Behandeling van Huidaandoeningen bij Syndroom van Dress

DRESS Syndrome: Renal Involvement in Two Cases – A Comprehensive Analysis and Literature Review of Improved Diagnosis and Treatment

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare hypersensitivity reaction involving the skin and various visceral organs, the kidneys are the second most affected organ. Many drugs are reported to be associated with DRESS, particularly antiepileptic agents and allopurinol. Certain human leukocyte antigen (HLA) haplotypes, in combination with a particular drug, can further contribute to an increased risk of DRESS. Symptoms often develop 2 to 8 weeks after drug initiation. If diagnosis is delayed, DRESS can be a life-threatening condition.

Case Reports:

We present cases of 2 patients. The first patient was an 86-year-old Polish woman who developed acute kidney injury and skin lesions with accompanying leucocytosis and eosinophilia during long-term antibiotic therapy with piperacillin/tazobactam and ciprofloxacin. The second patient was a 37-year-old Asian woman with predialysis chronic renal disease stage V in the course of IgA nephropathy. Two weeks after starting allopurinol in a standard dose, she presented with maculopapular rash, facial edema, fever, liver injury, and eosinophilia. Renal function started to deteriorate, but she did not require dialysis.

In both cases, the discontinuation of the above-mentioned drugs and the introduction of steroid therapy and intravenous immunoglobulins allowed for clinical improvement and recovery. In the second case, the extended 4-locus HLA typing was performed retrospectively, and allele HLA-B*5801 was found.

Conclusions:

Due to the rare occurrence and heterogeneous manifestation of DRESS, its diagnosis can pose many difficulties. In-depth analysis of symptoms, medicines taken, and laboratory findings enable the implementation of appropriate treatment and recovery.

Key words: Allopurinol, Drug Hypersensitivity Syndrome, Piperacillin, Tazobactam Drug Combination, Renal Insufficiency, Chronic

DISCUSSION

Although there are a variety of etiologies, such as infections and underlying malignancies, drugs remain the predominant cause of SJS. The most commonly implicated drugs are anticonvulsants, sulfa derivatives, NSAIDs, penicillins, cephalosporins and allopurinols. 1 , 9 The characteristic skin lesions seen in SJS are diffuse erythematous macules with purpuric, necrotic centers, and overlying blistering. These cutaneous lesions often demonstrate a positive Nikolsky sign, which is further detachment of the epidermis with slight lateral pressure. Painful erosions of the mucous membranes are common and may affect the lips, oral cavity, conjunctiva, nasal cavity, urethra, vagina, gastrointestinal tract and respiratory tract during the course of the illness. The mucosal membranes most often affected in our study were the oral cavity and eyes. SJS is fatal in 5-15% of cases. 3 , 8 Both the incidence of the condition and the associated mortality appear to be increased in immunocompromised patients.

DRESS and SJS are part of a spectrum of adverse cutaneous drug reactions. However, the pathophysiology of DRESS and SJS has not been elucidated fully. Various theories have been proposed, including both immunological and non-immunological mechanisms. 3 , 13 The current pathophysiological explanation for DRESS is immunological. Drugs with reactive metabolites can modify cellular proteins and target an autoimmune response against the skin or liver cells. 11 It now appears that the immunological mechanisms associated with SJS are initiated by the Fas antigen, a cell surface molecule that can mediate apoptosis. 3

Corticosteroids remain the agents most widely used for treating DRESS, although the doses used vary widely across case reports. 8 Favorable results have been reported with their use. In the absence of a well-established therapy, primary and secondary prevention have key roles in the management of these two syndromes. 1 , 8 Milder cases of SJS can be managed in an inpatient setting using the same fundamental therapeutic protocol used for the treatment of burns. The use of medications to treat SJS remains controversial. Treatment with corticosteroids, while effective in most other acute inflammatory disorders, is controversial.

Background

Below we present 2 case reports on DRESS. In the first case, DRESS was induced by the extremely rare culprit drugs piperacillin/tazobactam (Pip/Taz) and ciprofloxacin. In the second case, a patient with end-stage renal failure experienced DRESS and uneventfully underwent renal transplantation a year later.

Case 1

Diffuse erythemathous skin lesions with discreet scaling covered most surfaces of the body, especially the face, neck, and chest.

There are erosions on the lips and oral mucosa. Vesicles on the lips and tongue are shown.

Case 2

A 37-year-old Vietnamese woman was admitted to our hospital because of an acute maculopapular rash involving more than 50% of her body surface, which had appeared 1 week earlier. Other symptoms included sore throat, headache, and fever. Two weeks before admission to the hospital, she had started allopurinol in a dose of 100 mg once daily due to asymptomatic hyperuricemia. Upon a dermatological consultation, allopurinol was discontinued, and the patient was prescribed prednisone at a dose of 15 mg p.o. once daily and a steroid ointment, but no improvement was observed. The medical history of the patient was significant for end-stage renal disease due to chronic glomerulonephritis/IgA nephropathy. She had been awaiting preemptive renal transplantation. The patient had no previous history of autoimmune diseases. Her home medications included sodium bicarbonate, bisoprolol, nitrendipine, and calcium bicarbonate. Upon admission, the patient presented with skin involvement, including the disseminated erythematous and erythematous-papular lesions located in particular on the trunk and limbs, as well as the presence of erosions on the lips and conjunctival redness ( Figure 3 ). Other physical examination findings were insignificant. The laboratory test results revealed a neutrophil count of 8710/µL (82% of all WBC), without signs of leukocytosis or eosinophilia, and increased levels of SCr, at 6.4 mg/dL, and urea, at 161 mg/dL (1 year prior to the episode described, those parameters were 1.5 mg/dL and 49 mg/dL, respectively). There were also laboratory signs of liver damage, with alanine transaminase activity (ALT) level of 396 IU/L, aspartate transaminase level (AST) of 216 IU/L, and gamma-glutamyltransferase level of 76 IU/L. Among inflammation markers, procalcitonin was elevated, at 2.71 ng/mL, and CRP was 8.1 mg/L. Ultrasound of the abdomen and radiography of the chest were insignificant.