Sequential Phialemoniopsis curvata and Botryosphaeria dothidea infections over three years in bilateral lower limbs of a rheumatoid arthritis patient: a case-based review

Abstract

Background

Rheumatoid arthritis (RA) patients are at increased risk of opportunistic infections due to immune dysregulation and immunosuppressive therapies.

Methods

A retrospective study describes sequential cutaneous infections caused by Phialemoniopsis curvata and Botryosphaeria dothidea. Mycological examination includes direct microscopy, mycology culture and slide culture of the isolate. Biopsy of the lesion was sent for histopathology and periodic acid-Schiff staining. The PCR product was directly sequenced using both the ITS1 primer and ITS4 primer. Isolate was further identified by scanning electronic microscopy. A literature review was conducted via PubMed and Scopus using keywords related to P. curvata and B. dothidea infections. Clinical, histopathological, and microbiological data from the patient’s case were analyzed, including fungal culture, microscopy, and molecular identification.

Results

The 58-year-old RA patient presented with sequential cutaneous infections caused by Phialemoniopsis curvata and Botryosphaeria dothidea with long-term glucocorticoids and methotrexate, which was confirmed by histopathology, mycology study, PCR sequencing and scanning electronic microscopy. Literature review identified 29 cases, with hematologic involvement and high mortality (25%) in P. curvata infections.

Conclusions

Immunosuppression is the primary risk factor for infections by environmental fungi like P. curvata and B. dothidea. Hematogenous dissemination correlates with poor outcomes, emphasizing the need for early diagnosis and antifungal therapy. Clinicians should maintain high vigilance for atypical fungal pathogens in RA patients on immunosuppressants.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12879-026-12737-5.

Background

Rheumatoid arthritis (RA) is an autoimmune chronic inflammatory joint disease characterized by autoantibodies against immunoglobulin G and citrullinated proteins (i.e., anti-citrullinated protein antibodies). Inadequate treatment can lead to cumulative joint damage and irreversible disability [1]. The prevalence of RA varies widely worldwide, ranging from 0.25% to 1% [2].

Treatment outcomes for RA have improved dramatically due to a dramatic shift in treatment patterns over the past 30 years. From the oldest glucocorticosteroids to the basic drug, methotrexate, and then to a variety of biological agents, clinicians have a variety of options in the treatment of RA. While these immunosuppressive agents have effectively blocked some inflammatory pathways involved in RA pathogenesis, leading to reduced disease activity or remission, they also elevate the risk of infections, particularly fungal infections. The use of glucocorticosteroids, for instance, increases the risk of serious infections by 2-4-fold in a dose-dependent manner [3, 4]. Herein, we describe a case of sequential bilateral lower limb infections caused by distinct dematiaceous environmental fungi in a RA patient under immunosuppressive therapy. Additionally, we present a literature review concerning infections caused by these two environmental fungi.

Methods

Mycological study When pressing the lesions with a lancet, there was purulent discharge. Direct microscope examination by calcofluor white preparation of pyogenic fluid, and incubation on Sabouraud dextrose agar (SDA) inoculated with pyogenic fluid at 25 ℃ for seven days. Slide culture was inoculated on potato dextrose agar at 25 ℃.

Scanning electron microscopy Colonies were fixed with glutaraldehyde, dehydrated and gold coated. Samples were examined and photographed using an environmental SEM (Philips XL30 ESEM, FEI Philips Electroscan, Peabody, MA, U.S.A.) [5].

Molecular testing For DNA extraction, hyphae from a 48-h culture were harvested by filtration, suspended in distilled water in 2-ml Eppendorf tubes. Genomic DNA was extracted using Ezup Fungus Genomic DNA Extraction Kit (Shanghai Sangon BioTech Company, China) according to the manufacturer’s protocol. The universal fungal primer pair was used for amplification: internal transcribed spacer (ITS)1 (5’-TCCGTAGGTGAACCTGCGG-3’) and ITS4 (5’-TCCTCCGCTTATTGATATG-3’). The primers were synthesized by Shanghai Sangon BioTech Company, China. The PCR assay was performed using 1 µl of the test DNA sample in a total reaction volume of 25 µl. The PCR master mix consisted of 12.5 µl of nuclease-free water, 1 µl stock of each primer (10 mM), 9.5 µl of ddH₂O. Thirty-five cycles of amplification were performed in a BioRad MyCycler thermocycler after initial denaturation of DNA at 95 ℃ for 5 min. Each cycle consisted of a denaturation step at 94℃ for 30 s, an annealing step at 57℃ for 30 s, and an extension step at 72℃ for 1.5 min, with a final extension at 72℃ for 10 min following the last cycle. Following amplification, an approximately 528-bp amplicon was detected. DNA sequencing of the PCR product was done at the Shanghai Sangon Biological Engineering Technology Service Company on ABI PRISM 3730DNA sequence, using BigDye terminator v3.1 according to the manufacturer’s protocols [6]. Informed consent to participate was obtained from the participant in the study.

A search in PubMed and Scopus was performed on 7 July 2025, using the keywords “Phialemonium curvatum” OR “Phialemoniopsis curvata” OR “Phialemoniopsis obovatum” OR “Botryosphaeria dothidea” AND “human infection”, including only English language publications. A total of 39 articles showed up; of which, 21 were excluded because they were non-case reviews or involved pathogenesis. The final search ended up with a total of 18 articles. Data extraction or review was performed independently by two authors (X.J.X. and Z.H.L.). Parameters regarding clinical manifestations and treatment outcomes were recorded. For the data analysis, IBM SPSS Statistics V25 has been used.

Results

A 58-year-old woman visited the dermatology clinic with a 4-month history of painful rashes on her left lower extremity in April 2021. She was a farmer and developed rheumatoid arthritis 17 years ago. The patient denied the history of trauma and claimed that she has been receiving glucocorticosteroids therapy in the early stage and is currently taking oral methotrexate (7.5 mg/week). Physical examination revealed swelling, extensive necrotizing inflammatory plaques, and nodules on the left lower extremity (Fig. 1A). When pressing the lesions with a lancet, there was purulent discharge. B-ultrasound showed hypoechoic area under the skin of the left leg, revealing to be inflammatory. The results of blood routine test were normal. Abnormal laboratory tests revealed the following: C-reactive protein 40.9 mg/l (normal, 0.0-10.0 mg/l), erythrocyte sedimentation rate 90 mm/h (normal, 0–20 mm/h), fibrinogen 6.69 g/l (normal, 2–4 g/l), D-Dimer 1.64 mg/l (normal, 0.00-0.55 mg/l), rheumatoid factor 510 U/ml (normal, 0.0–20.0 U/ml), IgG 8.48 g/l (normal, 8.60–17.40 g/l), total cholesterol 7.78 mmol/l (normal, 3.10–5.69 mmol/l), high density lipoprotein 2.04 mmol/l (normal, 1.03–1.05 mmol/l), low density lipoprotein 5.52 mmol/l (normal, 1.55–3.36 mmol/l). In addition, a serum test for human immunodeficiency virus and tuberculosis specific cellular immune response were negative.

Fig. 1.

A Clinical presentation of the left lower extremity at the first infection. B Periodic acid Schiff stain highlighting the fungal hyphae at the first infection (×200). C Periodic acid Schiff stain highlighting the fungal hyphae at the first infection (×400)

Direct microscope examination by calcofluor white preparation of purulent secretion revealed septate fungal hyphae, and histopathological examination of tissue biopsy with hematoxylin-eosin staining revealed hyperkeratosis, mass inflammatory cell infiltration in derma including lymphocytes, epithelioid cells, neutrophil, multinucleated giant cells, peripheral capillaries and collagen hyperplasia. Periodic acid-Schiff staining showed numerous septate hyphae within multinucleated giant cells (Fig. 1B and C).

After 7 days of incubation on SDA inoculated with purulent specimen at 25℃, white, moist and flat colonies grew (Fig. 2A). Subculture onto SDA incubated at 25℃ for 9 days demonstrated the characteristic appearance of a mold, the colonies filled the plate with a diameter of 9 centimeters and were white, woolly centrally, with pale yellow margins. Microscopically, vegetative hyphae and conidia were hyaline, accumulation of hyaline conidia was observed at the apex of long phialides, and most of them were allantoid or sickle shaped (Fig. 2B). Scanning electron microscopy (SEM) images revealed adelophialides (reduced phialides that are not delimited from subtending intercalary hyphal cells by a basal septum), ellipsoidal conidia and spider web like structure beyongd light microscopy (Fig. 2C). Acremonium falciforme and Phialemonium curvatum both produce hyaline, slender phialides and similar conidial morphology, which can lead to misidentification without molecular confirmation. According to these morphological characteristics, we initially identified the strain as A. falciforme. The partial sequence of the 18 S ribosomal RNA gene and 28 S ribosomal RNA gene, the complete sequence of ITS 1, 5.8 S ribosomal RNA gene and ITS 2 of the isolates, which was deposited in GenBank under accession number PV163796 (553 bp), was completely identical to that of Phialemoniopsis curvata strain DM11 (GenBank accession no. KF032658). Based on the history and laboratory results, a diagnosis of primary cutaneous P. curvata infection was made. The patient was treated with itraconazole 400 mg/day for 3 months, followed by 200 mg/day for another 1 month, resulting in the resolution of the skin lesions.

Fig. 2.

A The morphology of P. curvata cultured on Sabouraud’s dextrose agar at 25℃ for 5 days at the first infection. B Slide culture of P. curvata on potato dextrose agar at 25℃on day 5 (Lactic acid cotton blue staining × 400). C Reduced phialides ellipsoidal conidia and spider web like structure (Scanning electron microscopy, ×10000)

However, three years later (January 2024), she returned with similar rashes on her right lower extremity. Dermatological examination revealed slightly raised erythema (Fig. 3A). Whole blood flow cytometry analysis revealed that 12 cytokines were in the normal ranges. Additionally, there was a significant reduction in the counts of lymphocytes (CD45+), T lymphocytes (CD3+), suppressor/cytotoxic T cells (CD8+), helper T cells (CD4+), and B lymphocytes (CD19+). The respective cell counts were as follows: total lymphocytes, 800 cells/mm³ (reference range: 1200–3700 cells/mm³); T lymphocytes, 462 cells/mm³ (690–2540 cells/mm³); cytotoxic T cells, 147 cells/mm³ (190–1140 cells/mm³); helper T cells, 267 cells/mm³ (410–1440 cells/mm³); and B lymphocytes, 58 cells/mm³ (90–560 cells/mm³). Plasma concentrations of methotrexate remained within normal limits beyond 72 h. Direct microscopy, histopathology (Fig. 3 BC), and fungal culture confirmed another cutaneous fungal infection, this time caused by Botryosphaeria dothidea (Fig. 4A-B, GenBank PQ721759). The patient was again treated with itraconazole, and at the 8-month follow-up, the erythema had resolved.

Fig. 3.

A Clinical presentation of the right lower extremity at the second infection. B Periodic acid Schiff stain highlighting the fungal hyphae at the second infection (×200). C Periodic acid Schiff stain highlighting the fungal hyphae at the second infection (×400)

Fig. 4.

A The morphology of B. dothidea cultured on Sabouraud’s dextrose agar at 25℃for 5 days at the second infection. B Slide culture of B. dothidea on potato dextrose agar at 25℃ on day 5 (× 400)

In the literature search, 28 cases with P. curvata or B. dothidea infections were identified. Demographics, underlying disease, baseline drug record, pathogen, organ involvement, treatment and outcomes have been recorded for all patients. The mean age of patients was 49.29 years old (SD ± 25.50), with a male predominance of approximately 3:1. Among the 28 cases, 21 had clearly recorded underlying diseases, 5 had unknown status, and 2 had no underlying diseases. Kidney diseases (8 cases) and tumors (7 cases, primarily hematologic tumors) were the two most prevalent types of underlying conditions. Other conditions included diabetes and heart disease. Fourteen cases had documented medical records, among which ten were on concomitant treatment with immunosuppressive drugs, including steroids, chemotherapy, azathioprine, methotrexate, etc. Twenty-four cases were associated with Phialemoniopsis curvata or Phialemonium curvatum, and four cases with B. dothidea, frequently involving the hematologic system (n = 9), ocular sites (n = 5), cardiac system (n = 4), among others. Twenty-six cases received antifungal therapy, with the majority (n = 14) treated with multiple antifungal agents. Amphotericin B or liposomal amphotericin B served as the preferred initial therapy (n = 14). Of the 29 reported cases in the literature, 17 achieved cure or improvement, while 7 died. The 29 identified case reports (including our case) are shown in Table 1 without gene sequencing [7–24].

Table 1.

Reported cases of P. spp or B. dothidea infection in patients

Number of cases	Authors, y	Age(y)/Sex	Underlying Disease	Therapy at Presentation	Pathogen	Organ Involvement	Treatment	Outcome
1	King D. et al. (1993) [7]	50/F	Renal transplant	prednisone, azathioprine, and cyclosporine; unknown dose	Pa.spp	Left foot	Surgical excision	Recurrence after 2 months; Resolution after an additional surgery
2	King D. et al. (1993) [7]	5/F	Renal transplant	Cyclosporine A, azathioprine, and prednisone; unknown dose	Pa. obovatum	Peritoneum	Amphotericin B 11days; ketoconazole 4 days; flucytosine 9 days; fluconazole; unknown dose	Improvement; no recurrence
3	Guarro J. et al. (1999) [8]	41/M	Acute lymphocytic leukemia	Chemotherapy; unknown dose	Pa. spp	Blood	Amphotericin B (1 mg/kg of body weight daily); the dose was increased to 1.5 mg/kg 22 days later	Death
4	Guarro J. et al. (1999) [8]	37/M	Hodgkin’s disease	Autologous stem cell transplant	Exophiala jeanselmei and Pa. spp.	Blood	Itraconazole (200–400 mg daily)	Resolution at the 6-month follow-up
5	Heins-Vaccari EM. et al. (2001) [9]	30/M	Bone marrow transplant	Busulfan and melphalan; cyclosporin A and Methotrexate; unknown dose	Pa. spp.	Right ankle	Liposomalamphotericin B (3 mg/kg/day); ketoconazole (600 mg/ day); surgical debridement	Resolution at the 12-month follow-up
6	Proia LA. et al. (2004) [10]	35/M	Chronic renal failure	Prednisone (5 mg/ day) and cyclosporine for 10 months	Pa. curvatum	Blood, right eye	Amphotericin B (1.5 mg/kg per day); vitrectomy	Death
7	Proia LA. et al. (2004) [10]	66/M	Long-term hemodialysis	Unknown	Pa. curvatum	Blood	Amphotericin B deoxycholate (1.5 mg/kg per day); intravenous fluconazole (800 mg loading dose, then 400 mg/day)	Death
8	Proia LA. et al. (2004) [10]	70/F	Long-term hemodialysis	Unknown	Pa. spp.	Unknown	Amphotericin B deoxycholate (1 mg/kg per day)	Death
9	Proia LA. et al. (2004) [10]	77/M	Type II diabetes mellitus and chronic renal failure	Hemodialysis	Pa. spp.	Unknown	amphotericin B deoxycholate (1 mg/kg per day) and oral voriconazole (2 loading doses of 400 mg, then 200 mg every 12 h)	Unknown
10	Strahilevitz J. (2005) [11]	84/M	Aortic stenosis, hypertension, chronic renal failure	Unknown	Pa. curvatum	Heart	Amphotericin B	Death
11	Strahilevitz J. (2005) [11]	55/M	Unknown	Unknown	Pa. curvatum	Heart	Amphotericin B (1.5 mg/kg q.d.) for 3 weeks, followed by voriconazole (400 mg q.d.)	Improvement
12	Strahilevitz J. (2005) [11]	71/M	Aortic valve replacement; coronary artery bypass grafting	Unknown	Pa. curvatum	Heart	Amphotericin B; voriconazol-e	Recovery
13	Weinberger M. et al. (2006) [12]	70/M	Type II diabetes mellitus and systemic hypertensi-on	Unknown	Pa. curvatum	Right eye	Intravitreous injections of amphotericin B	Resolution at the 12-month follow-up
14	Osherov A. (2006) [13]	84/M	Aortic valve replacement; hypertensive༛chronic renal failure	Unknown	Pa. curvatum	Heart	Amphotericin B	Death
15	Dan M. et al. (2006) [14]	64/M	Type II diabetes mellitus; hypertension; ischemic heart disease; Osteoarthr-itis	Intraarticular injection of longacting methylprednisolo-ne acetate	Pa. curvatum	Right knee	Unknown	Unknown
16	Rivero M. et al. (2009) [15]	46/M	Alcohol abuse	Unknown	Pa. spp.	Blood	fluconazole (400 mg/day IV); voriconazole;	Improvement
17	Persy B. et al. (2011) [16]	54/F	T-cell non-Hodgkin lymphoma	Allogeneous peripheral blood stem cell transplantation; cyclosporin A	Pa. curvatum	Blood	Voriconazole and fluconazole; amphotericine B and caspofungin	Death
18	Freda R. et al. (2011) [17]	84/M	Cataract	Cataract surgery	Pa. curvatum	Cornea of right eye	Intravitreal injection of Amphotericin B	Failure (enucleation)
19	Zou Y. et al. (2014) [18]	42/M	None	None	Pa. curvatum	Nervous centralis	Intravenous voriconazole; fluconazole and Amphotericin B; fluconazole	Resolution at the 12-month follow-up
20	Noguchi H. et al. (2017) [19]	82/M	Chronic heart failure and hemiparesi-s	Unknown	Bb. dothidea	Nail	Topical efinaconazole for 7 months	Resolution at the 3-month follow-up
21	Roszkowska AM. et al. (2021) [20]	54/F	Unknown	Unknown	Pa. curvatum	Right eye	1% voriconazole and 0.02% polyhexamethylene biguanide	Improvement
22	Tang M. et al. (2022) [21]	38/M	Unknown	Intraocular injections of ceftazidime, vancomycin, dexamethasone, and fluconazole	Pc. curvata	Left eye	Voriconazole injection, Intravenous injection of fluconazole and 1% VRC eye drop;	Recovery
23	Xie HT. et al. (2024) [22]	29/M	None	Unknown	Bb. dothidea	Left eye	Injection-of 0.1% voriconazole; conjunctival pedicle graft surgery	Improvement
24	Sharma S. et al. (2024) [23]	72/M	Unknown	Unknown	Bb. dothidea	Left eye	Voriconazole 1% injection	Recovery
25	Sharma S. et al. (2024) [23]	5/M	Unknown	Unknown	Bb. dothidea	Eye	Voriconazole 1% injection	Failure
26	Özen S. (2024) [24]	17/F	Alveolar rhabdomyosarcoma	Chemotherapy	Pa. curvatum	Blood	Caspofungin; voriconazole	Recovery
27	Özen S. (2024) [24]	3/M	Ependymoma	Chemotherapy	Pa. curvatum	Blood	Intravenous voriconazole; oral voriconazole	Recovery
28	Özen S. (2024) [24]	15/F	Hodgkin’s lymphoma	Chemotherapy	Pa. curvatum	Blood	liposomal amphotericin B	Recovery
29	Our case	58/F	Rheumatoid arthritis	Glucocorticoid, methtrexate	Pa. Curvatum, Bb. dothidea	lower extremity	Itraconazole	Recovery

^a: Phialemonium; ^b: Botryosphaeria; ^c: Phialemoniopsis

Discussion

We described a female RA patient, previously managed with glucocorticosteroids therapy and chronic methotrexate treatment, who developed recurrent cutaneous black fungi infection. The patient’s prolonged immunosuppressive regimen for RA likely resulted in impaired pathogen response [25]. Consistent with her recurrent infections, lymphocyte subset analysis revealed CD⁴⁺ T-cell lymphopenia (267 cells/µL), confirming therapeutically induced immunosuppression. The therapeutic efficacy of glucocorticosteroids in RA is robustly established for controlling disease activity and delaying joint structural damage. However, these benefits must be weighed against well-documented adverse effects including hyperglycaemia, osteoporosis, cataracts, opportunistic infections, and cardiovascular complications [26]. Glucocorticosteroids exert their therapeutic effects through broad inhibition of immune cell activity, thereby increasing infection susceptibility. While this risk demonstrates dose dependency, clinically relevant increases persist even at daily doses < 5 mg prednisone equivalent. Observational studies consistently confirm these associations, with infection risk correlating with glucocorticosteroids dose magnitude and treatment duration [27]. Methotrexate (MTX), an antifolate antimetabolite, inhibits DNA synthesis, repair, and cellular replication. It exerts both anti-inflammatory and immunomodulatory effects. MTX’s favorable therapeutic index has established it as a first-line disease-modifying antirheumatic drug (DMARD), constituting standard therapy in rheumatology practice across diverse healthcare systems [28–31]. MTX provides therapeutic benefit to a substantial proportion of RA) patients but carries significant toxicity risks. Major adverse effects include gastrointestinal disturbances, hepatotoxicity, pneumonitis, hematologic abnormalities, opportunistic infections, nephrotoxicity, and dermatologic manifestations. Clinical evidence confirms increased susceptibility among MTX-treated RA patients, typically presenting as bacterial infections, herpes zoster reactivation, and other opportunistic pathogens [32].

Fungi, ubiquitous eukaryotic microorganisms, colonize diverse environmental niches including soil, water, plant debris, animal excreta, and other organic substrates [33]. Dematiaceous fungi, a taxonomically diverse group of melanized filamentous fungi, are commonly isolated from soil and decaying vegetation. Characterized by melanin pigments within their cell walls, these fungi typically display pigmentation ranging from light brown to black. Currently, this group comprises over 150 species distributed across 70 genera [34]. Dematiaceous fungi are known to cause a range of skin and subcutaneous infections, primarily including PHM and chromoblastomycosis (CBM). Histologically, PHM is distinguished by the presence of both yeast and hyphae in tissue samples, whereas chromoblastomycosis is identified by medlar bodies, also referred to as sclerotic or muriform cells [35]. The clinical manifestations of PHM vary from superficial cutaneous infections to more severe deep or disseminated infections, with the presentation often influenced by the patient’s immune status. Notably, most reported cases of subcutaneous PHM occur in immunocompromised individuals, such as those with autoimmune diseases or post-transplant patients [36].

Phialemoniopsis curvata was formerly known as Phialemonium curvatum. Phialemonium species are widely distributed in the environment, having been isolated from air, soil, industrial water, and sewage [37]. Although well established as a true dematiaceous fungus, having melanin on its cell wall, pigmentation of hyphae and spores are not always apparent as such. It is characterized by moist colonies with short adelophialides lacking basal septa and long slender phialides with basal septa (as seen in Acremonium species), with neither having conspicuous collarettes and with both producing conidia aggregate in slimy heads [38] The genus Phialemonium has been considered to be intermediate between the hyaline Acremonium and the pigmented Phialophora. Regarding clinical identification, the Phialemonium strain is often mistaken for Acremonium species [12, 18], this case also encountered this situation. The genus Phialemonium once included 3 species: P. curvatum, P. obovatum, and P. dimorphosporum - but P. dimorphosporum was later synonymized with P. curvatum [8]. Based on a multilocus sequence analysis of the ITS regions, the D1/D2 domains of the 28 S rRNA (D1/D2), actin (ACT) and β-tubulin genes, Haybrig Perdomo et al. reclassified Phialemonium curvatum as a member of a new genus and assigning it the name Phialemoniopsis curvata [39]. Interestingly, SEM showed the hyphae and conidia of this strain are wrapped in filaments like spider webs, we speculate that this may be a special substance secreted by P. curvatum, which need to be estimated in future studies.

The human infections caused by Phialemoniopsis curvata (with Phialemonium curvatum in the literature reclassified as Phialemoniopsis curvata) are rare, there are only a few documented reports of invasive disease caused by Phialemoniopsis species, which are almost exclusively in immunocompromised patients [9, 10, 16]. The identification of the form-species level or form-genus level is usually difficult, hence the incidence rate of infection due to Phialemoniopsis species could be underestimated [16]. Phialemoniopsis is similar with Acremonium not only in morphology, but also in the ability of adhere to plastic materials and foreign bodies, hence, both fungi are the common cause of catheter infection [40]. This would explain the endovascular nature of the infections in most cases, which are often associated with endocarditis and positive blood cultures [16]. In this case, the route of infection remains unknown. However, long-term immunosuppressive therapy compromised the patient’s immune function, as evidenced by lymphocyte subset analysis, thereby increasing the risk of environmental fungal infection.

Similarly, the environmental dematiaceous fungus B. dothidea is a recognized phytopathogen causing leaf spot, stem canker, stem warts, and fruit rot in multiple economically vital crops [41]. B. dothidea belongs to the family Botryosphaeriaceae, order Botryosphaeriales, class Dothideomycetes, phylum Ascomycota. They primarily reside on woody plants as saprobes [42]. This fungus rarely causes human infections, though it can occasionally lead to keratitis. The primary risk factors for ocular infection in humans involve trauma with vegetative matter. Exposure typically occurs during outdoor occupational activities, such as farming, or during recreational activities in vegetated areas [23]. The Botryosphaeriaceae is a family of morphologically diverse fungi primarily characterized by large, ovoid to oblong, typically aseptate hyaline ascospores [43]. However, B. dothidea-the predominant species within this family-exhibits poor sporulation on standard culture media [23], presenting significant challenges for its identification.

Chromoblastomycosis (CBM) is primarily caused by traumatic implantation during agricultural activities and predominantly affects immunocompetent individuals. In contrast, risk factors for phaeohyphomycosis (PHM) include not only trauma but also immune compromise, such as malnutrition, malignancies, and renal transplantation. Consequently, PHM primarily occurs in immunosuppressed hosts [44–46]. Furthermore, some patients with PHM lack these recognized risk factors and exhibit no detectable immune compromise. Recent advances in the study of human genetics and immunodeficiencies have significantly enhanced our understanding of antifungal immunity. Notably, mutations affecting caspase activation and recruitment domains (CARDs), particularly homozygous mutations in CARD9, represent the most prominent findings. Mutations in the CARD9 gene can lead to impaired cytokine production by immune cells upon stimulation by various fungal ligands, defective recruitment of neutrophils to the site of infection, and dysregulation of interleukin-17 (IL-17)-mediated immune responses. CARD9 deficiency may therefore be implicated in the pathogenesis of PHM in these patients [44].

PHMs range from superficial to deep tissue involvement, including central nervous system phaeohyphomycosis (PHM), disseminated PHM, pulmonary PHM, localized deep PHM, subcutaneous PHM, phaeohyphomycotic keratitis, and superficial infections [34, 35, 47, 48]. CNS PHM is associated with the highest mortality rate, followed by disseminated and pulmonary PHM, respectively [44].

These dematiaceous fungi infect diverse hosts and cause a spectrum of syndromes in organisms with varying susceptibilities. Phialemoniopsis species, for instance, are predominantly associated with disseminated infections and catheter-associated peritoneal dialysis [49, 50]. Among the 28 cases in our literature review, 24 patients infected with P. curvata, 20 had significant underlying diseases, primarily renal transplantation and hematologic malignancies. Immunosuppressive agents or chemotherapy were common therapeutic regimens for these patients. The hematologic system was the most frequently involved site, with a mortality rate as high as 25% (6 of 24 patients) despite most patients initially receiving amphotericin B therapy. All four cases of B. dothidea infection manifested as superficial infections. This limited invasiveness may be attributable to the organism’s inherent virulence factors and specific ecological adaptations within etiological niches.

Melanin, a ubiquitous component of the cell wall in dematiaceous fungi, is considered a key virulence factor. Its pathogenic role, demonstrated across multiple organisms, involves scavenging free radicals and conferring protection against oxidative stress induced by immune effector cells, such as phagocyte-derived reactive oxygen species [49, 51]. Additionally, melanin may contribute to diminished antifungal efficacy, particularly against agents such as amphotericin B and caspofungin [49].

Our study limitation is a rare case study in rheumatoid arthritis and literature review, which need more case studies.

Conclusions

The use of immunosuppressive agents represents the primary risk factor for infections caused by environmental fungi. Patients with hematogenous dissemination exhibit poor prognoses, particularly those infected with P. curvata. Heightened clinical vigilance for rare infections in immunosuppressed patients, coupled with prompt fungal diagnosis, is critical to ensure effective therapeutic intervention. P. curvata and B. dothidea both environmental fungi- cannot reliably rely solely on morphological characteristics for species identification. Molecular techniques represent an effective approach for the accurate identification of such fungi.

Supplementary Information

Below is the link to the electronic supplementary material.

Abbreviations

RA

Rheumatoid arthritis

SDA

Sabouraud dextrose agar

SEM

Scanning electron microscopy

PHM

Phaeohyphomycosis

MTX

Methotrexate

DMARD

Disease-modifying antirheumatic drug

ITS

Internal transcribed spacer

CBM

Chromoblastomycosis

CARDs

Caspase activation and recruitment domains

Author contributions

Xiujiao was responsible for preparing and drafting the manuscript. Zehu Liu provided revision of the manuscript. Each author made substantial contributions to the design of the work, acquisition, and analysis and drafted the work. The authors read and approved the final manuscript.

Funding

This work was supported by Hangzhou Health Science and Technology Plan, China (grant no. Z2024015) and The Construction Fund of Key Medical Disciplines of Hangzhou (2025HZGF07).

Data availability

The datasets used during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

The study was approved by the Medical Ethics Committee at the Hangzhou Third People’s Hospital (protocol code: 2025KA190). All methods in this study were conducted in accordance with relevant guidelines and regulations, including the Helsinki Declaration. Clinical trial number: not applicable.

Consent for publication

I confirm that the patient has given informed written consent to the publication of their personal or clinical details and any identifiable images in this study.

Competing interests

The authors declare no competing interests.