{"paper_id":"4922bea4-e28b-442c-9a49-1dfeb94c026a","body_text":"A Case of Cutaneous Cryptococcosis and Literature Review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report A Case of Cutaneous Cryptococcosis and Literature Review Shurui Wu, Pei Zhao, Biwen Lin, Xiaoning Zhang, Kun Ye, Chengxin Li, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5159751/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Background When a patient presents with painful skin ulcers accompanied by purulent discharge and there is a possibility of immune deficiency, the potential for opportunistic pathogen infection should be considered. Case Presentation This report presents a case of a skin cryptococcal infection in a 68-year-old female patient who had been on long-term oral ruxolitinib due to myelofibrosis. The skin lesions were characterized by red plaques on the inner side of the right upper arm, accompanied by painful ulcers that had persisted for 9 months. Following an incision and drainage procedure locally, there was continuous purulent exudate that did not heal. Pathological examination indicated diffuse lymphocytic infiltration in the dermis, with a small number of neutrophils, and PAS staining was positive. Cultures of the purulent discharge revealed Cryptococcus neoformans in full view, with positive India ink staining. Serum cryptococcal antigen testing was positive, and after antifungal treatment and daily wound irrigation, the lesions healed. Conclusions This article briefly introduces the diagnosis and treatment process of the patient in this case and further analyzes the possible causes. Our literature review reveals that skin cryptococcosis lesions are typically non-specific, and clinical manifestations alone are insufficient for a definitive diagnosis. It is essential to maintain clinical vigilance and combine tissue pathology and microbiological examinations. Cutaneous cryptococcosis Disseminated fungal infection Immune function suppression Figures Figure 1 Figure 2 Figure 3 Figure 4 1. Introduction Cryptococcus includes over 38 species in fungal taxonomy, of which two are considered potentially pathogenic: Cryptococcus neoformans and Cryptococcus gattii, both of which can cause localized or disseminated cutaneous cryptococcosis [ 1 ] . The common route of entry for Cryptococcus into the human body is via pulmonary inhalation. Once disseminated, approximately 80% of cases may present as cryptococcal meningitis [ 3 ] , while only 5–15% of patients with disseminated cryptococcosis exhibit cutaneous manifestations [ 1 ] . Therefore, cutaneous cryptococcosis is relatively rare. When dermatologists encounter atypical symptoms in patients like the one described in this case, along with a high suspicion of infectious issues, they should consider the possibility of infection by rare pathogens. Notably, the patient reported in this case also has high-risk factors, such as hematologic dysfunction due to bone marrow fibrosis (including anemia and reduced immune cell counts) and long-term oral JAK inhibitors, which should alert physicians to the potential for rare pathogen infections during differential diagnosis. 2. Case Presentation The patient is a 68-year-old female. She has had a painful plaque on the inner side of her right upper arm for over 9 months. Approximately 9 months ago, a red plaque the size of a coin appeared on the inner side of her right arm, accompanied by pain. The rash gradually enlarged, became harder, ulcerated, and formed an ulcer. Four months ago, she visited the Liao Ning Central Hospital, where a skin ultrasound was performed, and considering it to be an \"abscess,\" she underwent incision and drainage. Bacterial cultures were negative, and pathology indicated: purulent inflammation of soft tissue with abscess formation and tissue cell proliferation. She was treated with penicillin infusion for 14 days, but the original ulcer and incision site continued to fail to heal, accompanied by pus discharge. Additionally, six small ulcers appeared at the original rash site, all of which were treated with incision and drainage, but the wounds continued to fail to heal and discharge pus. She received another 19 days of intravenous penicillin infusion. During the course of the illness, the patient denies experiencing fever, abdominal pain, melena, or hematochezia. There is no report of Raynaud's phenomenon, joint pain, photophobia, or hair loss. Mental state, physical strength, appetite, and sleep are normal, with no significant changes in body weight, and bowel and bladder functions are normal. Dermatology examination reveals three ulcers on the inner side of the right upper arm, the largest measuring approximately 3x8.5 cm, and two smaller ones measuring about 0.5x1.0 cm. All three skin lesions show signs of serous bleeding and pink granulation tissue, with yellow purulent fluid exuding between them. Sinus tracts have formed between the three ulcers, and there is a pale edematous ring surrounding them, with patches of pigment deposition observed laterally. Several areas of erosion are noted around the ulcers, covered with brown scabs. No enlargement of cervical or axillary lymph nodes was observed (Fig. 1 A). The patient has a history of hypertension for over 20 years and has been treated with oral medication, with blood pressure well controlled. Bone marrow fibrosis was discovered 16 months ago, and the patient has received blood transfusions three times due to “anemia” caused by the bone marrow fibrosis (specific details not available). The patient has been on long-term oral treatment with ruxolitinib, taking 10 mg in the morning and 5 mg in the evening; 2 mg of azacitidine three times a day; 5 mg of prednisone at noon; and 50 mg of thalidomide at noon. The patient underwent thyroid nodule resection 10 years ago and has been receiving treatment with levothyroxine. The patient was born in Liaoyang County, Liaoning Province, and has lived in this area for a long time, residing about 1 km from a mining area. There is no history of living in epidemic zones, epidemic areas, or areas with polluted water; no history of living in pastoral areas, high fluoride areas, or low iodine areas; no history of contact with chemical substances, radioactive materials, or toxins; no history of drug use; no history of smoking; and no history of alcohol consumption. There is no significant family medical history. Test results report: White blood cell count: 7.89 x 10^9/L; Neutrophils: 0.57 N; CRP: 3.055 mg/dl; Interleukin-6: 6.26 pg/ml; Hemoglobin: 76 g/L; Procalcitonin: 0.111 ng/ml; Alanine aminotransferase: 145 U/L; Aspartate aminotransferase: 74.2 U/L; Erythrocyte sedimentation rate: 104 mm/h; Tuberculosis infection T-cell test (B antigen) 15 SFC; Antinuclear antibodies 1:100 positive; No significant abnormalities found in the autoimmune antibody profile; Hepatitis B surface antigen, hepatitis B core antibody, hepatitis C virus, syphilis-specific antibodies, and human immunodeficiency virus (HIV) were all negative. Fungal and Aspergillus tests negative; Cytomegalovirus (CMV-IgG > 180 U/ml, CMV-IgM 22.4 U/ml). Magnetic resonance imaging of the elbow suggests: extensive diffuse abnormal signals in the right elbow joint cavity and surrounding area, with involvement of bone marrow and surrounding soft tissue, and exudative changes in the surrounding soft tissue. Skin pathology: diffuse infiltration of histiocytes in the dermis, with visible lymphocytes in the surrounding area, local erythrocyte extravasation, and a small number of neutrophils detected (Figs. 2 A-B). PAS staining positive (Fig. 2 C), acid-fast staining negative; spherical fungi observed under microscopy (Figs. 3 A-C). Skin swab (purulent secretion) culture indicates: Cryptococcus neoformans in full view (Fig. 4 A). Ink staining positive (Fig. 4 B). Drug sensitivity testing indicates voriconazole < = 0.12, 5-fluorocytosine 4.0. Further improve chest CT and cranial MRI. Chest CT suggests: bilateral pulmonary infectious lesions, multiple nodules in both lungs, likely benign. Sputum culture indicates: positive for Catamaran bacteria, negative for fungi. Consider pulmonary bacterial infection. Further cranial MRI indicates: suspicious punctate enhancement lesions near the bilateral lateral ventricles and in the right basal ganglia region. Continue with lumbar puncture; routine and biochemical analysis of cerebrospinal fluid showed no abnormalities. Cerebrospinal fluid smear and pathogen second-generation sequencing (NGS) tests showed no abnormalities. Cerebrospinal fluid culture and cryptococcal capsular polysaccharide antigen quantification showed no significant abnormalities, ruling out the possibility of central nervous system infection. Therefore, we diagnose: primary cutaneous cryptococcosis. The patient was treated with 3g of cefoperazone/sulbactam every 12 hours and 400mg of fluconazole daily. We also performed daily washings with hydrogen peroxide solution and sodium chloride injection, assisted with cold compresses using Renovation solution and benzalkonium chloride solution, combined with red light therapy for inflammation reduction. Topical recombinant human acidic fibroblast growth factor was used to promote healing, alongside silver ion antibacterial dressings for protection, ensuring that the wound remained clean and moist. After seven days of continuous wound cleaning, the ulcer on the patient's right upper arm appeared dark yellow, with dark red patches surrounding it, and purulent exudate had decreased compared to before (Fig. 1 B). After two weeks of fluconazole treatment, the ulcer on the right upper arm showed a dark red color with a small amount of thin purulent discharge (Fig. 1 C). We performed surgical debridement. The abscess was washed with hydrogen peroxide and saline, and necrotic tissue was surgically removed. At the same time, we increased the frequency of dressing changes, applied petroleum jelly gauze for drainage and to prevent adhesion, and used chlortetracycline ointment for anti-inflammatory treatment. There was no further purulent exudate observed, and the wound showed significant healing, markedly reduced in size since admission. During this period, pink granulation tissue and a small amount of thin exudate were noted. At the distal two ulcer sites, healing surfaces showed pigment deposition (Fig. 1 D). We continued to apply recombinant human acidic fibroblast growth factor to promote healing and performed wet compresses with benzalkonium chloride and Renovation solution for 20 minutes twice daily, while continuing oral fluconazole at 400mg once daily. Liver and kidney functions were monitored regularly. After six months, follow-up (Fig. 1 E) showed an adjustment to fluconazole 200mg once daily, with discontinuation of treatment after continuing for two months. No new skin lesions were observed, and the existing lesions were healing well. 3. Discussion Cryptococcus neoformans and Cryptococcus gattii are the main pathogenic species of PCC, representing yeast-like fungi widely distributed around the world, existing in bird droppings, soil, fruits, and plants. As a conditional pathogen, Cryptococcus can infect individuals with compromised immune systems as well as those with normal immunity, causing various types of lesions on the skin, which can lead to potential misdiagnoses. The patient in this case suffers from hematopoietic dysfunction due to myelofibrosis and has risk factors such as long-term use of Ruxolitinib; clinical manifestations are non-specific, necessitating high suspicion of conditional pathogens. Ruxolitinib is a selective inhibitor of Janus-related kinases (JAK family), specifically JAK1 and JAK2, and is clinically used for intermediate or high-risk primary myelofibrosis. JAK inhibitors can suppress the host immune response, thus impacting its defense against pathogens [ 2 ] , which can increase the risk of infections. A meta-analysis in the United States regarding infections associated with Ruxolitinib indicated that common infectious complications included herpes zoster (8%), bronchitis (6.1%), and urinary tract infections (6%) [ 4 ] , but did not include cryptococcal infections; another statistical analysis regarding infections in myelofibrosis patients receiving Ruxolitinib only suggested an increased incidence of herpes zoster infections, without reporting an increased risk of fungal infections [ 5 ] . However, another study indicated that cryptococcal infections are not uncommon (9%), and may also lead to tuberculosis (34%) and reactivation of hepatitis B virus (9%) [ 6 ] . Current beliefs suggest that such patients do not require prophylactic antifungal treatment when using JAK inhibitors [ 7 ] ; therefore, in this case, the initial suspicion for the pathogen primarily focused on fungal or mycobacterial infections. The primary skin lesion in this patient was a solitary painful plaque on the upper limb. During treatment at an outside hospital, multiple incisions and drainage procedures were performed. Subsequently, smaller new lesions and ulcers appeared around the original skin lesion, suggesting that this patient may have initially presented with a less common localized cryptococcal infection. It cannot be ruled out that indiscriminate incision and drainage led to the dissemination of the infection. In the future, surgical treatment for such patients may need to be considered only after appropriate systemic antifungal therapy at the right time. Once diagnosed, these patients should be further monitored for the possibility of infection involving other vital organs (such as the central nervous system, lungs, bones, etc.) or for the presence of other infections; reports have indicated the potential for multiple opportunistic infections [ 8 ] . Early diagnosis and treatment are also crucial, as there have been reports of patients presenting with explosive cryptococcal infections that initially manifest as myocardial infarction [ 9 ] . A very small number of patients may die from this type of opportunistic infection [ 10 ] , indicating that the infection can also lead to acute critical conditions. According to a survey in Japan, approximately 85% of patients with disseminated cryptococcosis have an immunodeficient state due to underlying diseases [ 1 ] , immunosuppressive drug treatment, and/or other reasons. This suggests that after diagnosing disseminated cryptococcosis, it is important to promptly analyze the presence of any immunodeficiency factors and further consider whether the underlying disease or factors leading to immunodeficiency require collaboration with other departments for management. Based on existing treatment experiences, when patients develop invasive fungal infections after using ruxolitinib, only a few continue or restart oral ruxolitinib after discontinuation, while most case reports indicate permanent cessation of ruxolitinib [ 11 ] . Therefore, it is necessary to collaborate with the hematology department to adjust the treatment plan for myelofibrosis. The treatment plan for this patient involves long-term oral fluconazole, and given the potential for resistance in cryptococci [ 12 ] , subsequent follow-ups should remain vigilant for the possibility of treatment failure or dissemination of the infection. 4. Management Disseminated cryptococcosis can affect any organ in the body, thus necessitating a thorough clinical evaluation. Our patient's cranial MRI and chest CT scans showed some confusion. However, after screening, the possibilities of central nervous system and pulmonary involvement were ruled out. Following systemic antifungal treatment and daily dressing changes, the patient's clinical symptoms showed significant improvement. The Infectious Diseases Society of America (IDSA) has updated the management guidelines for cryptococcosis, including a classification based on organ involvement. Patients with central nervous system (CNS) disease should be treated with liposomal amphotericin B (AmB) (3–4 mg/kg/day intravenously) or amphotericin B lipid complex (ABLC) (5 mg/kg/day intravenously) combined with flucytosine (100 mg/kg/day in four divided doses) for at least 2 weeks, followed by oral fluconazole (400–800 mg (6–12 mg/kg) per day) for 8 weeks, and then low-dose oral fluconazole (200 to 400 mg/day) for 6 to 12 months. If flucytosine has not been used from the beginning, treatment with liposomal amphotericin B (LFAmB) should be considered for 4 to 6 weeks. Patients with a high fungal burden or those who experience a relapse may be treated with liposomal amphotericin B (6 mg/kg/day). In immunocompetent patients, disseminated non-CNS cryptococcal infections can be treated with oral fluconazole 400 mg for 3–6 months or itraconazole for 6–12 months. The initial treatment approach for immunosuppressed patients is the same, but lifelong maintenance therapy with fluconazole may be required. Primary skin disease can be treated with oral fluconazole or itraconazole [ 13 ] . This case involves a patient with immunosuppression who did not receive liposomal amphotericin or flucytosine during the induction phase and was treated directly with fluconazole (400 mg once daily). After systemic antifungal treatment, the clinical manifestations improved significantly. The clinical manifestations of cutaneous cryptococcosis can vary significantly, especially in patients with immunosuppression. It is essential to maintain a high level of clinical vigilance and to combine histopathological and microbiological examinations. Declarations Consent for publication The patient has given written informed consent for her personal and clinical details along with identifying images to be published in this study. Data availability Some or all data used during the study are available from the corresponding author by request. Competing interests The authors declare no competing interests. Funding This work is supported by the Beijing Natural Science Foundation Project (7244298); Clinical Research Support Project of the General Hospital of the People's Liberation Army(22QNFC076). Author contributions SW collected the data and wrote the manuscript. CS provided the main direction and ideas for the diagnosis of the disease. CL, BL,PZ participated in patient management. XZ and KY provided the corresponding data for organizational pathology diagnosis and pathogen microbiological testing. All authors have read and approved the final manuscript. Acknowledgements We thank the patient for her permission to publish this article and the institutional affiliations for supporting this effort. References Noguchi H, Matsumoto T, Kimura U, et al. Cutaneous Cryptococcosis[J]. Med Mycol J, 2019,60(4):101-107. Samuel C, Cornman H, Kambala A, et al. A Review on the Safety of Using JAK Inhibitors in Dermatology: Clinical and Laboratory Monitoring[J]. Dermatol Ther (Heidelb), 2023,13(3):729-749. 赵俊英,王毓新,张文娟主编. 真菌病诊断与治疗. 人民卫生出版社,2007.03,第192页 Samuel C, Cornman H, Kambala A, et al. A Review on the Safety of Using JAK Inhibitors in Dermatology: Clinical and Laboratory Monitoring[J]. Dermatol Ther (Heidelb), 2023,13(3):729-749. Verstovsek S, Mesa R A, Gotlib J, et al. Long-term treatment with ruxolitinib for patients with myelofibrosis: 5-year update from the randomized, double-blind, placebo-controlled, phase 3 COMFORT-I trial[J]. J Hematol Oncol, 2017,10(1):55. Dioverti M V, Abu S O, Tande A J. Infectious complications in patients on treatment with Ruxolitinib: case report and review of the literature[J]. Infect Dis (Lond), 2018,50(5):381-387. Little J S, Weiss Z F, Hammond S P. Invasive Fungal Infections and Targeted Therapies in Hematological Malignancies[J]. J Fungi (Basel), 2021,7(12). Sayabovorn N, Chongtrakool P, Chayakulkeeree M. Cryptococcal fungemia and Mycobacterium haemophilum cellulitis in a patient receiving ruxolitinib: a case report and literature review[J]. BMC Infect Dis, 2021,21(1):27. Liu J, Mouhayar E, Tarrand J J, et al. Fulminant Cryptococcus neoformans infection with fatal pericardial tamponade in a patient with chronic myelomonocytic leukaemia who was treated with ruxolitinib: Case report and review of fungal pericarditis[J]. Mycoses, 2018,61(4):245-255. Ogai A, Yagi K, Ito F, et al. Fatal Disseminated Tuberculosis and Concurrent Disseminated Cryptococcosis in a Ruxolitinib-treated Patient with Primary Myelofibrosis: A Case Report and Literature Review[J]. Intern Med, 2022,61(8):1271-1278. Chiu C Y, John T M, Matsuo T, et al. Disseminated Histoplasmosis in a Patient with Myelofibrosis on Ruxolitinib: A Case Report and Review of the Literature on Ruxolitinib-Associated Invasive Fungal Infections[J]. J Fungi (Basel), 2024,10(4). Yang C, Bian Z, Blechert O, et al. High Prevalence of HIV-Related Cryptococcosis and Increased Resistance to Fluconazole of the Cryptococcus neoformans Complex in Jiangxi Province, South Central China[J]. Front Cell Infect Microbiol, 2021,11:723251. J. R. Perfect, W. E. Dismukes, F. Dromer, D. L. Goldman,R. John, and J. R. Graybill, “Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the Infectious Diseases Society of America,” Clinical Infectious Diseases, vol. 50, no. 3, pp. 291–322, 2010. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 28 Oct, 2024 Reviews received at journal 28 Oct, 2024 Reviews received at journal 21 Oct, 2024 Reviewers agreed at journal 21 Oct, 2024 Reviewers agreed at journal 17 Oct, 2024 Reviewers invited by journal 15 Oct, 2024 Editor invited by journal 01 Oct, 2024 Editor assigned by journal 29 Sep, 2024 Submission checks completed at journal 29 Sep, 2024 First submitted to journal 26 Sep, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-5159751\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Case Report\",\"associatedPublications\":[],\"authors\":[{\"id\":371526384,\"identity\":\"c6fca109-2b49-4744-8ed0-fe7bf5e9f29d\",\"order_by\":0,\"name\":\"Shurui Wu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Department of Dermatology, First Medical Center, Chinese People's Liberation Army General Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Shurui\",\"middleName\":\"\",\"lastName\":\"Wu\",\"suffix\":\"\"},{\"id\":371526385,\"identity\":\"d19d9d28-c570-4cf5-83fb-224d45571ebb\",\"order_by\":1,\"name\":\"Pei Zhao\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Department of Dermatology, First Medical Center, Chinese People's Liberation Army General Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Pei\",\"middleName\":\"\",\"lastName\":\"Zhao\",\"suffix\":\"\"},{\"id\":371526386,\"identity\":\"781379d3-2dfa-492e-aa17-4258bcd05228\",\"order_by\":2,\"name\":\"Biwen Lin\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Department of Dermatology, First Medical Center, Chinese People's Liberation Army General Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Biwen\",\"middleName\":\"\",\"lastName\":\"Lin\",\"suffix\":\"\"},{\"id\":371526387,\"identity\":\"8dd72ff6-bc95-4613-9200-619f5503f8da\",\"order_by\":3,\"name\":\"Xiaoning Zhang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Department of Dermatology, First Medical Center, Chinese People's Liberation Army General Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Xiaoning\",\"middleName\":\"\",\"lastName\":\"Zhang\",\"suffix\":\"\"},{\"id\":371526388,\"identity\":\"2dbed1d4-916a-48a5-9916-06dd3513ecac\",\"order_by\":4,\"name\":\"Kun Ye\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Department of Dermatology, First Medical Center, Chinese People's Liberation Army General Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Kun\",\"middleName\":\"\",\"lastName\":\"Ye\",\"suffix\":\"\"},{\"id\":371526389,\"identity\":\"9b5eee1f-d90f-42f3-841d-9a45b2ce57c5\",\"order_by\":5,\"name\":\"Chengxin Li\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Department of Dermatology, First Medical Center, Chinese People's Liberation Army General Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Chengxin\",\"middleName\":\"\",\"lastName\":\"Li\",\"suffix\":\"\"},{\"id\":371526390,\"identity\":\"fa4accb8-3747-4d65-9502-5217c9dad710\",\"order_by\":6,\"name\":\"Cuihao Song\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA10lEQVRIiWNgGAWjYBACNvbGhgMJBjZy8uzNBx8kVNQQ1sLHc7jxwIeKNGPDnmPJBg/OHCOsRU4ivfngjDOHExlu5KhJPmxhJsJhPAcbDvO2MScwzshhq0hsYGPgb+9OIOgXoBa2PHaet8duJO6QYZA4c3YDMbbwFDO256XdSDzDxmAgkUtAi0QiSAuQPJBjVpDYxkycFqD3DRIbTuSYMRCnBegwYCAngANZIuHMMR6CfpFvb3/8IcHgPzgqP/6oqJHjb+/FrwUD8JCmfBSMglEwCkYBVgAA6XhTAh3Q9VsAAAAASUVORK5CYII=\",\"orcid\":\"\",\"institution\":\"Department of Dermatology, First Medical Center, Chinese People's Liberation Army General Hospital\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Cuihao\",\"middleName\":\"\",\"lastName\":\"Song\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2024-09-26 15:23:13\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-5159751/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-5159751/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":69850739,\"identity\":\"396e2620-4087-4925-9883-1ff9fd7a01e6\",\"added_by\":\"auto\",\"created_at\":\"2024-11-25 23:30:31\",\"extension\":\"png\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":4748906,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e(A) Upon admission, the patient had three ulcers on the inner side of the right upper arm, all displaying oozing blood and pink granulation tissue, with yellow pus exuding between them. A sinus tract formed among the three ulcers, surrounded by pale edematous rings, with pigmented patches observed laterally. Several eroded areas were noted around the ulcers. (B) Seven days after continuous debridement, the color of the right upper arm ulcer appeared dark yellow, with surrounding dark red patches, and purulent exudate had decreased compared to earlier. (C) Treatment with fluconazole for 14 days + dressing changes + surgical debridement. (D) Before discharge (E) Follow-up two months after discharge\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"Figure1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5159751/v1/b65930f570c4f7929cfe3930.png\"},{\"id\":69850736,\"identity\":\"0eae506e-8323-40b3-b6e6-60d04af02f6e\",\"added_by\":\"auto\",\"created_at\":\"2024-11-25 23:30:31\",\"extension\":\"png\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":1203122,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e(A) Biopsy specimen has no epidermis, dermis and subcutaneous diffuse histiocytic infiltrate with abundant presence and necrosis. (Hematoxylin-eosin staining, original magnification X10) (B) Multiple yeast-like spores share a mucinous capsule, forming an oval, translucent region in the section containing a large number of small granular spores. (Hematoxylin-eosin staining, original magnification X100) (C) PAS staining showed a large number of spores, some of which were arranged in a linear manner and had buds.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"Figure2.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5159751/v1/2aa16fb8965e3cfcaa01395b.png\"},{\"id\":69850737,\"identity\":\"bd9f6dd1-4360-4fee-9789-e15135639dd4\",\"added_by\":\"auto\",\"created_at\":\"2024-11-25 23:30:31\",\"extension\":\"png\",\"order_by\":3,\"title\":\"Figure 3\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":424251,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e(A) Skin swab-Gram-1000X, (B) Skin swab-ink stain-400X, (C) Skin swab-fluorescent stain-400X stain-400X\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"Figure3.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5159751/v1/7455c1508efb06a34a4f122d.png\"},{\"id\":69851005,\"identity\":\"9f976627-1abb-48ab-8463-05ee8842b0d4\",\"added_by\":\"auto\",\"created_at\":\"2024-11-25 23:38:31\",\"extension\":\"png\",\"order_by\":4,\"title\":\"Figure 4\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":585459,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e(A) 35° normal culture for 72 h - Chinese blue, (B) 35° normal culture for 72 h - ink staining\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"Figure4.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5159751/v1/f3937e064d88b22a7436069e.png\"},{\"id\":69851089,\"identity\":\"2faa6923-169d-4663-9dbb-0db5f54dba99\",\"added_by\":\"auto\",\"created_at\":\"2024-11-25 23:46:35\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":10568992,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5159751/v1/bc702267-6e99-40bc-91ac-d83536bb4d3b.pdf\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"A Case of Cutaneous Cryptococcosis and Literature Review\",\"fulltext\":[{\"header\":\"1. Introduction\",\"content\":\"\\u003cp\\u003eCryptococcus includes over 38 species in fungal taxonomy, of which two are considered potentially pathogenic: Cryptococcus neoformans and Cryptococcus gattii, both of which can cause localized or disseminated cutaneous cryptococcosis\\u003csup\\u003e[\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e]\\u003c/sup\\u003e. The common route of entry for Cryptococcus into the human body is via pulmonary inhalation. Once disseminated, approximately 80% of cases may present as cryptococcal meningitis\\u003csup\\u003e[\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e]\\u003c/sup\\u003e, while only 5\\u0026ndash;15% of patients with disseminated cryptococcosis exhibit cutaneous manifestations\\u003csup\\u003e[\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e]\\u003c/sup\\u003e. Therefore, cutaneous cryptococcosis is relatively rare. When dermatologists encounter atypical symptoms in patients like the one described in this case, along with a high suspicion of infectious issues, they should consider the possibility of infection by rare pathogens. Notably, the patient reported in this case also has high-risk factors, such as hematologic dysfunction due to bone marrow fibrosis (including anemia and reduced immune cell counts) and long-term oral JAK inhibitors, which should alert physicians to the potential for rare pathogen infections during differential diagnosis.\\u003c/p\\u003e\"},{\"header\":\"2. Case Presentation\",\"content\":\"\\u003cp\\u003eThe patient is a 68-year-old female. She has had a painful plaque on the inner side of her right upper arm for over 9 months. Approximately 9 months ago, a red plaque the size of a coin appeared on the inner side of her right arm, accompanied by pain. The rash gradually enlarged, became harder, ulcerated, and formed an ulcer. Four months ago, she visited the Liao Ning Central Hospital, where a skin ultrasound was performed, and considering it to be an \\\"abscess,\\\" she underwent incision and drainage. Bacterial cultures were negative, and pathology indicated: purulent inflammation of soft tissue with abscess formation and tissue cell proliferation. She was treated with penicillin infusion for 14 days, but the original ulcer and incision site continued to fail to heal, accompanied by pus discharge. Additionally, six small ulcers appeared at the original rash site, all of which were treated with incision and drainage, but the wounds continued to fail to heal and discharge pus. She received another 19 days of intravenous penicillin infusion.\\u003c/p\\u003e \\u003cp\\u003eDuring the course of the illness, the patient denies experiencing fever, abdominal pain, melena, or hematochezia. There is no report of Raynaud's phenomenon, joint pain, photophobia, or hair loss. Mental state, physical strength, appetite, and sleep are normal, with no significant changes in body weight, and bowel and bladder functions are normal. Dermatology examination reveals three ulcers on the inner side of the right upper arm, the largest measuring approximately 3x8.5 cm, and two smaller ones measuring about 0.5x1.0 cm. All three skin lesions show signs of serous bleeding and pink granulation tissue, with yellow purulent fluid exuding between them. Sinus tracts have formed between the three ulcers, and there is a pale edematous ring surrounding them, with patches of pigment deposition observed laterally. Several areas of erosion are noted around the ulcers, covered with brown scabs. No enlargement of cervical or axillary lymph nodes was observed (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003eA).\\u003c/p\\u003e \\u003cp\\u003eThe patient has a history of hypertension for over 20 years and has been treated with oral medication, with blood pressure well controlled. Bone marrow fibrosis was discovered 16 months ago, and the patient has received blood transfusions three times due to \\u0026ldquo;anemia\\u0026rdquo; caused by the bone marrow fibrosis (specific details not available). The patient has been on long-term oral treatment with ruxolitinib, taking 10 mg in the morning and 5 mg in the evening; 2 mg of azacitidine three times a day; 5 mg of prednisone at noon; and 50 mg of thalidomide at noon. The patient underwent thyroid nodule resection 10 years ago and has been receiving treatment with levothyroxine. The patient was born in Liaoyang County, Liaoning Province, and has lived in this area for a long time, residing about 1 km from a mining area. There is no history of living in epidemic zones, epidemic areas, or areas with polluted water; no history of living in pastoral areas, high fluoride areas, or low iodine areas; no history of contact with chemical substances, radioactive materials, or toxins; no history of drug use; no history of smoking; and no history of alcohol consumption. There is no significant family medical history.\\u003c/p\\u003e \\u003cp\\u003eTest results report: White blood cell count: 7.89 x 10^9/L; Neutrophils: 0.57 N; CRP: 3.055 mg/dl; Interleukin-6: 6.26 pg/ml; Hemoglobin: 76 g/L; Procalcitonin: 0.111 ng/ml; Alanine aminotransferase: 145 U/L; Aspartate aminotransferase: 74.2 U/L; Erythrocyte sedimentation rate: 104 mm/h; Tuberculosis infection T-cell test (B antigen) 15 SFC; Antinuclear antibodies 1:100 positive; No significant abnormalities found in the autoimmune antibody profile; Hepatitis B surface antigen, hepatitis B core antibody, hepatitis C virus, syphilis-specific antibodies, and human immunodeficiency virus (HIV) were all negative. Fungal and Aspergillus tests negative; Cytomegalovirus (CMV-IgG\\u0026thinsp;\\u0026gt;\\u0026thinsp;180 U/ml, CMV-IgM 22.4 U/ml).\\u003c/p\\u003e \\u003cp\\u003eMagnetic resonance imaging of the elbow suggests: extensive diffuse abnormal signals in the right elbow joint cavity and surrounding area, with involvement of bone marrow and surrounding soft tissue, and exudative changes in the surrounding soft tissue. Skin pathology: diffuse infiltration of histiocytes in the dermis, with visible lymphocytes in the surrounding area, local erythrocyte extravasation, and a small number of neutrophils detected (Figs.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003eA-B). PAS staining positive (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003eC), acid-fast staining negative; spherical fungi observed under microscopy (Figs.\\u0026nbsp;\\u003cspan refid=\\\"Fig3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003eA-C). Skin swab (purulent secretion) culture indicates: Cryptococcus neoformans in full view (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig4\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003eA). Ink staining positive (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig4\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003eB). Drug sensitivity testing indicates voriconazole\\u0026thinsp;\\u0026lt;\\u0026thinsp;=\\u0026thinsp;0.12, 5-fluorocytosine 4.0.\\u003c/p\\u003e \\u003cp\\u003eFurther improve chest CT and cranial MRI. Chest CT suggests: bilateral pulmonary infectious lesions, multiple nodules in both lungs, likely benign. Sputum culture indicates: positive for Catamaran bacteria, negative for fungi. Consider pulmonary bacterial infection. Further cranial MRI indicates: suspicious punctate enhancement lesions near the bilateral lateral ventricles and in the right basal ganglia region. Continue with lumbar puncture; routine and biochemical analysis of cerebrospinal fluid showed no abnormalities. Cerebrospinal fluid smear and pathogen second-generation sequencing (NGS) tests showed no abnormalities. Cerebrospinal fluid culture and cryptococcal capsular polysaccharide antigen quantification showed no significant abnormalities, ruling out the possibility of central nervous system infection. Therefore, we diagnose: primary cutaneous cryptococcosis.\\u003c/p\\u003e \\u003cp\\u003eThe patient was treated with 3g of cefoperazone/sulbactam every 12 hours and 400mg of fluconazole daily. We also performed daily washings with hydrogen peroxide solution and sodium chloride injection, assisted with cold compresses using Renovation solution and benzalkonium chloride solution, combined with red light therapy for inflammation reduction. Topical recombinant human acidic fibroblast growth factor was used to promote healing, alongside silver ion antibacterial dressings for protection, ensuring that the wound remained clean and moist. After seven days of continuous wound cleaning, the ulcer on the patient's right upper arm appeared dark yellow, with dark red patches surrounding it, and purulent exudate had decreased compared to before (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003eB). After two weeks of fluconazole treatment, the ulcer on the right upper arm showed a dark red color with a small amount of thin purulent discharge (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003eC). We performed surgical debridement. The abscess was washed with hydrogen peroxide and saline, and necrotic tissue was surgically removed. At the same time, we increased the frequency of dressing changes, applied petroleum jelly gauze for drainage and to prevent adhesion, and used chlortetracycline ointment for anti-inflammatory treatment. There was no further purulent exudate observed, and the wound showed significant healing, markedly reduced in size since admission. During this period, pink granulation tissue and a small amount of thin exudate were noted. At the distal two ulcer sites, healing surfaces showed pigment deposition (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003eD). We continued to apply recombinant human acidic fibroblast growth factor to promote healing and performed wet compresses with benzalkonium chloride and Renovation solution for 20 minutes twice daily, while continuing oral fluconazole at 400mg once daily. Liver and kidney functions were monitored regularly. After six months, follow-up (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003eE) showed an adjustment to fluconazole 200mg once daily, with discontinuation of treatment after continuing for two months. No new skin lesions were observed, and the existing lesions were healing well.\\u003c/p\\u003e\"},{\"header\":\"3. Discussion\",\"content\":\"\\u003cp\\u003eCryptococcus neoformans and Cryptococcus gattii are the main pathogenic species of PCC, representing yeast-like fungi widely distributed around the world, existing in bird droppings, soil, fruits, and plants. As a conditional pathogen, Cryptococcus can infect individuals with compromised immune systems as well as those with normal immunity, causing various types of lesions on the skin, which can lead to potential misdiagnoses. The patient in this case suffers from hematopoietic dysfunction due to myelofibrosis and has risk factors such as long-term use of Ruxolitinib; clinical manifestations are non-specific, necessitating high suspicion of conditional pathogens. Ruxolitinib is a selective inhibitor of Janus-related kinases (JAK family), specifically JAK1 and JAK2, and is clinically used for intermediate or high-risk primary myelofibrosis. JAK inhibitors can suppress the host immune response, thus impacting its defense against pathogens\\u003csup\\u003e[\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e]\\u003c/sup\\u003e, which can increase the risk of infections. A meta-analysis in the United States regarding infections associated with Ruxolitinib indicated that common infectious complications included herpes zoster (8%), bronchitis (6.1%), and urinary tract infections (6%)\\u003csup\\u003e[\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e]\\u003c/sup\\u003e, but did not include cryptococcal infections; another statistical analysis regarding infections in myelofibrosis patients receiving Ruxolitinib only suggested an increased incidence of herpes zoster infections, without reporting an increased risk of fungal infections\\u003csup\\u003e[\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e]\\u003c/sup\\u003e. However, another study indicated that cryptococcal infections are not uncommon (9%), and may also lead to tuberculosis (34%) and reactivation of hepatitis B virus (9%)\\u003csup\\u003e[\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e]\\u003c/sup\\u003e. Current beliefs suggest that such patients do not require prophylactic antifungal treatment when using JAK inhibitors\\u003csup\\u003e[\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e]\\u003c/sup\\u003e; therefore, in this case, the initial suspicion for the pathogen primarily focused on fungal or mycobacterial infections.\\u003c/p\\u003e \\u003cp\\u003eThe primary skin lesion in this patient was a solitary painful plaque on the upper limb. During treatment at an outside hospital, multiple incisions and drainage procedures were performed. Subsequently, smaller new lesions and ulcers appeared around the original skin lesion, suggesting that this patient may have initially presented with a less common localized cryptococcal infection. It cannot be ruled out that indiscriminate incision and drainage led to the dissemination of the infection. In the future, surgical treatment for such patients may need to be considered only after appropriate systemic antifungal therapy at the right time. Once diagnosed, these patients should be further monitored for the possibility of infection involving other vital organs (such as the central nervous system, lungs, bones, etc.) or for the presence of other infections; reports have indicated the potential for multiple opportunistic infections\\u003csup\\u003e[\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e]\\u003c/sup\\u003e. Early diagnosis and treatment are also crucial, as there have been reports of patients presenting with explosive cryptococcal infections that initially manifest as myocardial infarction\\u003csup\\u003e[\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e]\\u003c/sup\\u003e. A very small number of patients may die from this type of opportunistic infection\\u003csup\\u003e[\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e]\\u003c/sup\\u003e, indicating that the infection can also lead to acute critical conditions.\\u003c/p\\u003e \\u003cp\\u003eAccording to a survey in Japan, approximately 85% of patients with disseminated cryptococcosis have an immunodeficient state due to underlying diseases\\u003csup\\u003e[\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e]\\u003c/sup\\u003e, immunosuppressive drug treatment, and/or other reasons. This suggests that after diagnosing disseminated cryptococcosis, it is important to promptly analyze the presence of any immunodeficiency factors and further consider whether the underlying disease or factors leading to immunodeficiency require collaboration with other departments for management. Based on existing treatment experiences, when patients develop invasive fungal infections after using ruxolitinib, only a few continue or restart oral ruxolitinib after discontinuation, while most case reports indicate permanent cessation of ruxolitinib\\u003csup\\u003e[\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e]\\u003c/sup\\u003e. Therefore, it is necessary to collaborate with the hematology department to adjust the treatment plan for myelofibrosis. The treatment plan for this patient involves long-term oral fluconazole, and given the potential for resistance in cryptococci\\u003csup\\u003e[\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e]\\u003c/sup\\u003e, subsequent follow-ups should remain vigilant for the possibility of treatment failure or dissemination of the infection.\\u003c/p\\u003e\"},{\"header\":\"4. Management\",\"content\":\"\\u003cp\\u003eDisseminated cryptococcosis can affect any organ in the body, thus necessitating a thorough clinical evaluation. Our patient's cranial MRI and chest CT scans showed some confusion. However, after screening, the possibilities of central nervous system and pulmonary involvement were ruled out. Following systemic antifungal treatment and daily dressing changes, the patient's clinical symptoms showed significant improvement.\\u003c/p\\u003e \\u003cp\\u003eThe Infectious Diseases Society of America (IDSA) has updated the management guidelines for cryptococcosis, including a classification based on organ involvement. Patients with central nervous system (CNS) disease should be treated with liposomal amphotericin B (AmB) (3\\u0026ndash;4 mg/kg/day intravenously) or amphotericin B lipid complex (ABLC) (5 mg/kg/day intravenously) combined with flucytosine (100 mg/kg/day in four divided doses) for at least 2 weeks, followed by oral fluconazole (400\\u0026ndash;800 mg (6\\u0026ndash;12 mg/kg) per day) for 8 weeks, and then low-dose oral fluconazole (200 to 400 mg/day) for 6 to 12 months. If flucytosine has not been used from the beginning, treatment with liposomal amphotericin B (LFAmB) should be considered for 4 to 6 weeks. Patients with a high fungal burden or those who experience a relapse may be treated with liposomal amphotericin B (6 mg/kg/day).\\u003c/p\\u003e \\u003cp\\u003eIn immunocompetent patients, disseminated non-CNS cryptococcal infections can be treated with oral fluconazole 400 mg for 3\\u0026ndash;6 months or itraconazole for 6\\u0026ndash;12 months. The initial treatment approach for immunosuppressed patients is the same, but lifelong maintenance therapy with fluconazole may be required. Primary skin disease can be treated with oral fluconazole or itraconazole\\u003csup\\u003e[\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e]\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eThis case involves a patient with immunosuppression who did not receive liposomal amphotericin or flucytosine during the induction phase and was treated directly with fluconazole (400 mg once daily). After systemic antifungal treatment, the clinical manifestations improved significantly. The clinical manifestations of cutaneous cryptococcosis can vary significantly, especially in patients with immunosuppression. It is essential to maintain a high level of clinical vigilance and to combine histopathological and microbiological examinations.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eConsent for publication\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe patient has given written informed consent for her personal and clinical details along with identifying images to be published in this study.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eData availability\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eSome or all data used during the study are available from the corresponding author by request.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCompeting interests\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe authors declare no competing interests.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFunding\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis work is supported by the Beijing Natural Science Foundation Project (7244298); Clinical Research Support Project of the General Hospital of the People\\u0026apos;s Liberation Army(22QNFC076).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAuthor contributions\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eSW collected the data and wrote the manuscript. CS provided the main direction and ideas for the diagnosis of the disease. CL, BL,PZ participated in patient management. XZ and KY provided the corresponding data for organizational pathology diagnosis and pathogen microbiological testing. All authors have read and approved the final manuscript.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAcknowledgements\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eWe thank the patient for her permission to publish this article and the institutional affiliations for supporting this effort.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\n\\u003cli\\u003eNoguchi H, Matsumoto T, Kimura U, et al. Cutaneous Cryptococcosis[J]. Med Mycol J, 2019,60(4):101-107.\\u003c/li\\u003e\\n\\u003cli\\u003eSamuel C, Cornman H, Kambala A, et al. A Review on the Safety of Using JAK Inhibitors in Dermatology: Clinical and Laboratory Monitoring[J]. Dermatol Ther (Heidelb), 2023,13(3):729-749.\\u003c/li\\u003e\\n\\u003cli\\u003e赵俊英,王毓新,张文娟主编. 真菌病诊断与治疗. 人民卫生出版社,2007.03,第192页\\u003c/li\\u003e\\n\\u003cli\\u003eSamuel C, Cornman H, Kambala A, et al. A Review on the Safety of Using JAK Inhibitors in Dermatology: Clinical and Laboratory Monitoring[J]. Dermatol Ther (Heidelb), 2023,13(3):729-749.\\u003c/li\\u003e\\n\\u003cli\\u003eVerstovsek S, Mesa R A, Gotlib J, et al. Long-term treatment with ruxolitinib for patients with myelofibrosis: 5-year update from the randomized, double-blind, placebo-controlled, phase 3 COMFORT-I trial[J]. J Hematol Oncol, 2017,10(1):55.\\u003c/li\\u003e\\n\\u003cli\\u003eDioverti M V, Abu S O, Tande A J. Infectious complications in patients on treatment with Ruxolitinib: case report and review of the literature[J]. Infect Dis (Lond), 2018,50(5):381-387.\\u003c/li\\u003e\\n\\u003cli\\u003eLittle J S, Weiss Z F, Hammond S P. Invasive Fungal Infections and Targeted Therapies in Hematological Malignancies[J]. J Fungi (Basel), 2021,7(12).\\u003c/li\\u003e\\n\\u003cli\\u003eSayabovorn N, Chongtrakool P, Chayakulkeeree M. Cryptococcal fungemia and Mycobacterium haemophilum cellulitis in a patient receiving ruxolitinib: a case report and literature review[J]. BMC Infect Dis, 2021,21(1):27.\\u003c/li\\u003e\\n\\u003cli\\u003eLiu J, Mouhayar E, Tarrand J J, et al. Fulminant Cryptococcus neoformans infection with fatal pericardial tamponade in a patient with chronic myelomonocytic leukaemia who was treated with ruxolitinib: Case report and review of fungal pericarditis[J]. Mycoses, 2018,61(4):245-255.\\u003c/li\\u003e\\n\\u003cli\\u003eOgai A, Yagi K, Ito F, et al. Fatal Disseminated Tuberculosis and Concurrent Disseminated Cryptococcosis in a Ruxolitinib-treated Patient with Primary Myelofibrosis: A Case Report and Literature Review[J]. Intern Med, 2022,61(8):1271-1278.\\u003c/li\\u003e\\n\\u003cli\\u003eChiu C Y, John T M, Matsuo T, et al. Disseminated Histoplasmosis in a Patient with Myelofibrosis on Ruxolitinib: A Case Report and Review of the Literature on Ruxolitinib-Associated Invasive Fungal Infections[J]. J Fungi (Basel), 2024,10(4).\\u003c/li\\u003e\\n\\u003cli\\u003eYang C, Bian Z, Blechert O, et al. High Prevalence of HIV-Related Cryptococcosis and Increased Resistance to Fluconazole of the Cryptococcus neoformans Complex in Jiangxi Province, South Central China[J]. Front Cell Infect Microbiol, 2021,11:723251.\\u003c/li\\u003e\\n\\u003cli\\u003eJ. R. Perfect, W. E. Dismukes, F. Dromer, D. L. Goldman,R. John, and J. R. Graybill, \\u0026ldquo;Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the Infectious Diseases Society of America,\\u0026rdquo; Clinical Infectious Diseases, vol. 50, no. 3, pp. 291\\u0026ndash;322, 2010.\\u003c/li\\u003e\\n\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":false,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":true,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"bmc-infectious-diseases\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"infd\",\"sideBox\":\"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)\",\"snPcode\":\"\",\"submissionUrl\":\"https://www.editorialmanager.com/infd\",\"title\":\"BMC Infectious Diseases\",\"twitterHandle\":\"#bmcinfectdis\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"BMC Series\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Cutaneous cryptococcosis, Disseminated fungal infection, Immune function suppression\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-5159751/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-5159751/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003eBackground\\u003c/strong\\u003e When a patient presents with painful skin ulcers accompanied by purulent discharge and there is a possibility of immune deficiency, the potential for opportunistic pathogen infection should be considered.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCase Presentation\\u003c/strong\\u003e This report presents a case of a skin cryptococcal infection in a 68-year-old female patient who had been on long-term oral ruxolitinib due to myelofibrosis. The skin lesions were characterized by red plaques on the inner side of the right upper arm, accompanied by painful ulcers that had persisted for 9 months. Following an incision and drainage procedure locally, there was continuous purulent exudate that did not heal. Pathological examination indicated diffuse lymphocytic infiltration in the dermis, with a small number of neutrophils, and PAS staining was positive. Cultures of the purulent discharge revealed Cryptococcus neoformans in full view, with positive India ink staining. Serum cryptococcal antigen testing was positive, and after antifungal treatment and daily wound irrigation, the lesions healed.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConclusions\\u003c/strong\\u003e This article briefly introduces the diagnosis and treatment process of the patient in this case and further analyzes the possible causes. Our literature review reveals that skin cryptococcosis lesions are typically non-specific, and clinical manifestations alone are insufficient for a definitive diagnosis. It is essential to maintain clinical vigilance and combine tissue pathology and microbiological examinations.\\u003c/p\\u003e\",\"manuscriptTitle\":\"A Case of Cutaneous Cryptococcosis and Literature Review\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2024-11-25 23:30:26\",\"doi\":\"10.21203/rs.3.rs-5159751/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0},{\"type\":\"decision\",\"content\":\"Revision requested\",\"date\":\"2024-10-29T03:48:09+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2024-10-28T14:41:36+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2024-10-21T20:42:04+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"184371265190425876921435051296957139091\",\"date\":\"2024-10-21T16:39:36+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"287802528267744160134987512752205158481\",\"date\":\"2024-10-17T19:22:11+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewersInvited\",\"content\":\"\",\"date\":\"2024-10-15T14:39:37+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvited\",\"content\":\"\",\"date\":\"2024-10-01T08:05:22+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorAssigned\",\"content\":\"\",\"date\":\"2024-09-30T02:39:41+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"checksComplete\",\"content\":\"\",\"date\":\"2024-09-30T02:39:25+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"submitted\",\"content\":\"BMC Infectious Diseases\",\"date\":\"2024-09-26T15:12:37+00:00\",\"index\":\"\",\"fulltext\":\"\"}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"bmc-infectious-diseases\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"infd\",\"sideBox\":\"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)\",\"snPcode\":\"\",\"submissionUrl\":\"https://www.editorialmanager.com/infd\",\"title\":\"BMC Infectious Diseases\",\"twitterHandle\":\"#bmcinfectdis\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"BMC Series\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"72e18f7f-082f-4e39-8058-ab47f1671231\",\"owner\":[],\"postedDate\":\"November 25th, 2024\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"under-review\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2024-11-25T23:30:26+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2024-11-25 23:30:26\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-5159751\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-5159751\",\"identity\":\"rs-5159751\",\"version\":[\"v1\"]},\"buildId\":\"qtupq5eGEP_6zYnWcrvyt\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}