Disseminated Talaromycosis Leelasiri, A, et al.

Greater Mekong Subregion Case Report GMSMJ Medical Journal

A Young Man with High-grade Fever and HIV Apichai Leelasiri, M.D.1, Tawatchai Pongpruttipan, M.D.2 1Department of Medicine, School of Medicine, Mae Fah Luang University, Chiang Rai 57100, Thailand 2Department of Pathology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand Received 11 March 2021 • Revised 24 March 2021 • Accepted 30 March 2021 • Published online 1 May 2021

Abstract: A 23-year-old man, a hilltribe in northern Thailand with HIV infection but poor compliance to antiviral treatment presented with acute onset of fever, fatigue with palpitation. He also experienced easily fatigue and tiredness for 1 month. He went to local hospital and was treated symptomatically without any improvement. Then he went to another hospital for management. Initial investigation showed and thrombocytopenia. The examination revealed -like microorganism with binary fission. Final diagnosis of disseminated talaromycosis (penicillosis) was made. So, in case of fever of unknown origin in HIV-infected patients, bone marrow examination should be performed which can be helpful for definite diagnosis.

Keywords: HIV infection, Disseminated talaromycosis, High-grade fever

Introduction which can cause fever. The problem of Untreated HIV-infected patients physicians taking care of these patients is usually have fever which some of them are unable to diagnose the causative infection. initially unable to identify the causes. Most Some physicians use therapeutic diagnosis of them are from with antituberculosis drugs. This method (OI) due to bacteria, viruses, fungi, and can cause delayed diagnosis and increased protozoa. In Thailand, there are high morbidity and mortality. Prompt investiga- incidence of some OI such as mycobacterial tion with rapid result is needed especially infection ( and atypical in resource-restricted rural hospital. mycobacterium), cryptococcal menin- gitis, disseminated and Case Presentation talaromycosis (penicillosis). Although A 23-year-old man, a hilltribe in other such as Pneumocystis northern Thailand with HIV infection but carinii, toxoplasmosis, parvovirus B19 poor compliance to antiviral treatment and CMV infection can be encountered. presented with acute onset of fever, fatigue Besides infection, HIV-infected patients are with palpitation and non-productive cough also having higher incidence of lymphoma for 1 month. He had no diarrhea, nausea

Corresponding author: Apichai Leelasiri, M.D. GMSMJ 2021; 1 (2): 93-98 School of Medicine, Mae Fah Luang University, Chiang Rai 57100, Thailand E-mail: [email protected] @2021 GMSMJ. Hosting by Mae Fah Luang University. All rights reserved

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or vomiting. He went to the local hospital 0.3 mg/dL, direct bilirubin 0.1 mg/dL, AST and received symptomatic treatment 36 U/L, ALT 23 U/L, ALP 59 U/L, CD4 without improvement. So, he came to 36/μL. Chest x-ray: no pulmonary another hospital for management. He infiltration. Ultrasound of whole abdomen: had previous admission to the hospital with diffuse increased 3 months prior to this admission because parenchymal echogenicity and of anorexia, weight loss, non-productive with wedge shaped patchy hypoecho- cough, low grade fever and was diagnosed genicity, possible infarction and several AIDS with pneumocystis carinii infection. enlarged lymph nodes along periportal On admission to this hospital, vital signs regions. Review of blood smear found mild showed body temperature of 37.8oC (after hypochromic red blood cells with frequent taking paracetamol), heart rate 120/minute, polychromasia. Bone marrow aspiration blood pressure 113/74 mmHg, respiration and was performed. The finding 20/min, height 159 cm, weight 44 kgs with revealed hypercellular bone marrow with BMI of 17.4 kg/m2. He was moderately intracellular yeast-like organisms, some had anemic without jaundice. He had no binary fission compatible with talaromycosis palpable but palpable (penicillosis) as shown in Figure 1. So, the liver and spleen 4 cm. and 6 cm. respectively patient was started with below costal margins. No any skin lesion was 1 mg/kg on the admission day. On the detected. Investigation revealed Hct 26%, following day, he was doing better with Hb 8.0 g/dL, WBC 5.39 x 109/L, PMN 76%, fever down. He subsequently received oral L 9%, M 3%, E 11%, platelet 100.0 x 109/L, fluconazole. A week later, blood culture for MCV 70 fL, MCH 23 pg, BUN 14 mg/dL, was reporting Penicillium marneffei. Cr 0.77 mg/dL, GFR 128 mL/min, Na 126 The bone marrow biopsy came back 1 week mmol/L, K 3.9 mmol/L, Cl 94 mmol/L, CO2 later and revealed talaromyces as in Figure 25 mmol/L, total protein 6.6 g/dL, albumin 2, 3 and 4. 3.2 g/dL, globulin 3.4 g/dL, total bilirubin

Figure 1 Bone marrow smear shows intracellular yeast-like organisms with binary fission consistent with talaromycosis (penicillosis). (left x 40, right x100)

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Figure 2 The bone marrow biopsy x40 shows marked hypercellularity.

Figure 3 The bone marrow biopsy x 100 shows many aggregates containing many yeast-like particles.

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Figure 4 GMS stain in the bone marrow highlights many oval-shaped without budding but occasional binary fission (in circle).

Discussion myelophthisis, this could not totally exclude This patient was a 23-year-old infection or malignancy in the bone marrow. hilltribe man with acute onset of fever, If we were waiting for culture result or fatigue with palpitation. He was also therapeutic trial with antituberculosis drugs, diagnosed HIV infection with possible this could be more harmful because of pneumocystis carinii pneumonia 3 months delayed diagnosis and adverse drug reaction. ago with poor compliance to antiretroviral Bone marrow examination in this patient was treatment. By physical examination, he justified and could make rapid diagnosis. had anemia, hepatosplenomegaly without Talaromycosis1 (formerly Penicilliosis2) any obvious skin lesions. So, differential is an infection caused by the fungus diagnosis should be opportunistic infections . Talaromycosis such as mycobacterial infection both TB commonly affects people who live in (tuberculosis) and MAC (mycobacterium Southeast Asia3, southern China4, or eastern avium complex), cryptococcal infection India. Most people who get talaromycosis although having no significant headache have defective immune function, especially of stiff neck, other disseminated fungal HIV/AIDS5. In Thailand, this infection infection and because he had intraabdominal usually found in northern part6 such as lymphadenopathy, lymphoma should be Chiang Rai or Chiang Mai. Patients with in the differential diagnosis. Initial CBC this infection mostly experience high- showed anemia and thrombocytopenia, grade fever, anorexia, weight loss, painless although blood smear did not show skin lesion. Some patients have cough,

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difficulty breathing, diarrhea, abdomi- 2. Vanittanakom N, Cooper CR, Jr., Fisher nal pain, lymphadenopathy and palpable MC, Sirisanthana T. Penicillium hepatosplenomegaly7. marneffei infection and recent In people with HIV-infected patients, advances in the epidemiology and talaromycosis is more likely to spread molecular biology aspects. Clin through the blood and affect the whole body. Microbiol Rev 2006; 19: 95-110. Skin lesions due to talaromycosis usually 3. Supparatpinyo K, Khamwan C, have a small dent in the center. In non-HIV Baosoung V, Nelson KE, Sirisanthana infected patients, talaromycosis commonly T. Disseminated Penicillium marneffei affects the lungs, liver, and mouth. Some- infection in Southeast Asia. Lancet times it spreads through the blood and 1994; 344: 110-3. affects the whole body. Patients with other 4. Zheng J, Gui X, Cao Q, et al. A immune dysfunction such as cancer, organ clinical study of acquired immuno- transplant, adult-onset immunodeficiency deficiency syndrome associated syndrome and other autoimmune diseases Penicillium marneffei infection from can be infected with talaromycosis8. a non-endemic area in China. PLoS Bone marrow examination can identify One 2015; 10: e0130376. this organism in macrophages or neutrophils. 5. Wong SYN, Wong KF. Penicillium Histoplasma and talaromyces are yeast like marneffei infection in AIDS. Patho Res organism. Both look similar, but talaromyces Int 2011; 2011: Article ID 764293. has typical binary fission. However, definite 6. Chariyalertsak S, Sirisanthana T, diagnosis requires fungal culture. Supparatpinyo K, Praparattanapan J, Talaromycosis is usually treated with Nelson KE. Case-control study of risk amphotericin B for two weeks, followed by factors for Penicillium marneffei or given by mouth infection in human immunodeficiency for 10 weeks. Patients with HIV infection virus-infected patients in northern should receive antiretroviral one week after Thailand. Clin Infect Dis 1997; 24: starting amphotericin B9. 1080-6. 7. Sirisanthana T. Penicillium marneffei Conclusion infection in patients with AIDS. Emerg The authors reported case of dissemi- Infect Dis 2001; 7: 561. nated Talaromyces (Penicillium) marneffei 8. Kawila R, Chaiwarith R, Supparatpinyo infection in HIV-infected patient. We suggest K. Clinical and laboratory characteris- bone marrow examination and culture for tics of Penicillium marneffei among diagnosis fever of unknown origin in this patients with and without HIV infection setting. in Northern Thailand: a retrospective study. BMC Infect Dis 2013; 13: 464. Conflict of interest 9. Supparatpinyo K, Nelson KE, Merz The author has declared no conflict of WG, et al. Response to interest. therapy by human immunodeficiency virus-infected patients with dissemi- References nated Penicillium marneffei infections 1. Yilmaz N, Visagie CM, Houbraken J, and in vitro susceptibilities of isolates Frisvad JC, Samson RA. Polyphasic from clinical specimens. Antimicrob taxonomy of the genus Talaromyces. Agents Chemother 1993; 37: 2407-11. Stud Mycol 2014; 78: 175-341.

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