| Abstract|| |
Phaeohyphomycosis is a heterogeneous group of opportunistic infections caused by dematiaceous molds, which are distributed worldwide as plant pathogens but rarely cause human diseases. However, due to the growing populations of immunocompromised patients, these fungi are frequently recognized as important human pathogens. We are reporting this very rare, unique case for the first time from Islamabad, Pakistan, describing the association of visceral Phaeohyphomycosis caused by the opportunistic fungus Alternaria alternata, affecting the left kidney, with the immunocompromised state in a young incidentally detected patient with insulin-dependent type I diabetes. The case was diagnosed on the basis of a high index of clinical suspicion, microbial cultures, microscopy, imaging studies and endourological procedures. The patient did not respond well to the highly sensitive Amphotericin B, resulting in loss of the kidney. Therefore, we suggest that clinicians involved in treating immunocompromised patients should have a high degree of clinical suspicion for such opportunistic pathogens to allow timely initiation of the correct diagnostic and therapeutic work-up.
|How to cite this article:|
Raza H, Khan R U, Anwar K, Muhammad K. Visceral phaeohyphomycosis caused by Alternaria alternata offering a diagnostic as well as a therapeutic challenge. Saudi J Kidney Dis Transpl 2015;26:339-43
|How to cite this URL:|
Raza H, Khan R U, Anwar K, Muhammad K. Visceral phaeohyphomycosis caused by Alternaria alternata offering a diagnostic as well as a therapeutic challenge. Saudi J Kidney Dis Transpl [serial online] 2015 [cited 2021 May 18];26:339-43. Available from: https://www.sjkdt.org/text.asp?2015/26/2/339/152503
| Introduction|| |
Phaeohyphomycosis is a heterogeneous group of opportunistic infections caused by dematiaceous molds, which are distributed worldwide as plant pathogens, but rarely cause human diseases.  However, because of the growing population of immunocompromised patients, including those suffering from diabetes mellitus, malignancies, acquired immunodeficiency syndrome and solid organ transplant recipients, these fungi are increasingly recognized as important human pathogens. , We recently encountered a very rare case of visceral Phaeohyphomycosis caused by the opportunistic fungus Alternaria alternata involving the left kidney of the patient. Our case is unique because the incidentally diagnosed young insulin-dependent type-1 diabetic patient gave us a diagnostic as well as a therapeutic challenge and ultimately resulted in loss of the diseased kidney. Therefore, clinicians involved in treating immunocompromised patients should have a high degree of clinical suspicion for such opportunistic pathogens to allow timely initiation of correct diagnostic and therapeutic work-up. ,,
| Case Report|| |
A 21-year-old male, non-smoker, security guard by profession, was admitted to the Department of Urology for management of pain in the left lumbar region associated with dysuria for the last one year, which gradually worsened since the last five months. The pain was of gradual onset, mild to moderate in intensity, intermittent, dull aching in nature, radiating to the groin and associated with dysuria, but with no history of hematuria. The patient visited several general practitioners but got only temporary symptomatic relief with the prescribed medications. Systemic enquiry was unremarkable. The patient's past medical, surgical, family and medication history was insignificant, with no history of any known allergy. He denied any history of addiction and, socio-economically, belonged to the lower class. On clinical examination at the time of admission, the patient was ill looking, of average build, having normal vitals and unremarkable systemic examination except left lumbar region tenderness with positive renal punch. Initial investigations revealed normal blood counts, erythrocyte sedimentation rate, renal and liver function tests, serum electrolytes, random blood sugar and urine analysis. Hepatitis B and C serology were negative. Ultrasound (USG) of the kidneys, ureters and bladder (KUB) showed obstruction at the left pelvi-ureteric junction (PUJ), causing dilatation of the pelvi-calyceal system. Intravenous urogram (IVU) showed left PUJ obstruction with delayed excretion of contrast while the right kidney was normal. Renal isotope scan was performed, which showed 35% function in the left kidney in association with significant outflow obstruction at the PUJ along with 65% function of the right kidney. The patient was started on broad-spectrum antibiotics, analgesics and supportive treatment. Left pyeloplasty was performed the following day and the patient remained stable for two days with adequate urine output and serosanginous drain fluid of about 150-200 mL/24 h. Unfortunately, on the third post-operative day, he developed severe pain in the left lumbar region. This pain was associated with a significantly increased amount of drain fluid (around 1.5-3 L/24 h) and intermittent urinary retention. The USG of the KUB region was repeated and showed left hydronephrosis with dilatation of the pelvi-calcyeal system and perirenal fluid collection measuring 4.0 cm × 1.3 cm. There were also debrinous echoes in the pelvi-calyceal system and urinary bladder. In view of the above findings, it was decided to proceed for cystoscopy and bladder wash. On cystoscopic examination, the urinary bladder was full of whitish debris that raised the suspicion of fungal infection. A urinary bladder wash was performed and samples were sent for microscopy as well as culture and sensitivity tests.
Diagnosis of visceral Phaeohyphomycosis caused by Alternaria alternata was established by the consultant microbiologist based on a Sabouraud agar culture on which the organisms appeared grayish black and woolly in texture. Microscopic analysis showed the presence of large (10-25 μm), medium brown conidia with a club-like shape and both transverse as well as longitudinal septations with a short beak. Meanwhile, the patient developed deranged renal function and suspected perirenal urine leakage, which was confirmed with drain fluid creatinine level of 6 mg/dL.
The patient was seen by the nephrology team and treatment with amphortericin-B on standard dose (0.6 mg/kg body weight) was started, in consultation with the microbiologist. Diagnostic work-up was initiated to look for any immunocompromised status that predisposed this patient for fungal infection. The laboratory tests revealed high blood sugar readings ranging from 300-400 mg/dL, with a glycosylated hemoglobin (HbA1C) level of 8.5%. The patient was not receiving steroids or immunosuppressive therapy and his human immunodeficiency virus serology was negative.
The patient was diagnosed as having type-1 insulin-dependent diabetes mellitus (IDDM) and was put on regular insulin. Furthermore, he developed a discharging sinus at the site of the operation, with persistent urinary leakage.
Cystoureteroscopy was repeated, which showed a huge dilated pelvis with hydronephrosis and debris in the pelvis. During the procedure, a DJ stent was placed to relieve the obstruction to some extent. Meanwhile, treatment was continued and the patient went home for festival holidays. Upon return, his clinical condition had deteriorated and he had developed high-grade fever with persistent discharge from the operated site. The USG of KUB was repeated which showed dilated left collecting system full of debrinous echoes. One hundred and twenty-five milliliters of debrinous fluid was seen at the lower pole of the left kidney in the peri-nephric area suggestive of left pyonephrosis with fluid collection in the left peri-renal area. The isotope renal scan was also repeated, which showed right kidney function of 68.5%, while the left kidney function was 31.5%, with hydronephrosis and reduced tracer uptake. In view of these findings, it was decided to proceed with left renal exploration. Per-operatively, extensive fibrosis of the peri-nephric area was found along with grossly dilated left kidney with evident necrosis and containing 500-600 mL of thick pus. The left renal pelvis and the lower pole was almost sloughed off [Figure 1]. Therefore, left radical nephrectomy was performed after discussion with the concerned teams. Post-operatively, the patient remained stable, became afebrile and achieved good glycemic control. Urine culture was repeated and was negative for fungal growth. Amphotericin-B was given for a total of 90 days with frequent monitoring for side-effects and management accordingly. He was discharged from the hospital in a hemodynamically stable and improved condition after six weeks of stay. At discharge, his renal function and urine analysis were normal with negative bacterial and fungal cultures. The patient is on regular follow-up with the nephrology and urology departments.
| Discussion|| |
Fungal infections of the kidney usually occur in immunocompromised hosts, caused by opportunistic pathogens. Candidiasis, aspergillosis, blastomycosis, histoplasmosis, coccidioidomycosis and cryptococcosis are the usual infections of the urinary tract causing cystitis, pyelonephritis, fungal bezoars (fungal balls) and disseminated systemic infections, some times. ,,,,, In this case, we are reporting a very rare opportunistic human pathogen, Alternaria, which represents the genus of dematiaceous ascomycete fungi with worldwide distribution as saprophytes. ,,, The literature review shows that in humans, it is frequently associated with allergic respiratory diseases causing hay fever or hypersensitivity reactions that sometimes lead to asthma. It has also been described to cause keratitis, peritonitis, osteomyelitis, sinusitis and cutaneous as well as subcutaneous infections in immunocompromised hosts. ,,, Alternaria alternata and Alternaria infectoria are the most frequently encountered species in clinical samples; however, other species such as Alternaria triticina, Alternaria tenuissima, Alternaria chlamydospora, Alternaria longypes and Alternaria dianthicola have also been reported. ,,, The actual prevalence of these species is unknown, as a full identification has not been performed in most of the cases.
The diagnosis of Phaeohyphomycosis caused by Alternaria alternata is really difficult, but maintaining a high index of suspicion, particularly in immunocompromised hosts, can solve this critical issue, like in our case. ,,,,, Currently, the use of molecular techniques has been shown to be a useful method for the identification of Alternaria species using sequences of reference strains for comparison. ,, We have not used the molecular technique as the facility is not available at our institute.
Unfortunately, treatment is not standardized as most of the dematiaceous molds are susceptible to triazoles as well as amphotericin B; however, therapeutic failure is documented in several reports. In our case, we gave a trial of amphotericin B but did not achieve satisfactory response. There is no formal consensus regarding which specific agent should be used as well as the ideal duration of therapy, because clinical trials are lacking. ,,, The echinocandins are the most recent family of anti-fungal agents that have shown good activity against Alternaria alternata. Anidulafungin is the most active drug in this class, while Caspofungin is the least active one. ,, Surgery is probably the best treatment of well-delineated lesions. However, even when surgical excision is complete, additional medical treatment is advocated to avoid local sporotrichoid dissemination and to treat concomitant sub-clinical lesions, like in our case. ,,
In conclusion, we are reporting this unique case describing the association of visceral Phaeohyphomycosis caused by the opportunistic fungus Alternaria alternata with immunocompromised state in a young patient with insulin-dependent type-1 diabetes. The patient did not respond well to highly sensitive amphotericin B, resulting in eventual loss of the kidney. Therefore, detailed prospective studies are recommended to determine the epidemiological parameters, modes of clinical presentation and diagnostic as well as therapeutic strategies for the management of cutaneous, subcutaneous and visceral Phaeohyphomycosis caused by Alternaria alternata.
| Acknowledgment|| |
The authors are thankful to their dedicated team of pathology, radiology and pharmacy departments who helped in the diagnosis and management of this case.
Conflict of interest: None declared.
| References|| |
Revankar SG. Clinical and treatment aspects of brown black fungi. Curr Fungal Infect Rep 2010;4:46-51.
Gabardi S, Kubiak DW, Chandraker AK, Tullius SG. Invasive fungal infections and antifungal therapies in solid organ transplant recipients. Transpl Int 2007;20:993-1015.
Vermeire SE, de Jonge H, Lagrou K, Kuypers DR. Cutaneous phaeohyphomycosis in renal allograft recipients: Report of 2 cases and review of the literature. Diagn Microbiol Infect Dis 2010;68:177-80.
Pastor FJ, Guarro J. Alternaria infections: Laboratory diagnosis and relevant clinical features. Clin Microbiol Infect 2008;14:734-46.
Revankar SG. Dematiaceous fungi. Mycoses 2007;50:91-101.
Pastor FJ, Guarro J. Alternaria infections: Laboratory diagnosis and relevant clinical features. Clin Microbiol Infect 2008;14:734-46.
Ben-Ami R, Lewis RE, Raad II, Kontoyiannis DP. Phaeohyphomycosis in a tertiary care cancer center. Clin Infect Dis 2009;48:1033-41.
Naggie S, Perfect JR. Molds: Hyalohyphomycosis, phaeohyphomycosis, and zygomycosis. Clin Chest Med 2009;30:337-53, vii-viii.
Yehia M, Thomas M, Pilmore H, Van Der MW, Dittmer I. Subcutaneous black fungus (phaeohyphomycosis) infection in renal transplant recipients: Three cases. Transplantation 2004;77:140-2.
Farina C, Gotti E, Parma A, Naldi L, Goglio A. Phaeohyphomycotic soft tissue disease caused by Alternaria alternata in a kidney transplant patient: A case report and literature review. Transplant Proc 2007;39:1655-9.
Alastruey-Izquierdo A, Cuesta I, Ros L, Mellado E, Rodriguez-Tudela JL. Antifungal susceptibility profile of clinical Alternaria spp. Identified by molecular methods. J Antimicrob Chemother 2011;66:2585-7.
Ogawa MM, Galante NZ, Godoy P, et al. Treatment of subcutaneous phaeohyphomycosis and prospective follow-up of 17 kidney transplant recipients. J Am Acad Dermatol 2009;61:977-85.
Gomes J, Vilarinho C, Duarte Mda L, Brito C. Cutaneous Phaeohyphomycosis Caused by Alternaria alternata Unresponsive to Itraconazole Treatment. Case Rep Dermatol Med 2011;2011:385803.
Sabatelli F, Patel R, Mann PA, et al. In vitro activities of posaconazole, fluconazole, itraconazole, voriconazole, and amphotericin B against a large collection of clinically important molds and yeasts. Antimicrob Agents Chemother 2006;50:2009-15.
Lai CC, Tan CK, Huang YT, Shao PL, Hsueh PR. Current challenges in the management of invasive fungal infections. J Infect Chemother 2008;14:77-85.
Dr. R U Khan
Pakistan Atomic Energy Commission (PAEC) General Hospital, Sector H-11/4, Islamabad