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Disseminated Cryptococcus neoformans infection involving multiple bones and lung in an immunocompetent patient: a case report



Cryptococcal osteomyelitis is a rare and potentially serious condition, typically encountered in individuals with compromised immune systems. This case underscores the unusual occurrence of disseminated Cryptococcosis in an immunocompetent person, involving multiple bones and lungs, with Cryptococcus neoformans identified as the causative agent.

Case presentation

An Indonesian man, previously in good health, presented with a chief complaint of successive multiple bone pain lasting for more one month, without any prior history of trauma. Additionally, he reported a recent onset of fever. On physical examination, tenderness was observed in the left lateral chest wall and right iliac crest. Laboratory findings indicated mildly elevated inflammatory markers. A computed tomography (CT) scan of the chest revealed an ovoid solid nodule in the right lower lung and multifocal osteolytic lesions in the sternum, ribs, and humeral head. A magnetic resonance imaging (MRI) study of the sacrum showed multiple lesions in the bilateral iliac bone and the lower L4 vertebral body. Confirmation of Cryptococcal osteomyelitis involved a fine-needle biopsy and culture, identifying Cryptococcus neoformans in the aspirate. The patient responded positively to targeted antifungal treatments, leading to a gradual improvement in his condition.


This case emphasizes the need to consider Cryptococcus neoformans osteomyelitis in immunocompetent patients with bone pain. A definitive diagnosis involves a fine-needle biopsy for pathology and culture, and prompt initiation of appropriate antifungal treatment has proven effective in preventing mortality.

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Cryptococcosis stands as a noteworthy global opportunistic infection, predominantly impacting immunocompromised individuals, including patients with human immunodeficiency virus (HIV), organ transplant recipients, and those with malignancies [1,2,3]. However, there are also documented instances of cryptococcal infections occurring in immunocompetent hosts [4, 5]. Cryptococcosis primarily affects the respiratory and central nervous systems (CNS) [2], with bone involvement being rare. Over 95% of cryptococcal infections are caused by Cryptococcus neoformans, while Cryptococcus gattii is responsible for the rest, particularly in immunocompetent hosts [1, 6]. Both thrive in environments with bird droppings, like contaminated soil [7]. Cryptococcus usually gain entry through the respiratory system, causing respiratory complications, and demonstrates a neurotropic inclination by selectively affecting the central nervous system [2]. Bone involvement occurs in less than 10% of disseminated Cryptococcosis cases [1, 8]. This report outlines an uncommon instance of disseminated Cryptococcosis in an immunocompetent individual, affecting multiple bones and lung attributed to Cryptococcus neoformans.

Case presentation

A previously healthy 28-year-old married Indonesian male, employed in the textile industry in Taiwan, presented with one month of progressive bone pain. Initially, he reported posterior neck pain a month ago. About a week before admission, he experienced left-sided chest pain. He sought outpatient care, where Ibuprofen and dexamethasone tablets were administered for three days. Subsequently, he developed discomfort in the right iliac crest region, radiating down his back thigh to the calf. He was later hospitalized due to a one-day fever peaking at 40.6 °C, accompanied by chills. He did not report muscle weakness, numbness, or any urinary or fecal incontinence. Furthermore, he showed no night sweats, cough, or sputum production, and had not experienced trauma or weight loss. The patient had no history of antibiotic or immunosuppressant use, except for a three-day, total 3 mg course of dexamethasone prior to admission. He denied any recent exposure to soil or birds. He had not traveled in the past 3 years. Furthermore, he had no history of smoking or alcohol consumption. Additionally, there were no reported instances of intravenous drug use, blood product transfusions, or casual sexual activity in his medical history.

On physical examination, the patient presented as acutely ill, yet remained awake, alert, and oriented to time, place, and person. His vital signs were as follows: oral temperature 40.6 °C, pulse rate 147 beats/min, respiratory rate 21 breaths/min, and blood pressure 110/79 mmHg. Notably, respiratory, cardiac, and abdominal examinations yielded unremarkable findings. Nonetheless, tenderness was noted in the left lateral chest wall and right iliac crest. No redness or swelling was observed. The straight leg raising test was negative, and motor examination revealed normal strength (5/5 power) in both legs. No palpable lymph nodes or signs of oral candidiasis were observed.

Table 1 displays laboratory findings revealing an elevated erythrocyte sedimentation rate (ESR) of 64 mm/h (reference range 0–15), a slightly increased C-reactive protein (CRP) level of 2.82 mg/dL (reference range < 1). SARS-CoV-2 RNA and Influenza antigen tests were negative. White blood cell count: 8.3^3/µL (reference range 3.5–9.1), 71.6% neutrophils (reference range 39.4–72.6%), 11.7% lymphocytes (reference range 21–51%). Hemoglobin: 12.5 g/dL (reference range 14–17). Elevated alanine aminotransferase (ALT): 66 U/L (reference range 11–42). Alkaline phosphatase (ALP): 71 U/L (reference range 34–104). Bilirubin: 0.4 mg/dL (reference range 0.3–1.0). Glucose: 104 mg/dL (reference range < 140). ANA reactivity: positive at  1:160 (reference range 1:80(-)). Complement C3: 163.4 mg/dL (reference range 87.0–200.0). Complement C4: 46.2 mg/dL (reference range 13.1–50.2). Tumor markers: CA199 8.5 U/mL (reference range  35.0), CEA 1.5 ng/mL (reference range < 5.0 non-smoker), PSA 1.117 ng/mL (reference range  4.0). Urinalysis and blood cultures: negative. Results of the serum biochemistry tests were essentially normal. Assessment for an underlying immunodeficiency was negative for HIV and autoantibodies against interferon-gamma (IFN-γ) or granulocyte-macrophage colony-stimulating factor (GM-CSF). Lumbar puncture (LP) showed clear, colorless cerebrospinal fluid (CSF) with an opening pressure of 65 mmH2O. CSF parameters were normal: cell count < 4/µL (reference range, 0–5), glucose 69 mg/dL (reference range, 40–70), and protein 44.3 mg/dL (reference range, 15–45). Cryptococcus polymerase chain reaction (PCR) was negative. India ink staining was not done. CSF and blood cultures were negative for bacterial or fungal growth. Chest X-ray showed increased lung markings in lower lung fields (Fig. 1). Lumbar spine X-ray ruled out compression fracture. Sacrum X-ray indicated mild narrowing of the L5-S1 disc. Liver echo indicated splenomegaly of unknown cause. Nerve conduction studies (NCS) of the lower limbs were normal. Magnetic resonance imaging (MRI) of the sacrum showed multiple lesions in the bilateral iliac bone and lower L4 vertebral body (Fig. 2). A 99mTc whole body bone scan indicated an increased uptake in the left parietal bone, left lower cervical spine, L2, L4, bilateral SI joint, right knee, left ankle, anterolateral left 1st and 3rd ribs, and posterior left 10th rib (Fig. 3). Furthermore, a chest computed tomography (CT) scan showed a 0.85 cm ovoid solid nodule in the right lower lung and multiple osteolytic bony lesions in the sternum, left 1st and 3rd ribs, and right humeral head (Fig. 4). A CT-guided biopsy confirmed Cryptococcus infection in the L4 vertebral body and right iliac bone. Fine-needle aspiration cytology, stained with Grocott’s-Gomori Methenamine silver (GMS), revealed Cryptococcus. Histopathological analysis confirmed a granuloma consistent with Cryptococcosis (Figs. 5 and 6), and cultures from the aspirate yielded Cryptococcus neoformans at both sites. The patient’s serum Cryptococcal antigen titer of 1:2560 confirmed disseminated Cryptococcosis, suggesting probable involvement in the sternum, left 1st and 3rd ribs, right humeral head, right lower lung, and definitively affecting the L4 spine and both iliac bones. After admission, the patient received IV amoxicillin/clavulanate (1500 mg every 8 h). Persistent fever and bone pain indicated Cryptococcosis, leading to subsequent treatment with IV amphotericin B (0.7 mg/kg/day) and oral flucytosine (100 mg/kg/day in 4 divided doses) for 4 weeks. Upon improvement, the patient was discharged with a one-year prescription for oral fluconazole (400 mg/day). Inflammatory markers, such as ESR and CRP, consistently remained within normal limits, and the patient remained symptom-free post-discharge.

Table 1 Laboratory results
Fig. 1
figure 1

Chest X-ray showing mild increased lung markings in both lower lung fields

Fig. 2
figure 2

Magnetic resonance imaging (MRI) of the sacrum revealing diffuse decreased T1 signals affecting the thoracolumbar spine and bilateral iliac bones, along with multiple T2 hyperintensity lesions showing enhancement in the bilateral iliac bones and lower L4 vertebral body

Fig. 3
figure 3

Tc-99 m whole-body bone scan revealing areas of increased activity in the left parietal bone, left lower cervical spine, L2, L4, bilateral sacroiliac joints, right knee, left ankle, and the anterolateral aspects of the left 1st, 3rd, and posterior left 10th ribs

Fig. 4
figure 4

Chest computed tomography (CT) scan revealing a 0.85 cm ovoid solid nodule in the right lower lung, along with multifocal osteolytic bony lesions observed in the sternum, left 1st, 3rd ribs, and right humeral head

Fig. 5
figure 5

This section reveals necrosis with yeast cells and focal aggregate of epithelioid histiocytes with multinucleated giant cells (arrow), suggesting granulomatous inflammation

Fig. 6
figure 6

The special stains of PAS (upper) and GMS (lower) highlight the yeast cells of cryptococcus (arrows)


Cryptococcosis, a potentially fatal fungal infection, primarily affects immunocompromised individuals worldwide, especially those with HIV or post-solid organ transplantation [1, 2]. Usually gaining entry through the lungs, Cryptococcus frequently results in pneumonia and meningitis [2]. Cryptococcal osteomyelitis is uncommon, typically stemming from a primary pulmonary infection that spreads through the bloodstream [8, 9] or, less commonly, through traumatic inoculation via the skin [10]. The patient experienced one month of widespread bone pain and a new onset of fever, with no evidence of respiratory infection or prior trauma. A CT scan of the chest found a radiopaque nodule in the right middle lung field, challenging to biopsy due to its sub-centimeter size. The spread of infection from the lungs to blood stream and disseminated to the bones is a possible explanation. The individual displayed no identified risk factors for immunocompromise, including but not limited to diabetes (random glucose: 104 mg/L), sarcoidosis, malignancy (CA199: 8.5U/mL; CEA: 1.5ng/mL; PSA: 1.117 ng/mL), solid organ transplant, or prolonged steroid usage. In Kuo et al.‘s investigation, six of 23 patients with disseminated Cryptococcus harbored anti-GM-CSF autoantibodies, and all five with positive culture reports were infected with Cryptococcus gattii [11]. The association between the presence of anti-interferon-γ autoantibodies and the onset of immunodeficiency with intracellular infections has been clearly established [12,13,14,15]. Cryptococcus, typically extracellular, evades the host immune system by forming phagosomes, and preventing phagocytosis through “titan cells” formation [16, 17]. Consequently, our assessment for immunodeficiency related to HIV and the presence of auto-antibodies against IFN-γ or GM-CSF yielded negative results. Despite ANA reactivity (  1:160+), low-titer ANA can occur in subacute/chronic infection. Cryptococcal osteomyelitis, primarily caused by Cryptococcus neoformans, typically affects immunocompromised individuals [18, 19], including those with sarcoidosis, tuberculosis, steroid therapy, or diabetes mellitus [20]. However, it can also occur in immunocompetent individuals [10, 21,22,23]. Apparently, the patient has not disclosed any immune deficiency. Disseminated Cryptococcus neoformans infection involving multiple bones and lungs was diagnosed. It’s important to note that certain immune deficiencies may only become apparent through advanced investigations that are currently beyond our reach. Clinical presentation, bone pain, and osteolytic lesions resembled metastatic malignancy. Definitive diagnosis via fine-needle aspiration biopsy and culture revealed Cryptococcal osteomyelitis. Imaging lacks typical features, but previous reports document lesions mimicking malignancy [24].


In immunocompetent hosts presenting with bone pain and osteolytic lesions, Cryptococcal osteomyelitis should be included in the differential diagnosis. The definite diagnosis should be confirmed through FNAC and fungal culture, with further investigation into immunological assessments recommended.

Data availability

All relevant data are within the paper and its supporting information files.



computed tomography


Magnetic resonance imaging


human immunodeficiency virus


central nervous system


Straight leg raising test


erythrocyte sedimentation rate


C-reactive protein


fine-needle aspiration cytology


antinuclear antibody


carbohydrate antigen 19 − 9


carcinoembryonic antigen


Prostate-Specific Antigen


Interferon gamma


granulocyte-macrophage colony-stimulating factor


Cerebrospinal fluid


polymerase chain reaction


  1. Maziarz EK, Perfect JR, Cryptococcosis. Infect Dis Clin N Am. 2016;30(1):179–206.

    Article  Google Scholar 

  2. Li SS, Mody CH, Cryptococcus. Proc Am Thorac Soc. 2010;7(3):186–96.

    Article  PubMed  Google Scholar 

  3. Zhang Y, Yu YS, Tang ZH, Zang GQ. Cryptococcal osteomyelitis of the scapula and rib in an immunocompetent patient. Med Mycol. 2012;50(7):751–5.

    Article  CAS  PubMed  Google Scholar 

  4. Kwon-Chung KJ, Fraser JA, Doering TL, Wang Z, Janbon G, Idnurm A, et al. Cryptococcus neoformans and Cryptococcus gattii, the etiologic agents of cryptococcosis. Cold Spring Harbor Perspect Med. 2014;4(7):a019760.

    Article  Google Scholar 

  5. Zhao Y, Ye L, Zhao F, Zhang L, Lu Z, Chu T, et al. Cryptococcus neoformans, a global threat to human health. Infect Dis Poverty. 2023;12(1):20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Chen SC, Meyer W, Sorrell TC. Cryptococcus gattii infections. Clin Microbiol Rev. 2014;27(4):980–1024.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Mada PK, Jamil RT, Alam MU, Cryptococcus. StatPearls. Treasure Island (FL) ineligible companies. Disclosure: Radia Jamil declares no relevant financial relationships with ineligible companies. Disclosure: Mohammed Alam declares no relevant financial relationships with ineligible companies.: StatPearls Publishing Copyright © 2024. StatPearls Publishing LLC.; 2024.

  8. Al-Tawfiq JA, Ghandour J. Cryptococcus neoformans abscess and osteomyelitis in an immunocompetent patient with tuberculous lymphadenitis. Infection. 2007;35(5):377–82.

    Article  CAS  PubMed  Google Scholar 

  9. Armonda RA, Fleckenstein JM, Brandvold B, Ondra SL. Cryptococcal skull infection: a case report with review of the literature. Neurosurgery. 1993;32(6):1034–6. discussion 6.

    Article  CAS  PubMed  Google Scholar 

  10. Qadir I, Ali F, Malik UZ, Umer M. Isolated cryptococcal osteomyelitis in an immunocompetent patient. J Infect Developing Ctries. 2011;5(9):669–73.

    Article  Google Scholar 

  11. Kuo PH, Wu UI, Pan YH, Wang JT, Wang YC, Sun HY, et al. Neutralizing anti-granulocyte-macrophage colony-stimulating factor autoantibodies in patients with Central Nervous System and localized cryptococcosis: Longitudinal Follow-Up and Literature Review. Clin Infect Diseases: Official Publication Infect Dis Soc Am. 2022;75(2):278–87.

    Article  Google Scholar 

  12. Roerden M, Döffinger R, Barcenas-Morales G, Forchhammer S, Döbele S, Berg CP. Simultaneous disseminated infections with intracellular pathogens: an intriguing case report of adult-onset immunodeficiency with anti-interferon-gamma autoantibodies. BMC Infect Dis. 2020;20(1):828.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Lin CH, Chi CY, Shih HP, Ding JY, Lo CC, Wang SY, et al. Identification of a major epitope by anti-interferon-γ autoantibodies in patients with mycobacterial disease. Nat Med. 2016;22(9):994–1001.

    Article  CAS  PubMed  Google Scholar 

  14. Chi CY, Chu CC, Liu JP, Lin CH, Ho MW, Lo WJ, et al. Anti-IFN-γ autoantibodies in adults with disseminated nontuberculous mycobacterial infections are associated with HLA-DRB1*16:02 and HLA-DQB1*05:02 and the reactivation of latent varicella-zoster virus infection. Blood. 2013;121(8):1357–66.

    Article  CAS  PubMed  Google Scholar 

  15. Patel SY, Ding L, Brown MR, Lantz L, Gay T, Cohen S et al. Anti-IFN-gamma autoantibodies in disseminated nontuberculous mycobacterial infections. Journal of immunology (Baltimore, Md: 1950). 2005;175(7):4769-76.

  16. Leopold Wager CM, Hole CR, Wozniak KL, Wormley FL. Jr. Cryptococcus and phagocytes: complex interactions that Influence Disease Outcome. Front Microbiol. 2016;7:105.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Zaragoza O, Nielsen K. Titan cells in Cryptococcus neoformans: cells with a giant impact. Curr Opin Microbiol. 2013;16(4):409–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Medaris LA, Ponce B, Hyde Z, Delgado D, Ennis D, Lapidus W, et al. Cryptococcal osteomyelitis: a report of 5 cases and a review of the recent literature. Mycoses. 2016;59(6):334–42.

    Article  PubMed  Google Scholar 

  19. Zhou HX, Lu L, Chu T, Wang T, Cao D, Li F, et al. Skeletal cryptococcosis from 1977 to 2013. Front Microbiol. 2014;5:740.

    PubMed  Google Scholar 

  20. Liu PY. Cryptococcal osteomyelitis: case report and review. Diagn Microbiol Infect Dis. 1998;30(1):33–5.

    Article  CAS  PubMed  Google Scholar 

  21. Dumenigo A, Sen M. Cryptococcal osteomyelitis in an Immunocompetent patient. Cureus. 2022;14(1):e21074.

    PubMed  PubMed Central  Google Scholar 

  22. Zhong Y, Huang Y, Zhang D, Chen Z, Liu Z, Ye Y. Isolated cryptococcal osteomyelitis of the sacrum in an immunocompetent patient: a case report and literature review. BMC Infect Dis. 2023;23(1):116.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Ma JL, Liao L, Wan T, Yang FC. Isolated cryptococcal osteomyelitis of the ulna in an immunocompetent patient: a case report. World J Clin Cases. 2022;10(19):6617–25.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Witte DA, Chen I, Brady J, Ramzy I, Truong LD, Ostrowski ML. Cryptococcal osteomyelitis. Report of a case with aspiration biopsy of a humeral lesion with radiologic features of malignancy. Acta Cytol. 2000;44(5):815–8.

    Article  CAS  PubMed  Google Scholar 

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The authors appreciate Dr. Cheng-Lung Ku and colleagues at Chang Gung University for their assistance in identifying auto-antibodies against IFN-γ or GM-CSF. We also acknowledge Dr. Kun-Tu Yeh for providing the production of pathological images.


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YM Lee designed this study and wrote the manuscript, TC Chen and YM Liu edited the manuscript. KT Yeh contributed to pathological image. All authors read and approved the final manuscript.

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Correspondence to Yang-Ming Lee.

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Lee, YM., Liu, YM. & Chen, TC. Disseminated Cryptococcus neoformans infection involving multiple bones and lung in an immunocompetent patient: a case report. BMC Infect Dis 24, 397 (2024).

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