Dapsone-Induced DRESS Syndrome: A Case Report

Introduction

Dapsone (4', 4’-diaminodiphenylsulphone) is the parent compound for sulfone medications, used in the management of various immunological, hypersensitivity, and skin-related disorders. Additionally, it possesses both anti-inflammatory and antibacterial properties. The predominant adverse effects associated with this medication encompass cutaneous hypersensitivity reactions that are not related to dosage (idiosyncratic), as well as dosage-dependent complications like hemolytic anemia and methemoglobinemia.¹ However, the use of dapsone is associated with distinct side effects, including agranulocytosis, peripheral neuropathy, dapsone hypersensitivity or DRESS syndrome, primary hepatocellular cholestatic hepatitis, permanent retinal damage, as well as hemolytic anemia.² DRESS syndrome is a severe adverse reaction to drugs, typically identified by the presence of a rash, fever, lymphadenopathy, and the potential involvement of one or multiple organs.³ The most commonly involved organ is the liver, leading to acute hepatitis-like conditions. Here, we describe a case of dapsone-induced DRESS syndrome which was managed successfully using oral steroids and antihistamines.

Case Report

This case report describes a 17-year-old female patient admitted to a tertiary care hospital in Bengaluru with complaints of fever along with swelling of the ears and lower jaw associated with pain for 20 days. She received treatment at a local hospital, which included some injections, tablets, and IV fluids (Cefixime/Ofloxacin). However, the medications were not promptly taken and the fever was reported to be intermittent. She gave a history of applying Ayurveda neem leaves on the skin all over the body for 10 days. She also gave a history of skin lesions over the leg and abdomen (? psoriasis) five months back for which she consulted a dermatologist. She was diagnosed with Lichen planus and was prescribed Dapsone/Metrogyl. She was also administered injections for skin lesions along with steroids by a local doctor five months ago. Dapsone was stopped one month before the DRESS episode. Local examination revealed generalized dry peeling of the skin, erythema over the face, a few red spots on the lips, and a few scaly erythematous plaques all over the body (Figure 1).

With the above-mentioned complaints, the patient was admitted to the ward. She was diagnosed with DRESS syndrome secondary to Dapsone. Her liver enzymes were found to be elevated i.e., SGOT-52 U/L, ALP-158 U.L. Also, her absolute eosinophil count was found to be 2.8x10³ /cu mm, ESR was 87 mm after 1 hr. Her Antinuclear antibody ANA (ANA) screening was found to be positive. Her skin biopsy result showed Psoriasiform dermatitis. With the features of psoriasis, she was advised admission to the hospital. During the admission, she was prescribed Atarax and Wysolone. The patient was simultaneously treated with local ointments. The condition of the patient symptomatically improved and she was discharged after a week during which she was advised to consult a dermatologist on an OPD basis with required lab investigations. This case emphasizes the fatal and life-threatening adverse reactions of Dapsone.

Adverse drug reaction Assessment

The casualty assessment of the adverse drug reaction of the patient was done by using the Naranjo Scale and it was found to be ‘probable’ suggesting a strong likelihood that the adverse reaction was caused by the drug. Severity assessment was done using Hartwig’s scale and was found to be Level 4, indicating a ‘moderate severity’ of the adverse reaction. Preventability criteria were assessed by using the Schumock and Thronton Scale which was found to be not preventable implying that it was challenging or impossible to prevent this particular reaction (Table 2).

Discussion

The term "DRESS syndrome" was initially coined by Bocquet et al. to describe a potentially life-threatening condition characterized by a skin reaction that occurs in response to drug exposure (Dapsone in our case report).⁴ 4, 4’-diaminodiphenylsulfone (Dapsone) is extensively used for the treatment of various infectious, autoimmune, and hypersensitivity disorders. Its applications encompass a wide spectrum of conditions, including Hansen's disease (leprosy), inflammatory disorders, and insect bites.³ The pathophysiology of DRESS syndrome is complicated and not yet fully understood. Current evidence suggests that this syndrome develops in individuals who have a genetic predisposition when they are exposed to specific triggering medications. Among the most common triggers are anticonvulsant drugs like carbamazepine, followed by sulphonamides. However, the exact mechanisms underlying the development of DRESS syndrome in genetically susceptible individuals remain a subject of ongoing research.² Besides the drug hypersensitivity, reactivation of HHVs (Human Herpes Virus) and subsequent anti-viral immune responses may potentially contribute to a more severe and prolonged course of DRESS.⁴ Variations in dapsone metabolism, influencing the generation and detoxification of its reactive metabolites, could potentially account for the differing susceptibility of individuals to adverse effects associated with dapsone. The individual differences in dapsone metabolism through N-hydroxylation to hydroxylamines by the hepatic microsomal cytochrome P-450 system have been linked to hematological toxicity (such as methemoglobinemia, hemolytic anemia, and agranulocytosis). However, its involvement in determining the risk of Dapsone hypersensitivity syndrome remains unclear.¹

Discontinuing the causative drug is a critical measure in managing DRESS syndrome. Systemic corticosteroids, particularly prednisolone or an equivalent at a starting dose of 0.5-1.0 mg/kg/day, are the primary treatment for DRESS syndrome. A gradual tapering over a period of 2-3 months is recommended. This extended tapering duration aims to minimize the risk of disease flare-ups and mitigate the potential development of autoimmune long-term sequelae.⁴ Mortality as high as 12-23% has been reported in severe DHS (Drug Hypersensitivity Syndrome).² As a result, each case requires specific adjustments based on the severity of the disease and underlying co-morbidities.

Conclusion

DRESS syndrome is a condition characterized by widespread skin rash along with involvement of internal organs, lymphadenopathy, eosinophilia, and atypical lymphocytosis. Healthcare providers should exercise caution while prescribing medications that have the potential to trigger DRESS syndrome and be vigilant about recognizing its clinical manifestations. Early diagnosis of DRESS syndrome is crucial, and if it is suspected, the suspected drug should be discontinued at the earliest. It has been reported that the earlier the offending drug is withdrawn, the better the prognosis tends to be. The primary treatment for DRESS syndrome typically involves discontinuing the suspected medication and initiating systemic steroid therapy. The administration of steroids should be managed carefully, and a tapering schedule is often followed to gradually reduce the dosage. Early diagnosis, immediate withdrawal of the triggering drug, and appropriate medical management, including systemic steroids, are essential steps in managing DRESS syndrome effectively and improving the patient's outcome.

Conflict of Interest

Nil