El-Sayed ZA¹, Hossny EM¹, Reda SM¹, El-Owaidy RH¹, Aly N¹, Yahia RM^2
1Pediatric Allergy and Immunology unit, Children's Hospital, Ain Shams University, Cairo, Egypt
²Mohammed A Hamid Teaching Hospital for Paediatrics, Khartoum, Sudan.

Background: Chronic granulomatous disease (CGD) is a genetically heterogeneous disorder characterized by recurrent life-threatening bacterial and fungal infections and granuloma formation. Selective IgA deficiency (SIgAD) is one of the most common types of primary immunodeficiency, characterized by low serum levels of IgA (<5 mg/dL) in the presence of normal IgG and IgM. Coexistence of CGD and SIgAD is an interesting issue that is very rarely reported. Immunodeficiency and autoimmune phenomena may occur concomitantly in the same individual. The incidence of autoimmune disease in SIgAD varies between 7% and 36%, especially affecting the lungs and hematological parameters. Due to the persistent infections, patients with CGD could have high levels of immunoglobulins with several autoantibodies. More than 15% of the children with CGD suffer from autoimmune diseases

We report here a 13 year old boy, first order of birth of consanguineous parents whose condition started with recurrent attacks of chest infections and wheezes since the age of two weeks with recurrent hospital admissions and need for parental antibiotics therapy. The condition was associated with multiple skin abscesses. Patient was under built with weight and height below 5^th centiles, with 3^rd degree clubbing, pigeon shaped chest, moderate respiratory distress, pustular skin lesions mainly over extremities some of which were ulcerating (fig.1). Complete blood count showed neutrophilia (ANC: 20.9 x 10³/uL) with thrombocytopenia (83 x 10³/uL). He had also raised inflammatory markers (ESR: 115mm 1st hr; CRP: 48 mg/dl). Autoantibodies, namely, ANA, ASMA, and ANCA were positive. Serum immunoglobulin profile comprised very low IgA (3mg/dl). Immunophenotyping (CD19, CD4, CD8, and CD11b) was normal. The DHR test repeatedly showed marked reduction of oxidative response after stimulation with PMA (6%) with probable X-linked pattern. CT chest showed evidence of emphysematous changes and interstitial lung disease. Lung biopsy revealed congested edematous lung tissue with focal interstitial fibrosis and focal alveolar pneumonitis. Skin biopsy showed neutrophilic panniculitis and leukocytoclastic vasculitis. In addition to antibacterial and antifungal therapy, the patient was maintained on oral prednisone and methotrexate, but then was switched later to cyclophosphamide added to pulsed methyl prednisolone therapy due to rapidly progressive lung disease. There was no family history of similar condition of recurrent infections or autoimmune manifestations

This case presents an example of the rare association between IgA deficiency and CGD that is associated with autoimmune pulmonary and cutaneous manifestations. Molecular studies are underway to identify the underlying genetic defect.

Figure 1: Skin lesions over the right leg with ulcerations and crust formation

Further readings:

• Gerba WM, Miller DR, Pahwa S, Cunningham-Rundles C, Gupta S. Chronic granulomatous disease and selective IgA deficiency. Am J Pediatr Hematol Oncol1982;4(2):155-60.
• Shamsian BS, Mansouri D, Pourpak Z, Rezaei N, Chavoshzadeh Z, Jadali F, Gharib A, Alavi S, Eghbali A, Arzanian MT. Autosomal recessive chronic granulomatous disease, IgA deficiency and refractory autoimmune thrombocytopenia responding to Anti-CD20 monoclonal antibody. Iran J Allergy Asthma Immunol2008;7(3):181-4.
• Yel L. Selective IgA deficiency. J Clin Immunol2010;30(1):10-6.
• De Ravin SS, Naumann N, Cowen EW, Friend J, Hilligoss D, Marquesen M, Balow JE, Barron KS, Turner ML, Gallin JI, Malech HL. Chronic granulomatous disease as a risk factor for autoimmune disease. J Allergy Clin Immunol2008;122(6):1097-103.