Rashid, Sheikh Abdur

Abstract Introduction: Idiopathic CD4 lymphocytopenia is a disorder with CD4 counts below 200 cells/mm3 or less than 20% of total lymphocytes without an acquired or genetic cause. Case Summary: A 41-year-old female with history of Celiac disease complicated by hyposplenism developed fevers, weight loss, sicca symptoms, widespread erythematous rash, sinusitis, multifocal pneumonia refractory to antibiotics and pulmonary embolism. Workup demonstrated isolated weakly positive PR3 antibody of 1.2 (reference range < 1.0), CD4 count of 78 with negative ANA, ENA, HIV, CMV, EBV, HTLV, fungal, mycobacterial testing and mildly low IgM. PET-CT noted FDG avidity in the paranasal sinuses, lung opacities and salivary glands. Sinus biopsy showed chronic inflammation and fibrosis. Sputum cultures were positive for MSSA and Pseudomonas. Lung biopsy noted fibrinous organizing pneumonia. Skin biopsy demonstrated pauci-inflammatory vacuolar interface dermatitis with discontinuous weak granular deposition of C3 on basement membrane. A small-intestinal biopsy noted villous blunting and polymorphous T cell infiltration of the lamina propria. Bone marrow biopsy redemonstrated polytypic T cells with inverted CD4:CD8 ratio, but neither harbored an abnormal T cell population. Treatment for presumptive GPA was undertaken with corticosteroids, Rituximab, and Avacopan with transient improvement. CRP was elevated at 65.1 mg/dL (reference range < 5.0mg/dL). However, CD4 count had increased to 260 (reference range 365-1437) with 20% CD4 cells, low B cells, normal CD8 and NK cells, and IgG4 levels elevated at 180 mg/dL (reference range 2.4-121.0). LDH was elevated at 455 U/L (reference range 122-222) but flow cytometry, SPEP, and FLC ratio were unremarkable. Rhinoscopy demonstrated purulence, nasal septal perforation, and crusting of the larynx and subglottis. Salivary gland biopsy noted chronic sialadenitis without malignancy. Repeat CD4 count was 93. Given recurrent, refractory pulmonary infections, IVIG was considered, but prior to administration the patient developed worsening hypoxemia and pressor requirements and was transitioned to comfort cares. Discussion: It is crucial to rule out conditions causing lymphopenia, such as severe sarcoidosis, Sjogren's, IgG4-related disease, cutaneous T cell lymphoma, and splenectomy. While common complications include opportunistic infections, invasive cancers and autoimmunity, their absence may be explained by normal CD3 and CD8 counts. Despite complications, mortality is generally not increased, although baseline CD4 counts of less than 150 cells/mm3 may predict death. Decreases in CD4 counts in the setting of rising immunoglobulin levels may represent antibody production against lymphocytes. While evidence on the use of IVIG is limited, it may be beneficial when hypogammaglobulinemia or life-threatening infections are present.