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Table of Contents
CASE REPORT
Year : 2019  |  Volume : 13  |  Issue : 2  |  Page : 138-140

Disseminated cutaneous cryptococcal infection in kidney transplant recipient


Department of Nephrology, Care Hospitals, Hyderabad, Telangana, India

Date of Submission19-Sep-2018
Date of Acceptance10-Jan-2019
Date of Web Publication28-Jun-2019

Correspondence Address:
Dr. Suhas Dilip Mondhe
S/O Dilip Mondhe, 501 Venkatesh Park Apt., Sutarwadi Link Road, Near Sai Chowk, Pashan, Pune - 411 021, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_58_18

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  Abstract 


Postkidney transplant infectious complications are always challenging due to atypical organisms, varied presentation, and the balanced treatment to avoid rejection. They are often fatal if not diagnosed and treated in time. High clinical suspicion and decreasing immunosuppression are the important points to remember. This is a case report of postkidney transplant recipient with disseminated cryptococcal infection. The patient improved with functioning graft with appropriate antifungal treatment.

Keywords: Disseminated cryptococcal, kidney transplant, transplant infection


How to cite this article:
Mondhe SD, Kumthekar GV, Hedau S, Reddy P V, Gundlapalli S. Disseminated cutaneous cryptococcal infection in kidney transplant recipient. Indian J Transplant 2019;13:138-40

How to cite this URL:
Mondhe SD, Kumthekar GV, Hedau S, Reddy P V, Gundlapalli S. Disseminated cutaneous cryptococcal infection in kidney transplant recipient. Indian J Transplant [serial online] 2019 [cited 2019 Jul 19];13:138-40. Available from: http://www.ijtonline.in/text.asp?2019/13/2/138/261844




  Introduction Top


Infectious complications are common in the posttransplant period due to immunosuppressed state. Tuberculosis and bacterial infection are more common as compared to fungal infection. Disseminated fungal infections are often life-threatening. We report a case of disseminated cryptococcal infection presented with cellulitis leg.


  Case Report Top


A 59-year-old male presented with a known case of diabetes mellitus type 2, hypertension, dilated cardiomyopathy, and chronic kidney disease. He underwent live related renal allograft recipient status in 2012. The donor was brother of the patient. He received glucocorticoid as an induction agent. He was on triple-drug immunosuppression with tacrolimus, mycophenolate mofetil, and glucocorticoids. After 5 years, renal biopsy showed chronic allograft nephropathy in 2017. The last creatinine was 3.0 mg/dl before the presentation. Immunosuppression was modified accordingly.

The patient developed bilateral leg pain with swelling along with redness and continuous fever [Figure 1]. He was diagnosed to have cellulitis in both the legs (sites involving medial part of the right thigh, lateral part of the right leg, and posterior part of the left leg) and started on empirical antibiotics with Gram-positive and Gram-negative coverage. Drug dosages were adjusted as per renal functions. The wound debridement was done. The pus examination revealed encapsulated yeast forms and culture confirmed Cryptococcus. He was diagnosed to have disseminated Cryptococcus infection in view of the involvement of noncontiguous sites. He was started on fluconazole and liposomal amphotericin B injections. The patient's immunosuppression was tapered as the wound healing was hampered. Tacrolimus was stopped and mycophenolate mofetil was given with half dose. Prednisolone was changed to hydrocortisone. The patient had worsening of renal functions and initiated on hemodialysis in view of worsening renal parameters.
Figure 1: Multiple (noncontagious) cutaneous cryptococcal lesions before treatment

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As the sites involved were noncontagious assuming the same source, transthoracic two-dimensional echo was done. There was a mobile mass of 0.5 cc on the noncoronary cusps of the aortic valve [Figure 2] and [Figure 3]. Blood cultures were sent as per infective endocarditis protocol and blood culture was positive for cryptococcal infection. There was no central venous catheter or recent history of any prolonged internal jugular vein cannulation. The wound healing was better after reducing immunosuppression. During the treatment, the patient received 2 weeks of the liposomal amphotericin B along with fluconazole 400 mg/day. As tacrolimus can have drug reactions with fluconazole which is important for the treatment, instead of mycophenolate mofetil, tacrolimus was stopped. As we wanted to achieve lesser cumulative immunosuppression, mycophenolate dose also decreased to half. Liposomal amphotericin B was stopped after 2 weeks and only fluconazole oral 400 mg/day continued. Hence, at discharge, the patient was on prednisolone 5 mg OD, mycophenolate 250 mg BD, and fluconazole 400 mg OD.
Figure 2: Highlighted mobile mass on the noncoronary cusp of the aortic valve

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Figure 3: Transthoracic two-dimensional echo with mitral (white arrow) and tricuspid (yellow arrow) valves without involvement

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Apart from skin and heart, no other organs were involved. No lung or brain lesions were not there, which were confirmed after imaging. Now, the patient's wound healing is good with better renal functions after 3 weeks of treatment [Figure 4]. The hemodialysis was stopped.
Figure 4: Multiple (noncontagious) cryptococcal lesions after treatment

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  Discussion Top


Cryptococcus is the third most common fungal infection postcandidiasis and aspergillosis in organ transplant recipient.[1] Cryptococcal fungus is now recognized with total seven species with gattii/neoformans complex.[2] Most commonly, cryptococcal infection involves meningitis and pneumonia, but other forms such as myocardium, bones, joints, urinary tract, skin, and soft tissue are reported. The incidence of the cryptococcal infection is mostly seen in HIV patients but is not uncommon for non-HIV patients. The incidence of the cutaneous cryptococcal infection is approximately 10%–20%, and the mortality in reported cases is 25%.[3] Cutaneous cryptococcal infection is mostly hematogenous spread from a distant organ; mostly, lungs are the portal of entry, i.e., secondary cutaneous cryptococcal infection. Primary cutaneous cryptococcal infection is rare and occurs due to direct trauma. Papules, pustule, plaque, nodule ulcer, and cellulitis are different presentations of the cutaneous cryptococcal infection.[4]

The microbiological investigation in the form of blood fungal culture and serum cryptococcal antigen (latex cryptococcal antigen agglutination test) are the gold standards to diagnose noncentral nervous system (CNS) cryptococcal infection. Due to the polysaccharide capsule of Cryptococcus, India ink is used for negative staining.[1]

The virulence factors of cryptococcal strains are polysaccharide capsule, phenotyping switching of the strains, and presence of the phenoloxidase enzyme. The enzyme phenoloxidase catalyzes the conversion of phenolic compounds to melanin. Melanin contributes to the virulence by acting as an antioxidant and protect from immune effector cells.[5]

Necrotizing fasciitis is one of the types of skin infection in which the infection spreads to the soft-tissue planes. This is a rapidly progressing condition, associated with significant morbidity and mortality. In posttransplant patients, the risk factors are present such as associated comorbidities diabetes mellitus, chronic kidney disease, induction agents, and immunosuppressive medications. The lower extremities are more common, and unlike bacterial infection, cryptococcal infection is bilateral. Being a disseminated infection, another organ involvement is possible.[6]

Cryptococcus neoformans incidence in organ transplant patients is reported as 2.8% (overall death rate: approximately 42%). The use of tacrolimus is associated with less CNS involvement, but non-CNS infections (skin, soft tissue, and bones) are reported more. Renal failure at admission was the only independently significant predictor of death in these patients.[7]

Infective endocarditis involving native valves and immunocompetent hosts is comparatively rare than prosthetic valves and immunocompromised hosts. Fungal endocarditis corresponds to approximately 6% of all the infective endocarditis patients. Among the cases of fungal endocarditis, Candida, Aspergillus, Histoplasma, and Cryptococcus are the most common fungi to cause infective endocarditis. Several case reports suggest to use amphotericin B in the treatment of cryptococcal endocarditis, either with surgery or without surgery. Case reports are available showing use of Amphotericin B followed by Fluconazole with good outcomes.[8] Oral fluconazole 400 mg/day continued for the next 6 months.

Once the diagnosis is confirmed, treatment management mainly depends on antifungal choice and decreases the immunosuppressive medications. There are no studies for the non-CNS and nonpulmonary cryptococcal infections in immunocompromised patients. Patients are normally treated with fluconazole (6 mg/kg/day) for 6–12 months.[9] Systemic treatment injectable amphotericin B deoxycholate or liposomal preparation along with or without fluconazole is given.


  Conclusion Top


Infections in immunocompromised hosts often present in an atypical way. Disseminated cryptococcal infection is although rare but life-threatening in renal transplant recipients. Hence, timely diagnosis and optimizing immunosuppression is the key to management.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Chaya R, Padmanabhan S, Anandaswamy V, Moin A. Disseminated cryptococcosis presenting as cellulitis in a renal transplant recipient. J Infect Dev Ctries 2013;7:60-3.  Back to cited text no. 1
    
2.
Hagen F, Khayhan K, Theelen B, Kolecka A, Polacheck I, Sionov E, et al. Recognition of seven species in the Cryptococcus gattii/Cryptococcus neoformans species complex. Fungal Genet Biol 2015;78:16-48.  Back to cited text no. 2
    
3.
Gave AA, Torres R, Kaplan L. Cryptococcal myositis and vasculitis: An unusual necrotizing soft tissue infection. Surg Infect (Larchmt) 2004;5:309-13.  Back to cited text no. 3
    
4.
Lu YY, Wu CS, Hong CH. Primary cutaneous cryptococcosis in an immunocompetent man: A case report. Dermatol Sin 2013;31:90-3.  Back to cited text no. 4
    
5.
Wang Y, Aisen P, Casadevall A. Cryptococcus neoformans melanin and virulence: Mechanism of action. Infect Immun 1995;63:3131-6.  Back to cited text no. 5
    
6.
Baer S, Baddley JW, Gnann JW, Pappas PG. Cryptococcal disease presenting as necrotizing cellulitis in transplant recipients. Transpl Infect Dis 2009;11:353-8.  Back to cited text no. 6
    
7.
Husain S, Wagener MM, Singh N. Cryptococcus neoformans infection in organ transplant recipients: Variables influencing clinical characteristics and outcome. Emerg Infect Dis 2001;7:375-81.  Back to cited text no. 7
    
8.
Roy M, Ahmad S, Roy AK. Cryptococcus neoformans infective endocarditis of native valves in an immunocompetent host. IDCases 2018;12:66-70.  Back to cited text no. 8
    
9.
Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR, Hamill RJ, et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 Update by the Infectious Diseases Society of America. Clin Infect Dis 2010;50:291-322.  Back to cited text no. 9
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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