved rapidly with local wound care and oral dapsone.     

Suicide with dapsone

A case of suicide with dapsone is reported in a female medico chemical analysis report confirmed it to be death due to dapsone. Management in case of dapsone poisoning is also discussed.     

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.     

Severe methemoglobinemia due to topical dapsone misuse in a teenage girl

Dapsone gel is a topical treatment for facial acne in adolescents and adults, and while systemic dapsone therapy is known to be associated with methemoglobinemia, once-daily topical dapsone has been well tolerated with few side effects in large randomized controlled trials. We describe the first reported case of severe methemoglobinemia in a healthy adolescent using daily topical dapsone. Although the medication was prescribed for facial use only, the patient reported topical use over her back and chest as well. This case illustrates the potential for significant systemic dapsone absorption even with daily topical dosing and demonstrates the need for clear anticipatory guidance to prevent the potential morbidity and mortality associated with methemoglobinemia from improper topical dapsone use.     

Efficacy of Dapsone in the Treatment of Pemphigus and Pemphigoid

Dapsone is a chemotherapeutic agent primarily used in treating leprosy, Pneumocystis jiroveci(previously carinii) pneumonia, and malaria. It is also used as an adjuvant in the treatment of pemphigus and pemphigoid. To assess the role of dapsone in the treatment of pemphigus and pemphigoid, a retrospective review of reports in the English-language literature was conducted. Information on the number of patients treated, their average age, prior therapies, indications for use, protocol (dose and interval) used, concomitant therapies, reported adverse effects, and clinical outcomes were analyzed. There were 35 case reports/series published describing the use of dapsone in a total of 427 patients. Data on 55 pemphigus patients were obtained from several case reports and some case series and one randomized controlled trial. Of these, 32 patients with pemphigus vulgaris and 14 patients with pemphigus foliaceus responded to dapsone. Data from 13 case series, each including at least five patients, accounted for 372 patients with pemphigoid. The overall response rates to dapsone, when given either alone or in combination with corticosteroids or immunosuppressive agents, were 84% in mucous membrane pemphigoid, and 81% in bullous pemphigoid. Hemolysis was the most common adverse effect observed. Dapsone is a promising and useful agent in patients with autoimmune mucocutaneous blistering diseases, especially in mucous membrane pemphigoid. It can be used as a corticosteroid-sparing agent. Therefore, its combined use with oral corticosteroids may be useful in pemphigus vulgaris and bullous pemphigoid. Adverse effects of dapsone are dose dependent and usually reversible. Hemolysis and concomitant anemia secondary to hemolysis are expected in most patients. In the opinion of the authors, dapsone is underutilized in the treatment of autoimmune mucocutaneous blistering diseases.     

Treament of bechcet's disease

A case of Behcet's disease treated initially wiht corticosteroids to which dapsone was added subsequently and being kept in remission with dapsone alone is presented. High maintenance dose of corticosteroids necessitated the substitution with dapsone.     

De Novo Histoid Leprosy

Histoid leprosy is an uncommon entity with specific clinical, histopathological and bacteriological features. Histoid lepromas are sudden eruption of dome shaped lesions usually associated with dapsone resistance, as a variant of lepromatous leprosy or rarely arising de novo. We report a case who presented for the first time with histoid features with no history of taking dapsone/antileprosy treatment earlier in an elderly male with small to large lesions over normal skin in the post-leprosy elimination era.     

Drug susceptibility of Mycobacterium leprae: a retrospective analysis of mouse footpad inoculation results from 1983 to 1997

We analysed the results of mouse foot pad (MFP) tests performed between 1983 and 1997 in our laboratory for the cases referred with clinical suspicion of relapse/drug resistance. A total of 214 cases, with clinical suspicion of relapse/drug resistance were investigated for susceptibility to the drugs of MDT by MFP inoculation. Among 96 inoculations that showed conclusive results, 81 (84%) were fully sensitive to dapsone, suggesting that most of the clinically suspected relapse is due to drug susceptible Mycobacterium leprae. Of the remaining 15 strains (16%) found resistant to dapsone, 13 (87%) were of high grade resistance and one strain each of intermediate grade and low grade dapsone resistance, suggesting that most of the dapsone resistance is secondary in nature. No case of rifampicin resistance was found. Only one case of combined dapsone and unconfirmed clofazimine resistance was found. No other combined multidrug resistance was observed in our analysis.     

Linear immunoglobulin a bullous disease of childhood responsive to intravenous immunoglobulin monotherapy

We report a case of linear immunoglobulin A bullous disease in a 9-year-old boy who presented with rapidly progressive severe disease and could not tolerate dapsone because of high liver enzymes within a week after a low dose of dapsone in association with an underlying fatty liver. He showed remarkable improvement with intravenous immunoglobulins used as monotherapy, with a rapid clearance and a sustained remission after stopping the treatment.     

Pyoderma gangrenosum treated with sulfasalazine and dapsone

A case of pyoderma gangrenosum treated initially with sulfasalazine and later with dapsone and being kept in remission with dapsone alone is being reported.     

Follicular mucinosis responding to dapsone

A case report is presented of a patient with an eruption of acute onset shown to be follicular mucinosis by biopsy, and which responded to oral dapsone therapy.     

Dapsone in Behçet's disease: a double-blind,placebo-controlled,cross-over study

The study was designed to investigate the effects of dapsone in the treatment of mucocutaneous manifestations of Behçet's disease and the possible prophylactic role of dapsone in a double blind/placebo controlled clinical trial. Twenty patients diagnosed according to the International Study Group criteria as Behçet's disease were included in the study. Patients were randomly allocated to receive either dapsone 100 mg daily or placebo for three months in a double‐blind manner. After three months, patients were crossed over and followed for a further three months. Patients were followed up in each visit by assessing the number, size, duration and frequency of oral and genital ulcers, other cutaneous manifestations, and systemic manifestations of the disease. A pathergy test was done on each visit. Laboratory investigations included hemoglobin concentration, white blood cell count, ESR, and C‐reactive protein. In dapsone‐treated patients, there were significant reductions in the oral and genital ulcer parameters as well as the incidence of other cutanous and systemic manifestations. In the placebo‐treated group, there were no significant changes in these parameters. The pathergy test result as well as those of other laboratory tests were all decreased in the dapsone‐treated group. Although this study was a small scale study, it shows that dapsone was effective in treatment of mucocutaneous manifestations of Behçet's disease and possibly in prophylaxis against systemic manifestations of the disease. This result should lead to a larger scale study with a longer duration of follow‐up.     

Primary dapsone-resistant Hansen's disease in California. Experience with over 100 Mycobacterium leprae isolates

We found that in the years 1978 through 1981 only one of 54 previously untreated patients with Hansen's disease was found to harbor dapsone-resistant Mycobacterium leprae. That single strain was only partially resistant, ie, it was resistant to 0.0001% dapsone in a mouse diet but not to higher concentrations. During the years 1983 through 1988, M leprae from 47 previously untreated patients presenting to clinics in San Francisco, Calif, and Los Angeles, Calif, grew in mice. None of these strains was found to be dapsone resistant. Thus, from 1978 through 1988 only one of 101 M leprae isolates obtained from skin biopsy specimens from patients with leprosy was found to be resistant to dapsone. We have concluded that primary dapsone resistance still does not appear to be a significant problem in California. Owing to the fact that our single resistant case and those reported from international sources are, in general, partially resistant, the potential importance of partial dapsone resistance is discussed.     

Multiple relapses in borderline leprosy--a case report

A case of borderline lepromatous leprosy with a history of 5 years duration of disease, was first seen in 1971 and treated with graded doses of dapsone in the OP Clinic of the Institute. He became inactive and bacteriologically negative in 3 years. While continuing on dapsone therapy he relapsed into active dapsone resistant leprosy 3 1/2 years later. He was admitted in the hospital and given Rifampicin 600 mg. daily for 15 days along with dapsone 100 mg. daily. He again became inactive and bacteriologically negative within 3 years. 3 years later under regular dapsone therapy he relapsed again for the second time into active BT leprosy, but remained bacteriologically negative. He was given 3 drug regimen subsequently and became clinically inactive within 15 months.     

DAPSONE INDUCED PERIPHERAL NEUROPATHY

Summary.— A further case of peripheral neuropathy has occurred in the course of dapsone therapy. It was predominantly motor in type, but a sensory element was present. It recovered completely after dapsone withdrawal. Electromyography and nerve conduction studies showed the neuropathy to be axonal in type.     

Cicatricial pemphigoid: treatment with mycophenolate mofetil

BACKGROUND: The severity of cicatricial pemphigoid (CP) varies. First-intent treatment of mild or moderate cases is dapsone. In life or sight-threatening cases, intravenous cyclophosphamide pulses are efficient but may have digestive side effects and imply repeated hospitalizations. Mycophenolate mofetil (MMF) is an oral and well tolerated immunosuppressant agent which has proved its efficacy in pemphigus and some bullous pemphigoid. In CP, encouraging case reports have been previously published. We report herein a retrospective study about 14 patients who have received MMF since 2000. PATIENTS AND METHODS: There were 5 men and 9 women, with a mean age of 69 years. MMF was introduced in 3 different clinical situations: immediately in relay to cyclophosphamide in 7 patients with severe CP (group I); in case of a mild-severe relapse at distance from with dranal of cyclophosphamide in 3 patients (group II); as first-intent immunosuppressant agent in 4 patients whose disease was not under control with high-dose dapsone, but not life - or sight-threatening (group III). In all these patients, the disease was invalidating and not controlled by dapsone +/- sulfasalazine, but did not threaten life or sight. The aim was to achieve satisfying control of the disease with an oral and well tolerated immunosuppressant agent, and to maintain good quality of life. The dose of MMF was 1.5 or 2 g per day. The criteria of MMF efficacy was the healing of previous lesions and the absence of new progressive lesions. RESULTS: MMF was efficient in obtaining or maintaining a good control of the disease in 10/14 patients, as long as the underlying treatment with dapsone (2 mg/kg/d) was maintained. In 7/10 cases, it was possible to decrease the dapsone dose in order to improve hematological tolerance. In the 3 other cases, a relapse occurred when the dose of dapsone was decreased. MMF was inefficient in controling the disease in 4/14 patients (29 p. 100). Clinical and biological tolerance of MMF was good in 13/14 patients. DISCUSSION: In this series, MMF was proposed to heterogenous patients, who presented at that time a mild-moderate disease and for whom we wanted in improve the quality of life. MMF seems to be an interesting drug, capable of obtaining or maintaining satisfactory control of the disease and permitting the decrease of dapsone doses in some mild-severe CP. However MMF must not replace cyclophosphamide in severe sight or life-threatening forms of CP.     

A near fatal case of the dapsone hypersensitivity syndrome in a patient with urticarial vasculitis

Dapsone (4,4'-diaminodiphenyl sulphone) is used for a variety of dermatological conditions including immunobullous diseases and urticarial vasculitis. Side-effects are common and include lethargy, headaches, methaemoglobinaemia and haemolysis. Severe adverse effects are rare but the dapsone hypersensitivity syndrome is well recognized. Symptoms include fever, haemolytic anaemia, lymphocytosis and hepatitis. We report a near fatal case of the dapsone hypersensitivity syndrome in a patient with urticarial vasculitis. This diagnosis should be remembered in any patient who becomes unwell whilst taking dapsone.     

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.