Commentary
Drug Rash With Eosinophilia and Systemic Symptoms (DRESS Syndrome) [letter]
Drug rash with eosinophilia and systemic symptoms (DRESS syndrome), also known as drug-induced hypersensitivity syndrome, is a severe condition...
Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome refers to a severe, acute, potentially fatal, multisystem adverse drug reaction characterized by skin rash, fever, hematological abnormalities, and lymphadenopathy with involvement of several internal organs. The pathogenesis of DRESS syndrome is still unknown. Immunological factors such as a defect in detoxification of culprit drugs and infections seem to be involved. The most commonly associated drugs are anticonvulsants and sulfonamides, but dapsone, allopurinol, and minocycline also have been reported to be associated with DRESS syndrome.1
Although therapies for postmenopausal osteoporosis are considered to be safe from cutaneous side effects, there have been several reported cases of DRESS syndrome associated with strontium ranelate.2 Strontium ranelate is not used in the United States; nevertheless, some US patients may be taking this drug as an alternative to the current US Food and Drug Administration–approved drugs for osteoporosis. We report a case of DRESS syndrome in a woman who developed an extensive maculopapular rash, eosinophilia, dyspnea, bilateral cervical lymphadenopathy, and reactivation of Epstein-Barr virus (EBV) with liver damage 3 weeks after administration of strontium ranelate for postmenopausal osteoporosis. Approximately 6 months after total remission of skin conditions, the patient developed autoimmune hepatitis.
Case Report
A 64-year-old woman presented to the emergency department with dyspnea, fever (temperature, 38.5°C), and a generalized rash that had developed a few days prior. The patient reported that she was previously in good health and had no prior allergic episodes. She had been taking strontium ranelate for 3 weeks to treat postmenopausal osteoporosis and reported no other medication use. The patient was hospitalized because of worsening symptoms. Physical examination revealed a pruritic maculopapular rash involving the trunk, arms, and legs (Figure 1) with facial edema, mild inspiratory as well as expiratory dyspnea, and wheezing on all lung fields. An enlarged soft liver (6–7 cm from the right costal arch) and cervical bilateral lymphadenopathy were found.
Figure 1. Physical examination revealed a confluent maculopapular rash extending over the trunk (A and B).
A chest radiograph detected a slight increase of the peribronchial thickening with interstitial involvement at the bilateral basal and perihilar levels, and an ultrasound of the chest confirmed the presence of many enlarged cervical bilateral lymph nodes between 2 and 4 cm in diameter.
Laboratory tests revealed the following values: leukocytosis (21,390/μL [reference range, 4500–11,000/μL]) with eosinophilia (27% [reference range, 2.7%]; 5780/μL [reference range, 0–450/μL]), elevated C-reactive protein (20 mg/L [reference range, 0.08–3.1 mg/L]), elevated erythrocyte sedimentation rate (35 mm/h [reference range, 0–20 mm/h]), a reactivation of EBV confirmed by simultaneous seropositivity to early antigen IgM and EBV nuclear antigen, liver damage with notable increases in liver function tests (aspartate aminotransferase, 51 U/L [reference range, 10–30 U/L]); alanine aminotransferase, 104 U/L [reference range 10–40 U/L]); γ-glutamyltransferase, 52 U/L [reference range, 2–30 U/L]), and no thyroid dysfunction.
Blood and urine cultures; antinuclear antibodies; and serology for hepatitis A, B, and C virus, as well as herpes simplex virus type 6 (HHV-6), chlamydia, Mycoplasma, and cytomegalovirus (CMV) were all negative. Histologic examination after skin biopsy showed keratinocytes with spongiosis, intraepidermal eosinophilic infiltration, suffusion of red blood cells with perivascular granulocytes, and lymphocyte inflammatory infiltrate (Figure 2).
Figure 2. Histology revealed keratinocytes with spongiosis, intraepidermal eosinophilic infiltration (A)(H&E, original magnification ×40), suffusion of red blood cells with perivascular granulocytes, and lymphocyte inflammatory infiltrate (B)(H&E, original magnification ×100).
A diagnosis of DRESS syndrome was made on the basis of the following clinical data supported by laboratory findings: generalized maculopapular rash, eosinophilia, lung involvement with dyspnea, bilateral cervical lymphadenopathy, and liver damage, as well as an identified reactivation of EBV and onset of symptoms 3 weeks after treatment with strontium ranelate.
The patient was given intravenous methylprednisolone 120 mg once daily for 1 week in gradually decreasing doses. Three weeks of steroid therapy were necessary to obtain the first good results. Improvement of the patient’s clinical condition was considerably slow. Fever and rash gradually disappeared and the patient was discharged with oral corticosteroids. In the 2 months after starting systemic corticosteroid therapy, the lesions had not progressed and all other clinical symptoms improved. A slow but notable regression of the skin reaction was observed.
In a subsequent checkup approximately 8 months following initial presentation, the patient developed autoimmune hepatitis. There was a notable increase in liver enzymes and serum immunoglobulin content as well as positivity of antinuclear antibodies (1:160) and antimitochondrial antibodies (1:160). A liver biopsy was performed and confirmed the histologic pattern of autoimmune hepatitis. Thyroid function was reevaluated, but no other autoimmune disease was identified.