Hypogammaglobulinemia is a common finding in Chronic Lymphocytic Leukemia (CLL). Their etiology is multifactorial, due to disease-related immune defects and chemo-immunotherapy treatment as Rituximab. It is present in up to 85 % of patients at some point in their disease course. It is therefore important to monitor patients for the development of an antibody deficiency due to being susceptible to infections. Strategies to prevent infections in patients with secondary antibody deficiencies include replacement Immunoglobulin (Ig). However, nearly 6% develop skin reaction Ig associated, a rare adverse event reported only in case reports.

A 64 years-old man was diagnosed with CLL in 2011. Despite treatment with Chlorambucil, in July 2013, the patient had therapeutic failure, so he switched to a 2nd-line regimen, with intravenous chemotherapy with cyclophosphamide, vincristine and prednisone for 2 cycles. In September 2013, due to disease progression, he was switched to a 3rd-line regimen with fludarabine and cyclophosphamide. In 2014, he presented an increase in the size of the cervical lymph nodes, so he used 8 cycles of Rituximab. After Rituximab-therapy, hypogammaglobulinemia was detected due to recurrent infections. Then, the patient received Ig monthly with pre-medication. Fifteen days after this Ig infusion, he developed an extensive pruritic, eczematous rash and lichenified skin lesions on the upper limbs. In the following months, 48 hours after the Ig infusion, he presented excoriated eczematous plaques located in the inguinal region and posterior thighs, with follicular pustules (delayed hypersensitivity reaction, type IV). Histological analysis of a skin biopsy specimen revealed subacute spongiotic dermatitis with intraepidermal microvesiculation. The lesions progressively regressed after stopping Ig infusions, oral prednisone, dapsone and topical application of tacrolimus and corticosteroids.

Although the Rituximab used in the treatment of patients with CLL is capable of depleting the population of malignant lymphocytes, they lack specificity and further contribute to the significant immune dysfunction that predisposes these patients to a serious risk of infection. As such, the use of Ig therapy is increasing in the treatment of CLL. However, the severity of its rare adverse effects is often poorly recognized. Dermatologic adverse effects of Ig are rare and include urticaria, papules, eczema, pompholyx, lichenoid dermatitis, and desquamation. The underlying mechanism resulting in skin reactions following treatment with Ig is not clear. Most of these reactions develop within 2 weeks after immunoglobulin administration. The rash is managed with topical/systemic steroids and antihistamine treatment. These adverse events can also lead to cessation of therapy.

This case report highlights the fact that cutaneous adverse effects of IgIV are more common than previously believed. Although the precise mechanism of this cutaneous eruption remains to be elucidated, its occurrence within days of Ig infusion, its characteristic distribution at onset, and its clinical course should be recognized by hematologists and dermatologists.