Sex: M
Vaccine: PPV
Symptoms: Blood immunoglobulin A decreased, Blood immunoglobulin G decreased, Blood immunoglobulin M decreased, Bronchoalveolar lavage, Bronchoscopy
Clinical narrative: failure to respond to pneumococcal vaccination / poor vaccination response to pneumovax 23; poor pneumococcal antibody titers; Literature report: variable immunodeficiency (CVID) with granulomatous interstitial lung disease (GLILD) and SARS COVID-19 infection: case report and review of literature. Allergy, Asthma and Clinical Immunology 2021; 17(1): 98.  This literature marketed report has been received from the authors of a published literature article, titled as stated above, and refers to a 27-year-old male patient who, in June of 2017, started having recurrent episodes of pneumonia and was found to have thrombocytopenia. He complained of recurrent productive cough with green discharge over 1.5 years. His other concurrent conditions included: intermittent headaches, sinus pressure, nasal congestion, rhinorrhea, intermittent diarrhea, fatigue and loss of smell, however he denied any fever, chills or night sweats. At the start of his disease course, the patient had lost around 10-11 pounds. His family history was pertinent for a brother who also had thrombocytopenia and died from a brain aneurysm.  The patient underwent hematologic monitoring of his platelet counts over a 12 month which showed varying levels between 91 and 108 × 10^9/L. The rest of his complete blood count (CBC) with differential, complete metabolic panel and urinalysis were normal. The patient was also found to have hypogammaglobulinemia. Quantitative immunoglobulin panels were completed four times over an additional 12-month period revealing the following: IgG 256-308 mg/dl (700-1600), IgM 9-25 (40-230), IgA 23-33 (70-400). A computed tomography (CT) of chest and abdomen revealed mediastinal and upper abdominal lymphadenopathy, splenomegaly, and multiple pulmonary nodules.  In May 2018, the patient was vaccinated with the first dose of pneumococcal vaccine, polyvalent (23-valent) (PNEUMOVAX23) and in June 2018, he received the second dose of pneumococcal vaccine, polyvalent (23-valent) (PNEUMOVAX23) for prophylaxis due to his hypogammaglobulinemia (exact doses, site and route of administration, lot number and expiration date were not reported). In July 2018, the patient was referred to pulmonary clinic for a lung biopsy due to concerns about tuberculosis (TB), fungal infections, malignancy and granulomatous disease such as sarcoidosis as a potential underlying cause of the findings. His pulmonary function tests showed moderate reduction of airflow (FEV1/FVC: 59%), normal vital capacity and moderate reduction of diffusion capacity, which were consistent with obstructive lung disease. He underwent bronchoscopy and ultrasound guided endobronchial lymph node biopsy twice in the summer of 2018. A bronchoalveolar lavage (BAL) with multiple node biopsies were negative for bacterial, fungal and TB as a cause of lung disease. Testing was also negative for malignancy. He was started on fluticasone furoate, umeclidinium and vilanterol for further management with improvement in FEV1/FVC ratio. He received isavuconazonium sulfate as treatment for a possible aspergillus infection due to a positive aspergillus galactomannan test. His antifungal treatment was continued for 5 weeks but was stopped in November 2018 secondary to side effects (elevated liver enzymes, nausea, and vomiting).  In December 2018, a repeat CT chest showed progression of multifocal nodularity in his lung and unchanged mediastinal lymphadenopathy. In January 2019, he underwent video-assisted thoracoscopic (VATS) guided lung biopsy of his superior right lower lung that showed lymphoid hyperplasia with interstitial fibrosis, patchy foci of organizing pneumonia, rare giant cells/histiocytes, acute bronchopneumonia and occasional fibrin exudates.  In January 2019, the patient was evaluated in the allergy and immunology clinic for immunodeficiency. A physical examination showed the following: vital signs: blood pressure 110/80, pulse 64/minute, temperature 97 degrees, respiratory rate (RR) 18/minute. Ears, nose, throat (ENT) exam showed bilateral swollen pale nasal turbinate with light yellow drainage. The rest of his physical examination was unremarkable. Repeat laboratory testing was ordered and showed a platelet count of 96K. The tests for comprehensive metabolic panel (CMP), urinalysis, stool ova and parasites and HIV were all negative. An immunoglobulin panel showed an IgM 10 (40-230 mg/dl), IgG 520 (700-1600 mg/dl), IgA 26 (70-400 mg/dl), IgE less than 2 (0-158 mg/dl). Lymphocyte subsets were as followed: absolute lymphocyte: 1126 (1000-4000), CD3: 935 (960-2600) [83% (61-84)], CD4: 586 (540-1660) [52% (32-60)], CD8: 304 (270-930) [27 (13-40%)], CD19: 79 (122-632) [7% (3-22)], CD16 + 56: 90 (70-480) [8% (3-22)]. A lymphocyte mitogen screen showed a low to phytohemagglutinin (PHA) and a normal Concanavalin A (Con A) and Pokeweed Mitogen. A sinus X-ray was remarkable for left maxillary sinus disease showing mucosal thickening. Despite being vaccinated the patient had poor pneumococcal antibody titers with only 2/14 equal or greater than 1.3 microgram/ml being responsive (antibody test abnormal). His tetanus antibody titer was in the protective range of 1.3.  Based on his low IgG and IgA, recurrent infections and failure to respond to pneumococcal vaccination (vaccination failure), the patient was diagnosed with the common variable immunodeficiency (CVID) with coexisting immune thrombocytopenia and granulomatous lymphocytic interstitial lung disease (GLILD). The patient was treated for CVID with intravenous immunoglobulin (IVIG) 30 g every 4 weeks with subsequent increase to 50 g every 4 weeks because of decreasing lung function and decreased platelet count. He remained infection free since November 2018. In January 2020, his follow up chest X-ray and CT chest in showed further widespread lymphadenopathy and nodular lung densities. He was to start treatment with rituximab (RITUXAN) and mycophenolate mofetil for GLILD however while waiting for treatment he tested positive for COVID-19. He slowly recovered without any complication at home and was eventually able to start rituximab (RITUXAN) infusion of 375 mg/m2 weekly for 4 weeks and completed four cycles of therapy without complication. At the time of reporting, he was on maintenance mycophenolate mofetil 1 g and monthly IVIG and was doing well. The outcome of vaccination failure and antibody test abnormal was unknown. The authors considered poor pneumococcal antibody titers and failure to respond to pneumococcal vaccination to be related to the patient's underlying common variable immunodeficiency and pneumococcal vaccine, polyvalent (23-valent) (PNEUMOVAX23).   A copy of the published literature article is attached as further documentation of the patient's experience.