Diffuse exanthematous drug eruption associated with intravenous immunoglobulin

Abstract

Diffuse exanthematous drug eruption due to intravenous immunoglobulin (IVIg) is a rare adverse event reported only in case reports. We present a case of a 71-year-old woman with a diffuse maculopapular rash 5 days after receiving an IVIg infusion for treatment of chronic inflammatory demyelinating polyneuropathy. She was managed conservatively with antihistamines; she was already receiving prednisone 25 mg daily as part of treatment for the neuropathy. The rash resolved over 2 weeks.

Intravenous immunoglobulin (IVIg) is a pooled plasma product used for neurologic disorders including chronic inflammatory demyelinating polyneuropathy (CIDP).^1,2 It has been associated with dermatologic side effects like pruritus and focal skin eruption. However, extensive exanthematous skin eruptions with IVIg are exceedingly rare.¹

CASE DESCRIPTION

A 71-year-old woman presented to the emergency department with a generalized rash for 2 days. She mentioned that the rash was nonpruritic; it started on her back and upper extremities and progressed to involve her face, trunk, and lower extremities. Her past medical history was significant for CIDP diagnosed 30 years earlier, hyperthyroidism, and monoclonal gammopathy of unknown significance. She was initially on high-dose prednisone with some benefit, but she continued to have symptoms. Over the course of time, she had been on a combination of prednisone, IVIg, and azathioprine with good symptom control. She was on Gamunex-C at 1 g/kg per dose divided over 2 days every 4 weeks and had received her second infusion of Gamunex-C 5 days before presentation. Her home medications included alprazolam 0.5 mg as needed, methimazole 5 mg daily, prednisone 25 mg daily, and simvastatin 20 mg nightly. Her temperature was 103.1°F. She had blanching macular erythema predominantly on her face, back, and extremities (Figure 1). She did not have oral mucosa or conjunctival involvement. Blood cultures, chest x-ray, and urinalysis were negative for infection. Liver function tests, thyroid function tests, and complete blood count were normal. The patient had been on other home medications for years and had tolerated them without any adverse events. We concluded that IVIg was the most likely culprit in the absence of an infection and other medications that could explain the presentation. The patient was managed conservatively with antihistamines. She was given intravenous vancomycin and cefepime in the emergency department, but they were later discontinued. Her rash was thought to be nonpruritic because she was on prednisone for CIDP. The rash cleared over the next few days. After discharge, the patient was placed on Gammaplex, and the rash has not recurred.

Figure 1.

Maculopapular rash on the patient’s (a) face, (b) back, (c) upper extremities, and (d) lower extremities.

DISCUSSION

An exanthematous skin eruption associated with IVIg generally resolves within 1 to 4 weeks from the time of onset. The exact mechanism for this adverse event is unknown. It has been suggested to be due to a hypersensitivity reaction to a constituent in the IVIg formulation.¹ Men are more commonly affected than women. In a cohort of 15 patients, most cases had a generalized erythematous rash and desquamation, mostly of the palms. An adverse event was noted after the first dose in only 20%,² which makes us suspect that this might be an idiosyncratic reaction. The rash is managed with topical/systemic steroids and antihistamine treatment.³ These adverse events can also lead to cessation of therapy despite the above treatment and changing of the IVIg product.²