Case Presentation: A 36-year-old male with history of keratoconus, corneal scars following corneal transplant, asthma, eczema, chronic herpes simplex virus 1 (HSV-1) and varicella zoster virus (VZV), presented with concerns of eye involvement secondary to HSV-1 versus VZV reactivation. Physical examination revealed periorbital edema, vesicular lesions in trigeminal nerve ophthalmic distribution, neck and upper extremities. Slit-lamp examination showed fluorescein uptake in the periphery of bilateral eyes and multiple corneal lesions. Laboratory workup, including HIV-status was unrevealing except for neutrophilic leukocytosis of 11.92, COVID-19 status, and hypergammaglobulinemia E of 21,686 IU/mL. Given history of recurrent herpes zoster ophthalmicus (HZO) and 3 weeks of worsening periocular rash, ophthalmic erythromycin ointment and IV acyclovir were initiated along with plating corneal cultures negative for VZV or HSV-1 but positive for oxacillin-resistant Staphylococcus aureus.Detailed patient history was obtained, which revealed recurrent childhood infections necessitating hospitalization and intravenous antibiotics. This raised concern for atypical presentation of autosomal dominant hyper-IgE syndrome (AD-HIES). He was discharged with gabapentin, TMP-SMX, acyclovir, and ophthalmic erythromycin. He was referred to an immunologist for further testing.Genetic testing, including STAT1 gain-of-function and CARD11 mutation was scheduled. In addition, immunological testing including NK cell lymphocyte subsets, T-cell mitogen proliferation, and anti-CD3 was ordered for follow-up outpatient evaluation.
Discussion: AD-HIES or Job’s syndrome, is a primary immunodeficiency characterized by eczematoid dermatitis, recurrent sinopulmonary infections, skin abscesses, and marked elevation in serum IgE (2000-100,000 IU/mL).1 Recurrent sinopulmonary infections, primarily driven by S. aureus2, present as “cold abscesses” without erythema and warmth and can result in deep organ abscesses, mucocutaneous candidiasis, and aspergillosis.3 Patients with AD-HIES can present with chronic pruritus with widespread eczematous dermatitis involving the eyelids. Viral infections, including HSV-1 and VZV, and ophthalmologic findings are rare in AD-HIES but have been documented in autosomal-recessive HIES.4 In AD-HIES, STAT1/CARD11 gain-of-function and STAT3 loss-of-function mutations are most common.5 STAT1 and STAT3 are responsible for activating cytokines and growth factors including Th17. Impaired production in AD-HIES leads to increased susceptibility to infections.6,8 CARD11 activates protein complexes such as nuclear factor-kappa B and MTOR complex 1, which are necessary for cellular signaling in T and B cells.7 Treatment centers around wound healing and prophylactic anti-staphylococcal/antimycotic agents.
Conclusions: This case illustrates the link between recurrent HZO reactivation and AD-HIES. Recurrent infections point to immunodeficiencies or malignancies. In the setting of recurrent viral infections, VZV and HSV reactivation is common. When coupled with staphylococcal skin infections, reactivation is rare. In the undiagnosed patient, it should prompt workup for immunodeficiencies, particularly AD-HIES. Diagnosis involves presence of hypergammaglobulinemia E and cardinal features, including recurrent pneumonia. Consideration of ophthalmic, skin, and viral superinfections is critical to managing and treating underlying etiology.