Isolated pulmonary cryptococcosis in an immunocompetent patient presenting with right shoulder pain: a case report and review of the literature

Transcription

1 Hong Kong Journal of Emergency Medicine Isolated pulmonary cryptococcosis in an immunocompetent patient presenting with right shoulder pain: a case report and review of the literature RKH Cheung, F Ng, CT Wong, WMS Tsui Cryptococcosis is an important systemic fungal infection occurring predominantly in immunocompromised patients. We report a case of isolated pulmonary cryptococcosis in an ambulant middle-age lady who presented to the emergency department with right shoulder pain. The clue to lung pathology was right apical haziness best seen in the apical lordotic radiograph. The diagnosis was established by transbronchial lung biopsy. She did not have underlying immunosuppression or extrapulmonary disease. She was closely observed without anti-fungal therapy, and showed radiographic improvement during the five-month period of follow up. (Hong Kong j.emerg.med. 2008;15:43-48) 5 Keywords: Cryptococcus neoformans, immunocompetence, lung disease, thoracic radiography Introduction Cryptococcosis is a systemic infection caused by the encapsulated yeast-like fungus Cryptococcus neoformans. Sometimes it can be severe, disseminated and fatal. In Hong Kong, up till September 2007, it had been one of the fifteen communicable diseases that medical practitioners were encouraged to report to the Centre for Health Protection due to its public health significance. Most cryptococcal infections occur in immunocompromised subjects. The main site of infection is the central nervous system (CNS), followed by the lungs. Isolated pulmonary cryptococcosis is uncommon among immunocompetent individuals. 1,2 Only a few Correspondence to: Cheung Koon Ho, Ralph, MBChB, MRCSEd Tuen Mun Hospital, Accident & Emergency Department, Tsing Chung Koon Road, Tuen Mun, N.T., Hong Kong koonhocheung@yahoo.com.hk Caritas Medical Centre, Accident & Emergency Department, 111 Wing Hong Street, Sham Shui Po, Kowloon, Hong Kong Ng Fu, MRCP(UK), FRCSEd, FHKAM(Emergency Medicine) Caritas Medical Centre, Department of Diagnostic Radiology, 111 Wing Hong Street, Sham Shui Po, Kowloon, Hong Kong Wong Chi Tat, FRCR(UK), FHKCR, FHKAM(Radiology) Kowloon West Cluster Pathology Service, Hong Kong Tsui Man Shan, Wilson, FRCPath, FHKAM(Pathology)

2 44 Hong Kong j. emerg. med. Vol. 15(1) Jan 2008 case reports or studies of pulmonary cryptococcosis in immunocompetent patients have been published in the English literature and in Hong Kong. 3,4 This case report describes an immunocompetent lady having pulmonary cryptococcosis and presenting with right shoulder pain. The disease was nearly overlooked at the initial emergency department visit. Case A 45-year-old ambulant lady attended the emergency department in January 2007 with a chief complaint of right shoulder pain for four days. She had very mild headache, throat discomfort and cough. There was no history of injury. She did not have haemoptysis, shortness of breath, chest pain or weight loss. She had a travel history to Shenzhen two weeks ago. There was no contact history with poultry or pigeons. She had a past history of thyrotoxicosis treated in Shenzhen with carbimazole. Her thyroid function was normal afterwards and the drug was stopped. Otherwise, she enjoyed good past health. She was a non-smoker, and worked as a taxi driver. For the current presentation, she was afebrile. The physical examination did not reveal musculoskeletal causes of shoulder pain or other abnormalities. A chest X-ray (postero-anterior view) was taken in the emergency department. It was commented by the attending doctor as no pneumothorax (Figure 1). She was discharged home with a diagnosis of shoulder joint pain. During retrospective film review by a senior staff of the emergency department, the chest X-ray was noted to have a small shadow over the right apical region. She was called back for reassessment on the next day. The right apical opacity became more obvious in the apical lordotic view X-ray (Figure 2). However, her chest radiograph taken two years ago during body check was normal. She was admitted to the medical ward for work-up of her lung lesion. She had minimal respiratory symptoms, and her shoulder pain subsided quickly with simple analgesics. She remained afebrile all along and the oxygen saturation was 98% on room air. Laboratory tests showed normal white cell and differential counts. The erythrocyte sedimentation rate was 34 mm/hr. Her blood glucose and thyroid stimulating hormone levels were normal. Microscopy of the sputum showed pus cells and the culture yielded normal oral flora, while the sputum for acid-fast bacilli was negative. She was empirically treated with oral co-amoxiclav (Augmentin). However, her radiographic findings did not improve. Figure 1. Chest X-ray showing a small right apical zone shadow. Figure 2. Apico-lordotic view showing right upper zone haziness.

3 Cheung et al./isolated pulmonary cryptococcosis 45 To determine the cause of her lung shadow, fibre-optic bronchoscopy was performed eight days after admission. There was no endobronchial lesion and the mucosa looked normal. However, transbronchial lung biopsy of the right B1 segment showed Cryptococcus infection. Under microscopic examination, there was inflammatory tissue with epithelioid granulomas, multinucleated giant cells, neutrophils and necrotic tissue within which were many fungal yeasts with clear halo around. In Grocott stain, the budding yeasts were highlighted (Figure 3). The biopsy and bronchial aspirate did not show any acid-fast bacilli or malignant cells. The patient spent altogether twelve days in the hospital before discharge. She was asymptomatic. It was decided that antifungal drug should not be given. She was followed up in the medical out-patient clinic, and remained asymptomatic. The chest X-ray five months later showed decreased opacity in the right upper zone (Figure 5). However, she defaulted follow up afterwards. Computed tomography (CT) thorax with contrast was performed, showing a small irregular lesion in the peripheral aspect of the right apex, up to 3 cm in diameter and associated with small satellite nodules. The lesion extended to the pleura, but did not invade the adjacent bone or chest wall. The lesion was compatible with an inflammatory or infective lesion (Figure 4). The serum cryptococcal antigen test was positive (1:8). Regarding pulmonary function test, the ratio of forced expiratory volume in one second to forced vital capacity was 2.45/2.53 L (96.8%). Lumbar puncture was performed to rule out concomitant CNS infection, and showed normal cell count, normal biochemistry (including cryptococcal antigen) and negative culture findings. Blood for the human immunodeficiency virus (HIV) was negative. Figure 4. CT thorax showing an irregular lesion in the peripheral aspect of the right apex, up to 3 cm in diameter. Figure 3. Histopathology of transbronchial biopsy showing poorly encapsulated cryptococcal yeast cells of 5-20 µm in diameter and with narrow-base budding (arrow) (Grocott methenamine silver stain, x 1000). Figure 5. Chest X-ray five months after the initial presentation showing that the lesion in the right upper zone had decreased in density.

4 46 Hong Kong j. emerg. med. Vol. 15(1) Jan 2008 Discussion We report a patient who presented to the emergency department with right shoulder pain for a few days. She was later diagnosed to have pulmonary cryptococcosis. She had no immunosuppressive conditions, and had no exposure to pigeon droppings before. The clinical clue to the disease was haziness at the right apical lung region best visualised in the apical lordotic radiograph. The diagnosis of the infection was made by the presence of Cryptococcus organisms and inflammatory tissues in transbronchial lung biopsy pathology specimens, supported by positive serum cryptococcal antigen titre. She had no extra-pulmonary disease. She had transient symptom of shoulder pain that brought her to the emergency department, but had minimal symptom afterwards. Antifungal therapy was not given, and her lung lesion demonstrated radiological regression during the follow up period. Cryptococcus is a fungus present throughout the world, most commonly being found in bird droppings, soil and decayed wood. The incidence of cryptococcosis in patients who have Acquired Immunodeficiency Syndrome (AIDS) in the USA, Western Europe and Australia has been estimated to be 6-10%. This infection is the most common fungal infection seen in AIDS patients. 5 Cryptococcal infections, including isolated pulmonary cryptococcosis, occur predominantly in immunocompromised patients as opportunistic infections. The common underlying conditions include AIDS, organ transplantation, cytotoxic chemotherapy, prolonged corticosteroid treatment, haematological or advanced malignancies, diabetes mellitus and sarcoidosis. 1,2 Regarding clinical manifestations, although the fungus enters the human body through the lungs, the main site of infection is the CNS, followed by the lungs. Skin, bone, prostate and eye may be involved in disseminated disease. 6,7 CNS involvement by Cryptococcus causes subacute meningitis or meningoencephalitis. These patients present with headache, fever, cranial nerve palsies, coma, or memory loss over weeks. Cryptococcal lung manifestations range from asymptomatic colonisation to lifethreatening pneumonia with acute respiratory distress syndrome. Regarding other body sites, skin infection presents as maculopapule, ulcer, and cellulitis; bone infection presents as osteolytic lesions; eye infection presents as ocular palsies and papilloedema, while prostate involvement is asymptomatic in most cases. 2 Concerning the clinical features of pulmonary cryptococcosis in immunocompetent hosts, there is a wide variety of presentations. In a review by Campbell, symptoms may be absent, or may present as cough (54%), chest pain (46%), increased sputum production (32%), fever (26%), weight loss (26%) and haemoptysis (18%). 8 Bizarre presentation like severe back pain has also been reported. 9 In immunocompetent patients, chest imaging of cryptococcosis can reveal the presence of pulmonary abnormalities, but the findings are non-specific and inconclusive. Chest radiographic features range from single pulmonary nodule to widespread nodular and air-space consolidation. Rarely, they can also present as cavitation, pulmonary infiltrate, hilar and mediastinal adenopathy, and pleural effusion. 3,7 Under computed tomography, the most common finding was pulmonary nodules, whereas lymphadenopathy, consolidation, pleural effusion and cavitation are uncommon. 10 There are many overlapping radiological features among pulmonary cryptococcosis, lung cancer, pulmonary tuberculosis, bacterial pneumonia and other mycosis. In our patient, extension of the right apical lung lesion to the pleura shown in the CT may explain the pain that was perceived in the right shoulder. The diagnosis of pulmonary cryptococcosis is based upon histopathologic detection of the organism at lung biopsy or a positive culture from the respiratory specimen. Serum cryptococcal antigen plays an adjunctive role. 11 Our patient had cryptococcal infection rather than colonisation, as evidenced by granulomatous reaction and the presence of Cryptococcus organisms in the alveolar spaces of the pathology tissue specimen.

5 Cheung et al./isolated pulmonary cryptococcosis 47 With regard to treatment, antifungal therapy (usually amphotericin B, fluconazole or itraconazole) is indicated for disseminated cryptococcosis, CNS involvement and immunocompromised patients. 5 For isolated pulmonary cryptococcosis in immunocompetent patients, treatment is controversial. Consideration for administering anti-fungal drug has to weigh between the benefits of the drugs in preventing disease progression and potential drug toxicities. Previous literature suggested that these patients did not require treatment. It was built on the basis of minimal disease dissemination, reports of spontaneous resolution, and risk of treatment with empirical antifungal therapy. 1,12-14 However, it was observed that some of those patients without treatment might progress to overwhelming cryptococcal pneumonia with fatal outcome or central nervous system dissemination. 15,16 Therefore, some author questioned the wisdom of observing immunocompetent patients without therapy. 17 The current recommendation suggests that for immunocompetent patients with isolated cryptococcal pneumonia, observation with careful follow up is a reasonable option for those without significant symptoms. If the patient is symptomatic, antifungal drug should be used. 18 Therefore, it was justifiable to treat our patient by either observing carefully or using oral fluconazole as a first-line drug. Since there is no consensus on the optimal duration of observation for those without drug treatment, it may be better to call back our patient to allow a longer period of follow up. This report brings out a few points worthy of note: (1) Diagnosis of pulmonary cryptococcosis is important. The disease can be disabling and fatal, and warrants a search for underlying immunosuppresion and CNS involvement. If the patient is immunocompromised or has CNS disease, antifungal drugs should be used. For asymptomatic patients, close observation is a basic requirement. (2) The clinical feature of pulmonary cryptococcosis is variable and the patient may present with shoulder pain. (3) Retrospective radiograph review reduces errors in emergency departments. Subtle signs in chest X-rays may be a clue to the disease. The apical lordotic view is useful in visualising the apical lung region. Conclusion Pulmonary cryptococcosis in the immunocompetent host represents an uncommon form of cryptococcal infection. Our patient, without underlying immunodeficiency, was diagnosed to have isolated pulmonary cryptococcosis starting with a complaint of right shoulder pain and subtle finding on the initial chest X-ray. She was observed and the chest X-ray done at five months during follow up showed regression of the haziness. The apical lordotic chest X-ray should be considered in case of subtle apical lung lesion. Acknowledgement We are grateful to Dr CK Leung, Patrick, for his advice on this manuscript. References 1. Kerkering TM, Duma RJ, Shadomy S. The evolution of pulmonary cryptococcosis: clinical implications from a study of 41 patients with and without compromising host factors. Ann Intern Med 1981;94(5): Perfect JR. Cryptococcus neoformans. In: Mandell GL, Bennett JE, Dolin R. Principles and practice of infectious diseases. 6th ed. Philadelphia, PA: Elsevier/ Churchill Livingstone; 2005: Yang CJ, Hwang JJ, Wang TH, Cheng MS, Kang WY, Chen TC, et al. Clinical and radiographic presentations of pulmonary cryptococcosis in immunocompetent patients. Scand J Infect Dis 2006;38(9): Lam CL, Lam WK, Wong Y, Ooi GC, Wong MP, Ho JC, et al. Pulmonary cryptococcosis: a case report and review of the Asian-Pacific experience. Respirology 2001;6(4): Hoepelman AIM. Opportunistic fungi. In: Cohen J, Powderly W, editors. Infectious diseases. 2nd ed. Edinburgh: Mosby;2004: Ryan KJ, Ray CG. Sherris medical microbiology: an introduction to infectious diseases. 4th ed. New York: McGraw-Hill;2004: Cox GM, Perfect JR. Cryptococcal pneumonia. UpToDate. [updated 2007 Jan 8; cited 2007 Sep 6]. Available from: 8. Campbell GD. Primary pulmonary cryptococcosis. Am Rev Respir Dis 1966;94(2): Iwasaki Y, Tominaga M, Kuroki S, Kato O. Case of primary pulmonary cryptococcosis accompanied by

6 48 Hong Kong j. emerg. med. Vol. 15(1) Jan 2008 severe back pain. Nihon Kokyuki Gakkai Zasshi 2005; 43(2): Lindell RM, Hartman TE, Nadrous HF, Ryu JH. Pulmonary cryptococcosis: CT findings in immunocompetent patients. Radiology 2005;236(1): dos Santos JWA, Neves KR, Santos FP, Gazzoni MF, Dalcin TC, Fagundes AL, et al. How could pulmonary cryptococcosis in immunocompetents be suspected? Report of 6 cases. Respir Med Extra 2006;2(2): Aberg JA, Mundy LM, Powderly WG. Pulmonary cryptococcosis in patients without HIV infection. Chest 1999;115(3): Nadrous HF, Antonios VS, Terrell CL, Ryu JH. Pulmonary cryptococcosis in nonimmunocompromised patients. Chest 2003;124(6): Wassmann S, Nickenig G, Böhm M. Long QT syndrome and torsade de pointes in a patient receiving fluconazole. Ann Intern Med 1999;131(10): Robinson GR 2nd. Images in clinical medicine. Severe cryptococcal pneumonia. N Engl J Med 1995;332(26): Núñez M, Peacock JE Jr, Chin R Jr. Pulmonary cryptococcosis in the immunocompetent host. Therapy with oral fluconazole: a report of four cases and a review of the literature. Chest 2000;118(2): Sarosi GA. Cryptococcal lung disease in patients without HIV infection. Chest 1999;115(3): Saag MS, Graybill RJ, Larsen RA, Pappas PG, Perfect JR, Powderly WG, et al. Practice guidelines for the management of cryptococcal disease. Infectious Diseases Society of America. Clin Infect Dis 2000;30(4):710-8.