Differential Diagnosis, investigations, and treatment
Differential diagnosis included hyper-IgE syndrome, common variable immunodeficiency, hyper IgM syndrome, and other primary immunodeficiency diseases. Workup demonstrated hypereosinophilia of 3.9 K/mm3 (0-0.6 K/mm3) and elevated IgE 1521 IU/mL (3-423 IU/mL) with normal levels of IgG, A, and M. Her antibody responses to pneumococcal, diphtheria and tetanus antigens were adequate. Lymphocyte subsets showed slightly low absolute CD3 and CD4 count, with normal absolute B cells and NK cells. Mitogen proliferation assays to Phytohemagglutinin, Concanavalin A, and Pokeweed antigens were normal, suggestive of adequate T-cell function.
A next generation sequencing NGS gene panel for inherited immune dysfunction syndromes showed a variant of unknown significance in key immune regulator of PGM3 , including a heterozygous missense mutation c.337C>G (p.Pro113Ala) on exon 4. Other genes that can lead to HIES-related diseases were negative: TYK2, DOCK8, STAT3, IL6, IL6ST, IL6R, ZNF341, TGFBR1, TGFBR2, SPINK5, CARD11 .
She later developed recurrent wheezing responsive to asthma treatment at 4 months old and multiple blinking spells concerned of seizures at 10 months old. Between ages of 1-2, she had two bacterial pneumonia, one required hospitalization. The recurrent eczema flares were unresponsive to initial treatment of topical 0.1% triamcinolone and 2.5% hydrocortisone, antihistamine, emollient, bleach baths, and wet wraps. She also received topical mupirocin for impetiginization. At the fourth months mark since first hospitalization, betamethasone 0.05% ointment and 1mg/kg of prednisolone daily were initiated, which only resulted partial response. At the end of six-month period, dupilumab was initiated with a loading dose of 120mg (12mg/kg) and maintenance dose of 60mg (6mg/kg) every four weeks.