Eczematous Dermatitis in the Setting of Hyper-IgE Syndrome Successfully Treated With Omalizumab

Hyper-IgE syndrome (HIES) is a rare primary immunodeficiency (<1 case per million population) characterized by elevated serum IgE levels, recurring staphylococcal skin abscesses, and pneumonias.¹ Patients with HIES may show peripheral eosinophilia, eosinophilic infiltration of the skin, and increased susceptibility to infection.² In newborns, it first manifests as an eruption³ that usually persists as a moderate to severe eczematoid dermatitis into childhood and adulthood. This multisystem disorder is associated with skeletal, facial, and dental abnormalities.¹ We report the first case to our knowledge of a patient with HIES with severe recalcitrant eczematous dermatitis successfully treated with high-dose monoclonal anti-IgE therapy.

A 26-year-old woman with multiple autoimmune phenomena was referred for evaluation. She had severe unremitting eczematous dermatitis poorly controlled by tacrolimus and systemic steroids. Despite treatment, she experienced significant pain and pruritus that limited her activities. She reported dermatitis since birth and multiple cutaneous complications. Her medical history included viral meningitis at age 9 years and recurrent infectious bronchitis, pneumonias, and cystitis. She retained several of her primary teeth requiring extraction. She had controlled asthma and allergic rhinitis since childhood.

She was the only child of nonconsanguineous parents. Family history was notable for seasonal allergies in her mother and thyroid cancer and acute leukemia in 2 maternal aunts. In 1999, she had autoimmune hemolytic anemia and was diagnosed as having hepatitis C viral infection. She then developed alopecia universalis and autoimmune hypothyroidism requiring treatment with corticosteroids and levothyroxine, respectively.

Physical examination revealed lichenified skin with extensive erythema and eczematous plaques hypersensitive to light touch, excoriations, and dry scaly plaques along the flexor surfaces of her upper and lower extremities, chest (Figure, A), and back. She exhibited hypertelorism, widened nasal root and alae, scoliosis, and joint hyperextensibility. Results of laboratory investigations revealed a differential eosinophil count of 9.2% (normal, 0%-5%) and IgE concentration of 1083 IU/mL.

Based on her medical history and HIES score⁴ (41 points), a diagnosis of HIES was made. We initiated treatment with omalizumab (recombinant monoclonal anti-IgE antibodies), 450 mg subcutaneously every 2 weeks. This is the maximum dose reported⁵ in the context of immunosuppressant limitations imposed by a history of hepatitis C infection and failure of conventional therapies. One month after initiating omalizumab treatment, her dermatitis and asthma were markedly improved. She attained complete remission after 3 months of treatment, and her eosinophil differential count decreased to 2.4%. She remained well 6 months after stopping treatment (Figure, B).

Omalizumab binds to the FcεRI receptor binding site on the IgE molecule thereby inhibiting its binding to its receptor on mast cells and basophils and their subsequent activation.⁵ Dosing is based on body weight and baseline serum IgE concentration not exceeding 700 IU/mL to administer at least 0.016 mg/kg/IU of IgE per milliliter of serum over a 4-week period.

The dermatitis associated with HIES is attributed to the increased IgE-stimulated mast cell release of histamine. In light of omalizumab's success in treating various atopic diseases associated with elevated IgE levels,⁶ we attempted a trial of omalizumab. Although costly, omalizumab has proven beneficial in a patient with HIES and very limited therapeutic options.

Correspondence: Dr Sánchez-Ramón, Department of Immunology, University General Hospital “Gregorio Marañón,” Calle Doctor Esquerdo, 46, 28007 Madrid, Spain (ssanchez.hgugm@salud.madrid.org).

Financial Disclosure: None reported.