We present 2 cases of dyshidrotic eczema secondary to intravenous immunoglobulin infusion. The first patient was a 58-year-old man who had been diagnosed with Guillain-Barré syndrome after presenting with sock-like paresthesia, unstable gait, and diminished tendon reflexes. The patient was treated with intravenous immunoglobulin, and his symptoms gradually improved. Ten days after admission, he began to develop asymptomatic lesions on his palms and soles.

Physical examination revealed punctate vesicular lesions filled with clear fluid on an erythematous base located bilaterally on the palms and soles (Fig. 1). Some of the vesicular lesions were purpuric in appearance and filled with blood, especially in dependent parts of the body (Fig. 2). No mucosal involvement or lesions at other sites were observed.

Figure 1.

Vesicular lesions on an erythematous base on the palm of the first patient.

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Figure 2.

Vesicular blood-filled lesions on the sole of the first patient.

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Histopathology revealed an epidermis with psoriasiform hyperplasia, lymphocytic and erythrocytic exocytosis, and extensive spongiosis with formation of large subcorneal vesicles. The underlying dermis showed a moderate superficial perivascular lymphohistiocytic inflammatory infiltrate accompanied by blood extravasation.

The second patient was a 67-year-old man whose personal history included removal of pleomorphous sarcoma on the right pectoral muscle and treatment with radiotherapy and chemotherapy. He was admitted 8 months after surgery for assessment of ataxia. During admission, and given the gradual worsening of his condition, he received intravenous immunoglobulin, and his symptoms partially resolved. A dermatological evaluation was ordered for the asymptomatic skin lesions, which were very similar to those of the first patient: vesicular lesions filled with clear fluid on an erythematous base located on the palms and soles. Histopathology findings were very similar to those of the first patient (Fig. 3).

Figure 3.

Vesicular lesions on an erythematous base on the palm of the second patient.

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We diagnosed both patients with dyshidrotic eczema secondary to treatment with intravenous immunoglobulin.

The lesions resolved in both cases with topical corticosteroids, although they reappeared in the first patient during the second cycle of treatment.

Intravenous immunoglobulins are isolated from plasma obtained from between 1000 and 100 000 persons. They are subsequently purified to eliminate or inactivate infectious agents and prevent the formation of aggregates.1 They have been approved by the European Medicines Agency for the following indications: primary immunodeficiency syndromes with impaired antibody production; hypogammaglobulinemia and recurrent bacterial infections in patients with chronic lymphocytic leukemia in which antibiotic prophylaxis has not been successful; hypogammaglobulinemia and recurrent bacterial infection in patients with plateau-phase multiple myeloma who did not respond to pneumococcal vaccination; hypogammaglobulinemia in patients who undergo allogenic stem cell transplantation; congenital AIDS with recurrent bacterial infection; primary immune thrombocytopenia; patients at high risk of bleeding; patients undergoing surgery to correct their platelet count; Guillain-Barré syndrome; and Kawasaki disease.2 They are used off-label in numerous hematologic, neurologic, rheumatologic, infectious, and dermatologic conditions.1

Intravenous immunoglobulin has a good safety profile, and most adverse effects are associated with administration. The adverse effects, which are immediate, mild, and transient, consist of flulike symptoms that include headache, flushing, general malaise, chest tightness, fever, chills, myalgia, fatigue, dyspnea, back pain, nausea and vomiting, diarrhea, changes in blood pressure, and tachycardia. The most severe adverse effects are usually late in onset and manifest as thromboembolic events and renal, neurologic, and/or hematologic toxicity. Cutaneous adverse effects appear in 0.4%-6% of patients in the form of transient urticaria or maculopapular rash, palmar pruritus, hair loss, erythema multiforme, erythematous purpuric rash, petechiae on the limbs, ulceration of the oral mucosa, transient epidermolysis bullosa, lichenoid eruptions, and Baboon syndrome.3

Eczema is rarely associated with administration of intravenous immunoglobulin. In their review of the literature, Gerstenblith et al.4 found 64 patients with eczematous reactions associated with intravenous immunoglobulin. The most common findings were the presence of multiple punctate erythematous vesicles grouped together on the palms and soles. Histopathology revealed the spongiotic loculated vesicles that are typical of dyshidrosis and a perivascular infiltrate composed of lymphocytes and eosinophils, as well as lymphocytic exocytosis in the epidermis. Overall, 62.5% of patients had lesions of dyshidrotic eczema on the palms and soles or on the palms and soles and at least 1 other affected site. Most patients received intravenous immunoglobulin for neurologic diseases. Almost all patients responded well to topical corticosteroids or did not require treatment, although treatment with oral corticosteroids was occasionally necessary. The eczematous reaction improved in all the cases reported, although in 1 case, itching persisted for months after suspending intravenous immunoglobulins. Despite these findings, therapy was suspended because of the eczematous reactions. No clear mechanism has been identified that might explain the association with eczema,4 although some authors suggest a hypersensitivity reaction to the drug or vehicle that has not been demonstrated with patch testing or prick testing.5

In the first patient, we thought that the skin lesions were gloves and socks syndrome, given that the histopathology findings were consistent with this syndrome and that this and Guillain-Barré syndrome can be triggered by common infectious agents such as parvovirus, Mycoplasma, Epstein-Barr virus, and cytomegalovirus6,7; however, the results of serology testing to various pathogens were repeatedly negative.

Other diseases that can be taken into consideration with this type of lesion include palmoplantar pustular psoriasis, allergic contact dermatitis, dyshidrosiform tinea, scabies, id reaction, herpes simplex, and other bullous diseases such as pemphigus, pemphigoid, and epidermolysis bullosa.5

As this was a first episode of asymptomatic lesions associated in time with infusion of intravenous immunoglobulin (8 and 5 days, respectively) and reappearance of the lesions during the second treatment cycle in the first patient, we were able to confirm the diagnosis.