Penicilliosis Marneffei in HIV Negative Children: Three Case Reports
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8447 Case Report Penicilliosis marneffei in HIV negative children: three case reports Jiang-Hua Fan1, Hai-Yan Luo1, Long-Gui Yang1, Meng-Ying Wang2, Zheng-Hui Xiao1 1Emergency Center of Hunan Children’s Hospital, Changsha, China; 2School of Pediatrics, Nanhua University of Hunan, Hengyang, China Correspondence to: Hai-Yan Luo. Emergency Center of Hunan Children’s Hospital, No. 86, Ziyuan Road Yuhua District, Changsha 410007, China. Email: [email protected]. Abstract: This study aimed to report the clinical characteristics of penicilliosis marneffei (PSM) in three children negative to HIV. Three children were diagnosed with PSM in the Department of Emergency Medicine, Hunan Children’s Hospital between February 2016 to July 2020. The clinical characteristics, laboratory findings, and concomitant diseases were recorded, and the related literatures were reviewed. The clinical characteristics and treatment of PSM were reported according to our experience and literature review. The initial symptom was right lower limb mass in 1 child (first) who developed fever and cough about 1 month later and then was misdiagnosed with tuberculosis. The other child (second) had a fever, reductions in red blood cells, white blood cells and platelets, hepatosplenomegaly and lymphadenectasis. The third child had fever, jaundice, multiple organ dysfunction syndrome (MODS), hepatosplenomegaly and lymphadenectasis. The first child (Case 1) had STAT1 gene mutation on genetic examination, and the second child (Case 2) had history of onychomycosis and oral ulcer, the third child (Case 3) had STAT3 gene mutation on genetic examination, diagnosed with Hyperimmunoglobulin E syndromes (HIES). PSM was confirmed in all cases by the culture bone marrow. All three cases were diagnosed through medulloculture. Case 1 and Case 2 also had lymph node biopsy. Case 3 had sputum culture and bronchoalveolar lavage fluid (BALF). The first child was intravenously administered with voriconazole and amphotericin B liposomes, and orally administered with itraconazole for maintenance therapy, which was discontinued 1 year later. The second child was administered with voriconazole intravenously and thereafter orally for a total of 7 months. Recurrence was not observed. The third child was given amphotericin B for 2 days (discontinued due to liver dysfunction), and intravenous voriconazole for 4 days. The patient gave up therapy finally. In conclusion, HIV negative children can also develop PSM, and may be related to the STAT1/STAT3 gene mutation. For children having no response to antibiotic or antiviral therapy, bacterial/fungal culture or biopsy should be performed as soon as possible to confirm the diagnosis, and physicians should actively identify the underlying diseases of PSM patients, which is beneficial for the early diagnosis, early treatment and improvement of prognosis Keywords: Penicilliosis marneffei (PSM); STAT1/STAT3 gene mutation; HIV negativity; child Submitted Oct 17, 2020. Accepted for publication Mar 25, 2021. doi: 10.21037/apm-20-2056 View this article at: http://dx.doi.org/10.21037/apm-20-2056 Introduction are complex with a high mortality, and thus it is often misdiagnosed. In recent years, the incidence of invasive Penicilliosis marneffei (PSM) is a rare deep fungal disease fungal infections is increasing in children, disseminated caused by Penicillium marniffei (PM). It is frequently found PSM is rarely reported, and the disseminated PSM related in HIV-positive or immunosuppressive patients (1), subjects to immunodeficiency due to STAT1 and STAT3 gene with normal immunity are not likely to develop PSM, mutation is even rarer in children. In the past 4 years, 3 and it is even rarer in children (2). PSM mainly involves HIV negative children were diagnosed with disseminated the mononuclear macrophages, its clinical manifestations PSM in our hospital. Herein, we reported our experience © Annals of Palliative Medicine. All rights reserved. Ann Palliat Med 2021;10(7):8437-8447 | http://dx.doi.org/10.21037/apm-20-2056 8438 Fan et al. PSM in children on the early diagnosis and differential diagnosis of PSM suggesting infectious lesions with pathological fracture. after reviewing literatures, which may provide evidence Findings after lymph node biopsy were consistent with for future diagnosis of PSM in children. We present the fungal infection. Bone marrow culture in our hospital and following article in accordance with the CARE reporting another hospital showed Marneffe penicillin (Figure 1). checklist (available at http://dx.doi.org/10.21037/apm-20- Case 2 (Table 1): a girl aged 4 years and 10 months was 2056). admitted due to fever and cough for 14 days. She developed fever as high as 40.2 , and occasional cough was present. She visited local hospital 9 days ago, and routine blood test Case presentation ℃ 9 showed white blood cell count was 3.97×10 /L; hemoglobin All procedures performed in studies involving human was 80 g/L; and total platelet count was 92×109/L. participants were in accordance with the ethical standards of Thereafter, she received anti-infective for 8 day and IVIG the institutional research committee and with the Helsinki treatment for 2 day. However, she still had a fever and a Declaration (as revised in 2013). Written informed consent cough and then transferred into our hospital. She had a was obtained from the patient. poor physical fitness, and recurrent onychomycosis was present after 2 years. There was a history of repeated oral ulcers and a history of long-term use of Chinese medicine. General characteristics On physical examination, she was conscious with anemic Case 1 (Table 1): a 2-year-old male had right lower limb appearance; palpable beaded lymph nodes were found above mass about 2 months ago and developed recurrent fever the left clavicle with poor mobility, unclear borders and and cough 20 days ago. His mother found a mass sized partial fusion; the neck could move freely; moist rales were 6 cm × 5 cm at the right lower limb about 2 months ago. noted on auscultation; the heart rate was 100 beats/min; The mass was hard and had no redness and no ulcer. The pot belly was observed, the liver was touched 4.5 cm below skin on the tumor gradually became blue and purple, and the ribs, the spleen was 7.5 cm below the ribs with hard then he visited the local hospital but did not improve. texture. Laboratory examination results were shown in Twenty days ago, he developed fever and the highest body Table 1. Chest and abdomen CT showed splenomegaly, and temperature reached 40.3 , accompanied by cough and uneven enhancement of undefined nodules in the spleen; wheezing. He was suspected with tuberculosis on chest CT, pulmonary infection (fungal infection or tuberculosis) ℃ and then HRZE was administered for anti-tuberculotic (Figure 2); findings after lymph node biopsy were consistent treatment without therapeutic efficacy. But the symptoms with those of fungal lymphadenitis (Figure 2). Bone marrow did not improve, skin test with PPD and tuberculosis-related culture and sputum fungus culture showed Marneffe T cell examination showed negative to mycobacterium penicillin. tuberculosis. Then, this patient was transferred into our Case 3 (Table 1): a female girl aged 2 years was admitted department. On physical examination, the patient was due to abdominal distension for 6 months, fever for 15 days, conscious, but malnutritional; multiple enlarged lymph icteric sclera for 7 days, and cough for 4 days. She developed nodes were noted, the neck could move freely, moist rales abdominal distension 6 months ago. But no attention were noted in both lungs on auscultation; the heart rate was was paid to. She had fever 15 days ago with the highest 130 beats/min, pot belly and thin subcutaneous fat were temperature of 39.9 . She was given oral medicine without observed, liver localized 5 cm below ribs with hard texture, improvement. She then developed jaundice 1 week ago, and ℃ and the spleen was not accessible; a mass sized 5~6 cm paroxysmal cough with exacerbated abdominal distension was found near the right ankle; the mass was hard, had no and jaundice 4 days ago. She was admitted in a local tenderness and redness, and the extremities were warm. hospital and treated for 4 days without any improvement. Results of laboratory examination were shown in Table 1. On physical examination, she was conscious with jaundice Enhanced chest CT showed pulmonary tuberculosis with and icteric sclera. No palpable lymph node was found. bloodborne dissemination and fungal infection (Figure 1); The respiratory rate was slightly increased, and moist rales bronchoscopy showed the granulomatous hyperplasia were noted in both lungs on auscultation. Abdomen was which obstructed the opening of right middle trachea with distent. The liver was 6.5 cm below the ribs, the spleen mucosal erosion and necrosis; The low limb CT showed a was 4.5 cm below the ribs with hard texture. CRT was mass at the middle and lower segments of the right fibula, 1–2 s. Laboratory examination was shown in Table 1: IL-6 © Annals of Palliative Medicine. All rights reserved. Ann Palliat Med 2021;10(7):8437-8447 | http://dx.doi.org/10.21037/apm-20-2056 Annals of Palliative Medicine, Vol 10, No 7 July 2021 8439 Table 1 General information of cases 1, 2 and 3 Items Case 1 Case 2 Case 3 Age 2 years 4 years 10 months 2 years Gender Male Female Female Chief complaint Right lower extremity mass for Fever with cough for 14 days Abdominal distension for 2 months with recurrent fever and 6 months, fever for