Hypercalcemia, diffuse infiltrates, and cough in a patient with multiple myeloma and chronic kidney disease

SESSION TITLE: Chest Infections Case Report Posters 3 SESSION TYPE: Case Report Posters PRESENTED ON: 10/09/2023 12:00 pm - 12:45 pm INTRODUCTION: Pulmonary infections in immunocompromised hosts are common and focusing diagnostic testing to confirm microbiologic diagnosis is paramount. CASE PRESENTATION: A 65-year-old man with IgG-lambda multiple myeloma and chronic kidney disease undergoing treatment with Daratumumab, Pomalidomide, and Dexamethasone, presented with fever, non-productive cough, fatigue, and weight loss. Cough started after exposure to powder after mixing cement one month prior. Physical exam was unremarkable. Initial labs were notable for hypercalcemia (calcium 11.6 mg/dL, ionized calcium 1.56 mmol/L), elevated 1,25-dihydroxyvitamin D (90 pg/mL), and normal intact parathyroid hormone, parathyroid hormone-related peptide (PTHrP), and 25-hydroxyvitamin D. CT chest demonstrated diffuse micronodules with interstitial thickening and patchy ground glass opacities. An eosinophilic bronchoalveolar lavage (34%) yielded negative cultures. Infectious workup rendered negative results, including histoplasma antigen in serum and urine. Despite empiric antibiotics, he remained symptomatic with persistent imaging findings. Bronchoscopy with transbronchial biopsies of the right upper lobe showed granulomatous inflammation and a rare cluster of silver stain structures compatible with histoplasmosis. The patient was treated with steroids and 12 weeks of itraconazole with improvement in symptoms and imaging. DISCUSSION: The etiology of our patient's illness was elusive until biopsy confirmed the diagnosis. Hypersensitivity pneumonitis, drug-related pneumonitis, pneumoconiosis, and infection were also within the differentials, but hypercalcemia provided an additional clue to the final diagnosis. Although multiple myeloma and chronic kidney disease potentially offered an explanation, his multiple myeloma was clinically improving, and calcium levels before and during treatment had been within normal limits. Further, there were no new osteolytic or bone metastases on imaging, and PTHrP was also normal. Although initial testing for urine, serum, and staining of bronchoalveolar lavage were all negative, there was a high suspicion for atypical infection given his immunocompromised state, symptoms, and chest imaging findings. Antibody assays can be falsely negative in immunosuppressed patients and chest imaging findings in patients with histoplasmosis may be non-specific. Silver stain of a biopsy or bronchoalveolar lavage will show macrophages filled with yeast cells and buds from a narrow base and the associated pathology of histoplasmosis is that of a caseating granuloma with central necrosis. CONCLUSIONS: Histoplasmosis can present with mild symptoms or life-threatening disseminated disease. Hypercalcemia may suggest granulomatous process if other etiologies are excluded. Antibody assays for histoplasmosis may be falsely negative in immunosuppressed patients, and additional bronchoscopic studies (lavage, biopsy) can increase the diagnostic yield. REFERENCE #1: Gulati M, Saint S, Tierney LM Jr. Clinical problem-solving. Impatient inpatient care. N Engl J Med. 2000;342(1):37-40. doi:10.1056/NEJM200001063420107. REFERENCE #2: Sharma OP. Hypercalcemia in granulomatous disorders: a clinical review. Curr Opin Pulm Med. 2000 Sep;6(5):442-7. doi: 10.1097/00063198-200009000-00010. PMID: 10958237. REFERENCE #3: Liu JW, Huang TC, Lu YC, Liu HT, Li CC, Wu JJ, Lin JW, Chen WJ. Acute disseminated histoplasmosis complicated with hypercalcaemia. J Infect. 1999 Jul;39(1):88-90. doi: 10.1016/s0163-4453(99)90108-1. PMID: 10468135. DISCLOSURES: No relevant relationships by Philip Angelides No relevant relationships by Saadia Faiz No relevant relationships by Oriana Salamo