Pulmonary Histoplasmosis in a patient with Cough, Dyspnea, Pulmonary Nodule and Rheumatologic Manifestations: Case Report and Review

Abstract

In this case report we describe a case of pulmonary histoplasmosis in a healthy adult female living in Kentucky. The patient presented with two months history of poly-arthralgia and myalgia, intermittent dry cough, chest tightness, exertional dyspnea, malaise, fatigue and one week history of skin rash. She did not respond to broad-spectrum antibiotic therapy and she also had extensive endocrine and rheumatologic work up that was negative. A diagnosis of histoplasmosis was established based on radiological findings as well as endobronchial ultrasound-guided transbronchial needle aspiration cytology (EBUS-TBNA) of mediastinal lymph nodes demonstrating necrotizing granuloma with fungal stains positive for Histoplasma. Patient showed significant clinical improvement on antifungal treatment. Since symptoms of histoplasmosis are often similar to the symptoms of community acquired pneumonia, other lung infections or malignancy, our case highlights the importance of maintaining a high index of suspicion and appropriate radiological, microbiology, and histologic evaluation especially in patients who live in or have traveled to areas endemic for histoplasmosis and are not responding to antibiotic therapy. Early diagnosis coupled with prompt initiation of antifungal treatment may lead to favorable outcomes. DOI: 10.18297/jri/vol2/iss2/8 Received Date: July 2, 2018 Accepted Date: August 1, 2018 Website: https://ir.library.louisville.edu/jri Copyright: ©2018 the author(s). This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Affiliations: 1St. Elizabeth Physicians, Infectious Disease, Crestview Hills, KY, USA *Correspondence To: Johnson Britto, MD, MPH Work Address: St. Elizabeth Physicians, Infectious Disease, Crestview Hills, KY, USA Work Email: johnsypb@gmail.com 45 ULJRI Vol 2, (2) 2018 REVIEW ARTICLE and oxygen saturation 98% on room air. On physical exam, she had a skin rash with description as noted above, otherwise she had no respiratory distress, no lymphadenopathy, no joint swelling or tenderness. Examination of the respiratory system, cardiovascular system, abdomen, central nervous system was noted to be unremarkable. Initial diagnostic laboratory work up showed leucocyte count of 9,100 cells/mm3 (no eosinophilia), hemoglobin 14.3 g/dl, hematocrit 44.3% and platelet count 295,000/mm3. Serum electrolytes, renal function, liver function tests, and lipid screen were normal. Urinalysis was negative for protein or blood. Rapid Streptococcus group A antigen test and Influenza test for A & B antigens were negative. Chest X-ray (CXR) showed new linear opacity best seen on the lateral view in the region of the lingula with differential of fluid or fat within the major fissure versus small infiltrate in the lingula (Figure 2). High resolution chest computed tomographic (CT) scan was obtained revealing a linear density seen on the initial chest x-ray corresponding to a small amount of fat seen extending into the right major fissure, otherwise no residual infiltrate was noted. In the right lower lobe, posteriorly, there was a nonspecific sub-pleural nodule measuring about 8 mm in size. It was new since the prior chest computed tomographic (CT) scan obtained seven years ago. Remaining lungs were clear with no evidence of interstitial lung disease, ground-glass infiltrate, bronchiectasis, honeycombing or air trapping. Right para-tracheal node was present. No other mediastinal, hilar, or axillary nodes were seen. (Figure 3). PET/CT skull base to mid-thigh was obtained that showed minimal level of metabolic activity at the site of the right lung pulmonary nodule, and hypermetabolic sub-carinal and right para-tracheal lymph nodes (Figure 4). An infectious process, including possible fungal disease, or malignancy were suspected. 46 ULJRI Vol 2, (2) 2018 Fig. 1 Skin rash consisting of multiple scattered targetoid appearing erythematous papules of size 0.5-1.0 cm on bilateral lower extremities. Fig. 2 Initial Chest X-ray (CXR) PA and Lateral showing linear opacity best seen on the lateral view in the region of the lingula with differential of fluid or fat within the major fissure versus small infiltrate in the lingula. Fig. 3 Chest computed tomographic (CT) scan showing sub-pleural nodule measuring about 8 mm in size in the posterior aspect of right lower lobe. A referral to dermatology was made and a punch biopsy of the skin rash from her right dorsal thigh was performed. Hematoxylin & Eosin (H &E) stained section of the specimen showed histiocytes in the dermis arranged in rings, and distributed in discrete foci throughout the dermis. Granular and fibrillary mucinous material was present in the foci of a histiocytic aggregation. In addition, there was superficial and deep perivascular lymphocytic infiltrate, with likely diagnosis of granuloma annulare. She was placed on five week course of a low dose oral prednisone taper with some improvement noted in her skin rash and joint symptoms. During the subsequent weeks, due to non-resolution and persisting nature of her symptoms, she had several follow up visits with her primary care physician. She received several rounds of different oral antibiotics without significant improvement in her symptoms. In an effort to establish a diagnosis, extensive laboratory work up including rheumatologic/autoimmune and endocrine work up was performed which included CPK, aldolase, lactic acid, complement fixation tests, rheumatoid factor, antinuclear antibody, anti-neutrophil cytoplasmic antibody screen (MPO & PR3), SS-A/Ro and SS-B/La, ENA antibodies, Sm/RNP, dsDNA, CCP antibody, anti-glomerular basement membrane antibody, monoclonal protein, thyroid function panel, thyroid peroxidase (TPO), thyroglobulin antibody, parathyroid hormone (PTH intact), Insulin-Like Growth I (IGF1), adrenocorticotropic hormone (ACTH), serum cortisol, serum ferritin, iron/UIBC/transferrin saturation, vitamin B1, B6, B12 and Vitamin D (25-Hydroxy) levels and ACE level. All of the above laboratory work up was unremarkable. C-reactive protein (CRP) was mildly elevated at 6.44 (<5.0 mg/L is considered normal), Erythrocyte Sedimentation Rate (ESR) was normal. Additional laboratory work up including human immunodeficiency virus serology, syphilis screen, acute hepatitis panel, urine Histoplasma antigen, serum (1→3)-β-Dglucan, serum fungal serology by immunodiffusion, fungal blood cultures, serum interferon gamma release assay, were also negative. A bronchoscopy was performed and it did not reveal any endobronchial lesions. Endobronchial ultrasound (EBUS) scope was introduced and a systematic survey of the mediastinal lymph nodes was conducted. This revealed enlarged lymph nodes in stations 7 and 11R. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) of mediastinal lymph nodes was performed. The adequacy of the specimens was confirmed with rapid onsite pathology. Following this, endobronchial specimens, endobronchial brushing and bronchoalveolar lavage (BAL) were obtained from right lower lobe, right and left upper lobes. Biopsy of the mediastinal lymph nodes, bronchial brushing & BAL cytology were negative for malignancy. Stains for acidfast bacilli were negative. Stained section of mediastinal lymph node showed numerous lymphocytes, histiocytes, many multinucleated giant cells, forming necrotizing granuloma. Grocott’s Methenamine Silver (GMS) stain also revealed the presence of small uniform black yeast forms of approximately 2 to 4 μm in size (Figure 5). Some of these yeast forms showed narrow-based budding, overall morphology was consistent with Histoplasma. Gram’s stain of BAL and biopsy specimens showed rare while blood cells, no organisms. Aerobic, anaerobic, acid fast bacilli and fungal cultures were negative. BAL viral respiratory panel was negative. The patient was started on oral itraconazole for twelve weeks. She tolerated the treatment well and successfully completed her 12-week course of itraconazole for histoplasmosis with significant improvement in her symptoms. 47 ULJRI Vol 2, (2) 2018 Fig. 4 PET/CT skull base to mid-thigh showing hypermetabolic subcarinal and right para-tracheal lymph nodes. Fig. 5 Photomicrograph: Grocott’s Methenamine Silver (GMS) stained section of mediastinal lymph node showing necrotizing granuloma containing small uniform black yeast forms of approximately 2 to 4 μm size with narrow based budding consistent with Histoplasma (GMS stain, 60X).