Diffuse Lung infiltrates in a smoker with HIV infection
We acknowledge Dr.Philip Xiao MD (Dept of Pathology, The Brooklyn Hospital Center) for providing the photographs of histopathology slides used in this presentation.
ABG-Arterial Blood Gas H&E-Hematoxylin eosin
DLCO-Diffusing capacity of the lung LCH-Langerhans’ Cell Histiocytosis
for carbon monoxide PCO2-Partial pressure of CO2
FEF25-75%-Forced expiratory flow at PO2-Partial pressure of O2
25-75% of the pulmonary volume PFT-Pulmonary function Test
FEV1-Forced Expiratory Volume in 1 sec RV-Residual volume
FVC-Forced vital capacity TLC-Total lung capacity
Opportunistic lung infections are frequently considered when patients with HIV infections present with respiratory symptoms and abnormal Chest. Though fiberoptic bronchoscopy with bronchoalveolar lavage is diagnostic for infectious etiologies, Lung biopsies preferably surgical lung biopsies are required to diagnose non-infectious lung diseases and to help guide appropriate therapy
A 58 year old African American female presented with 2 week history of progressive dyspnea, non-productive cough, fever with night sweats and weight loss of 35 pounds over a period of 8 to 10 months. She denied chest pain and hemoptysis. Significant medical history included hypertension, diabetes mellitus, COPD, an inadequately treated latent tuberculosis infection and a sexually acquired HIV infection. She was an active smoker for 44 years. She was non-compliant with antiretroviral medications and sulfamethoxazole / trimethoprim for prophylaxis.
On physical exam, there was no palpable lymphadenopathy; Lungs were clear to auscultation, cardiovascular exam was normal with no added sounds. Chest X-ray (Fig.1) revealed diffuse interstitial nodular and cystic lung infiltrates predominantly in the upper lobes bilaterally with no pleural effusion. ABG done on room air was Ph-7.49, PCO2-39mmHg, PO2-70mmHg, HCO3-30mmHg, O2 sat-94%. The CD4 count was 194 with a viral load of 2199 copies. Three sputum smears were negative for mycobacteria.
CT scan of chest (Fig.2) showed emphysematous changes with diffuse bilateral pulmonary nodules predominantly in the upper lobes and no significant mediastinal lymph nodes. Pulmonary function test showed FEV1-1.94L (82%), FVC-2.69L (91%), FEV1/FVC-72%, FEF25-75%- 1.34L/sec (43% ), TLC- 4.78L (81%), RV- 2.09L (94%) and DLCO- 9.9ml/mmHg/min (38%) with no bronchodilator response.
She refused bronchoalveolar lavage. Patient underwent Video Assisted Thoracoscopy and surgical lung biopsy of Right lung. Specimens were taken from upper, middle and lower lobe.
RADIOLOGY AND PATHOLOGY
CT of chest
Immuno Stain 1
Immuno stain 2
Lung Tissue 1
Lung tissue 2
Microscopic examination with H&E stain (Fig.3 & 4) showed pulmonary macrophages, mild interstitial inflammation and mild to moderate interstitial fibrosis with patchy scarring and anthracotic pigment deposition. Multiple interstitial nodules comprising of central areas of Langerhans type histiocytes, with eosinophils and other inflammatory cells were noted. The immunohistochemical stains for S100 (Fig.5) and CD1a (Fig.6) were strongly positive and consistent with Langerhans’ cells. Special stains (Ziehl-Neelsen & Gomori methanamine silver) failed to reveal any mycobacteria, fungi or pneumocystis jiroveci.
Pulmonary Langerhans cell histiocytosis (PLCH), also previously called as eosinophilic granuloma of the lung, or pulmonary histiocytosis X, is a rare disease and constitutes only 3-5% of biopsy confirmed chronic diffuse interstitial lung disease1. It is primarily seen in young adults between 20-40 years of age; 90-95% of patients are smokers, and many are heavy smokers2.
Clinical manifestation: The most common symptoms include nonproductive cough, dyspnea, pleuritic chest pain, fatigue, weight loss, fever & recurrent spontaneous pneumothorax
Radiology: The combination of multiple cysts and nodules, with a mid to upper zone predominance, and interstitial thickening, preservation of lung volume and costophrenic angle sparing in a young smoker is characteristic of PLCH3. Differential diagnosis depends on the stage of the disorder. When only small nodules are identified, tuberculosis, fungal infection, sarcoidosis, silicosis are to be considered. When both nodules and small cysts are present, the differential diagnosis includes lymphocytic interstitial pneumonitis, neoplasm (eg, cavitary metastases) and nodular disease (of any etiology) with coexistent emphysema. If only cysts are present, then the differentials include lymphangioleiomyomatosis, Pneumocystis jiroveci pneumonia with cyst formation and central acinar emphysema.
Treatment: Smoking cessation usually stabilizes the symptoms in most patients4. Glucocorticoids and cytotoxic agents are of limited value. No treatment has been confirmed to be useful, and no double-blind therapeutic trials have been reported.
Our patient has remained clinically stable over a follow up period of 2 years without any specific therapy. Follow up PFT done 2 year later revealed FEV1-1.92L (82%), FVC-2.95L (101%), FEF25-75%- 0.93L/sec (30%), FEV1/FVC%-65%, TLC-5.24L (89%), RV-2.29L (102%) and DLCO- 9.2ml/mmHg/min (38%).
Four cases of extra pulmonary LCH in association with HIV that have been reported 5,6,7,8. To our knowledge this is the first case of PLCH in association with HIV to be reported. The cause of this association is not explained.
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