Home About us Current issue Ahead of Print Back issues Submission Instructions Advertise Contact Login   

Search Article 
Advanced search 
Saudi Journal of Kidney Diseases and Transplantation
Users online: 259 Home Bookmark this page Print this page Email this page Small font sizeDefault font size Increase font size 

Table of Contents   
Year : 2012  |  Volume : 23  |  Issue : 1  |  Page : 102-105
Primary cutaneous cryptococcosis due to Cryptococcous laurentii in a renal transplant recipient

1 Department of Critical Care Medicine, Apollo Hospitals, Bangalore, India
2 Department of Microbiology, Apollo Hospitals, Bangalore, India
3 Department of Nephrology, Apollo Hospitals, Bangalore, India

Click here for correspondence address and email

Date of Web Publication3-Jan-2012


We report a patient with primary cutaneous cryptococcosis caused by Cryptococcous laurentii following renal transplantation, probably due to repeated insulin and heparin subcutaneous injections on his thigh. Although cutaneous cryptococcosis due to C. neoformans is well known, reports of skin infections due to non-neoformans cryptococci are uncommon.

How to cite this article:
Kulkarni A, Sinha M, Anandh U. Primary cutaneous cryptococcosis due to Cryptococcous laurentii in a renal transplant recipient. Saudi J Kidney Dis Transpl 2012;23:102-5

How to cite this URL:
Kulkarni A, Sinha M, Anandh U. Primary cutaneous cryptococcosis due to Cryptococcous laurentii in a renal transplant recipient. Saudi J Kidney Dis Transpl [serial online] 2012 [cited 2022 Aug 16];23:102-5. Available from: https://www.sjkdt.org/text.asp?2012/23/1/102/91311

   Introduction Top

Cryptococcal infection in renal transplant recipients occurs almost exclusively four months post transplant. [1] The incidence of infection varies between 0.8 to 5.8% depending on the type and severity of immunosuppression. [2] There are several reports of cryptococcosis due to C. neoformans in transplant recipients. Non-neo-formans cryptococcus were previously considered saprophytes and were thought to be non-pathogenic; however, there have been an increasing number of case reports on infection by this fungus. [3] There have been only two case reports of cutaneous cryptococcosis due to Cryptococcus laurentii till date. [4],[5] Our case is the only reported case of primary cutaneous cryptococcosis (PCC) by C. laurentii, probably caused by repeated inoculations and skin injury by insulin and low-molecular weight heparin injections on the thigh in a renal allograft recipient.

   Case Report Top

A 55-year-old male was admitted to our hospital in August 2007 with complaints of respiratory distress, multiple cutaneous lesions on left thigh and nasal bleeding. The patient was a known diabetic for the past 20 years and a hypertensive for the past six years. He was diagnosed to have end-stage renal disease secondary to diabetic nephropathy for which he received an allograft from his sister in June 2006 in another hospital. He received steroids, mycophennolate mofetil and cyclosporine as his immunosuppressive regimen. He had stable graft function in the immediate post-operative period. On the 10th day post transplant, he developed ischemic stroke leading to right hemiparesis. Six months later, he had gangrene of his right great toe, which was eventually amputated and followed by vascular surgery for ischemic limb. Because of multiple ischemic vascular events, he was started on oral anticoagulants. Nine months post-transplant, he was admitted for evaluation of his allograft dysfunction (creatinine 3.5 mg/dL). He underwent a kidney biopsy, which revealed an acute cellular rejection, and he was treated with pulse methylprednisolone. Cyclosporine was withdrawn and rapamycin was introduced. He was discharged with the advice to continue insulin and low molecular heparin injections.

Subsequently, the patient came to our hospital with respiratory distress, multiple cutaneous lesions on left thigh and nasal bleeding. On examination, he was afebrile with pulse - 92/m, BP 100/70 mmHg and respiratory rate 28-30/min SpO 2 88% on room air. He had pallor, and examination of his left thigh revealed multiple necrotic, umbilicated lesions with raised edges and multiple satellite lesions [Figure 1]A. The surrounding area was indurated, erythematous and tender.
Figure 1: A: Patient's left thigh showing multiple necrotic, umbilicated lesions with raised edges and multiple satellite lesions.
B: Skin biopsy (PAS stain) showing large groups of deep magenta staining structures suggestive of cryptococci.
C and D: Sabouraud's dextrose agar with the mucoid colonies of C. laurentii and Gram's stain from the same showing budding yeast cells.

Click here to view

The systemic examination revealed signs of consolidation in the base of the right lung. The central nervous system (CNS) examination confirmed old right hemi-paresis with right upper limb contracture. No signs of meningoencephalitis were evident. A chest X-ray revealed basal consolidation in the right lung with pleural effusion. The patient underwent bronchoscopy, which showed inflamed right lower lobe bronchus.

The patient was started on oxygen therapy, non-invasive ventilatory support and broad-spectrum antibiotics. An ENT consultation was sought for nasal bleed and oral anti-coagulants were discontinued. The ENT examination revealed a healthy local mucosa, with no ulceration or blackening. An anterior nasal packing was performed to control the nasal bleed.

Bronchoalveolar lavage and sputum grew Candida albicans. A skin biopsy showed a minimal inflammatory response on routine hematoxylin and eosin preparation. On PAS stain, however, large groups of deep magenta staining cryptococci showed up in hair follicles, sweat and sebaceous glands. Many were also lying freely in the dermis; granuloma formation was not evident [Figure 1]B. The biopsy material was sent for microbiological examination.

Gram's stain showed occasional round to oval budding yeast cells; the capsules around the yeast cells were not appreciable. Culture isolated the yeast, which was urease producing, and caffeic acid test was negative. The yeast was subsequently identified as Cryptococcus laurentii (API ID 32 C, bioMerieux), and was sensitive to flucytosine and resistant to amphotericin B, fluconazole, itraconazole and voriconazole (ATB fungus 3 system, bioMerieux) [Figure 1]C and D.

In view of deranged coagulation parameters and low hemoglobin, the patient was transfused with packed cells and fresh frozen plasma. Blood sugar was uncontrolled on admission and required insulin infusion. The patient required initiation on hemodialysis three times a week because of deteriorated renal function.

Awaiting fungal culture sensitivity report, he was started on amphotericin B infusion. After the availability of the culture report, flucytosine was added to the existing regimen. His general condition improved during hospitalization, with improvement in respiratory symptoms. Cellulitis and induration surrounding the skin lesion also improved. He was eventually discharged at request with advice to continue amphotericin B and flucytosine and intermittent hemodialysis. On the 7th day post discharge, he succumbed to the illness at his home.

   Discussion Top

Incidence of cryptococcal infection varies from 0.8 to 5.8% depending on the type and intensity of immunosuppression. [2] The described case was immunocompromised due his longstanding diabetic status, post-transplant status, triple immunosuppressive agents and also recent pulse steroid therapy. The patient had a predisposition to skin injury due to multiple subcutaneous injections, which increased his risk for C. laurentii infection. [6] The presence of invasive devices is a significant risk factor associated with C. laurentii infections. [7]

Although cutaneous cryptococcosis in most immunocompromised patients is a sign of disseminated disease, it is known to occur as a primary disease where skin serves as the primary portal of entry. There are now increasing number of case reports of PCC, reiterating this fact. [2],[8],[9] The patient had multiple skin lesions without evidence of disseminated cryptococcal infection.

Neuville et al in his review found PCC patients to be older (59 versus 40 in SCC), less immmunosuppressed, more predisposed to skin injury and with no gender difference as compared with SCC patients. [6] Although PCC is known to cause solitary lesions, the present case had multiple umbilicated lesions, which could be attributed to multiple cutaneous injections.

The most common dermatological feature of PCC is whitlow, followed by cellulites, nodules and ulcers on exposed areas. Skin lesions in SCC are usually multiple, scattered, located on both exposed and clothed areas. Umbilicated papules resembling molluscum contagiosum, bullae, pustules, abscesses, acneform lesions, herpetiform lesions, Kaposi's sarcoma or basal cell carcinoma-like nodules, extensive cellulites, pyoderma gangrenosum-like lesions and a combination of polymorphic lesions are also seen in SCC.

Till today, there have been only 16 case reports of infections caused by C. laurentii. These infections include lung infections - 2, peritonitis - 2, eye infections - 2, meningitis - 1, fungemia - 7 and two cases of cutaneous infection. [2] The first case of cutaneous infection caused by C. laurentii was attributed to remote dog bite and the second was a case of secondary cutaneous cryptococcosis.

The first clues to the diagnosis of cryptococcus infection are India ink preparation showing capsulated budding yeast cells and culture showing mucoid colonies. In our case, even though the India ink preparation from the skin biopsy was negative, yeast cells were observed in the Gram's stain and cryptococcus was subsequently isolated. The fungus was notably absent from blood and lungs. Central nervous system involvement was unlikely as the patient did not have any neurological signs and symptoms. Furthermore, CSF was deferred in view of the patient's abnormal coagulation parameters. The serum cryptococcus latex agglutination test was negative. The review of the previous cases of C. laurentii infections also found the cryptococcal antigen detection test to be either not done or consistently negative. [7]

Histopathology in cutaneous cryptococcosis may reveal two types of tissue responses. In immmunosuppressed patients, the organism may evoke minimal or no inflammatory response, as was in this case, while it may produce a granulomatous reaction composed of macrophages, lymphocytes and foreign body giant cells in immunocompetent patients or those with protracted disease. [10]

As there are limited case reports of PCC caused by C. laurentii, standard recommendations regarding its treatment are lacking. [7] Correlation between in vitro antifungal susceptibility test results and treatment outcome is not reported for C. laurentii.

Treatment of cryptococcal disease depends on the anatomic site of involvement and host immune status. The mainstay of treatment for cryptococcosis is amphotericin B with or without 5-flucytosine. Azoles have recently emerged as alternate drugs in noncompliant patients. [11] A report on the practice guideline for the management of cryptococcal infection recommended use of azoles for non-CNS cryptococcal infections, including cutaneous disease. [12] However, our patient received parenteral amphotericin B, and 5-flucytosine was added subsequently in view of the fungal sensitivity report. He was discharged as the dermatological lesions were found to be healing gradually and due to alleviation in the other symptoms. The cause of his death could not be ascertained.

This is, to our knowledge, the first report of PCC due to C. laurentii in an immunocompromised host. Reporting of such patients might further expand the existing spectrum of the clinical manifestations of the disease. Awareness and high index of suspicion might assist in early diagnosis and institution of treatment.

   References Top

1.Rubin RH. Infection of the renal and liver transplant patient. In. Rubin RH and Young LS (eds). Clinical approach to infection in the compromised host. New York: Plenum Medical. 1988:557-621.  Back to cited text no. 1
2.Gupta RK, Khan ZU, Nampoory MR, Mikhail MM, Johny KV. Cutaneous cryptococcosis in a diabetic renal transplant recipient. J Med Microbiol 2004;53:445-9.  Back to cited text no. 2
3.Cheng MF, Chiou CC, Liu YC, Wang HZ, Hsieh KS. Cryptococcus laurentii fungemia in premature neonate. J Clin Microbiol 2001;39 (4):1608-11.  Back to cited text no. 3
4.Kamalam A, Yesudian P, Thambiah AS. Cutaneous infection by Cryptococcus laurentii. Br J Dermatol 1977;97:221-3.  Back to cited text no. 4
5.Vlchkova-Lashkoska M, Kamberova S, Starova A, et al. Cutaneous Cryptococcus laurentii infection in human immunodeficiency virusnegative subject. Eur Acad Dermatol Venereol 2004;18:99-100.  Back to cited text no. 5
6.Neuville S, Dromer F, Morin O, Dupont B, Ronin O, Lortholary O. French Cryptococcosis Study Group. Primary cutaneous cryptococcosis: a distinct clinical entity. Clin Infect Dis 2003;36(3):337-47  Back to cited text no. 6
7.Khawcharoenporn T, Apisarnthanrak A, Mundy LM. Non neoformans Cryptococcal infections: A systemic review. Infection 2007;35(2):51-7.  Back to cited text no. 7
8.Quartarolo N, Thomas I, Li H, Wiederkehr M, Schwartz RA, Lambert WC. Cutaneous cryptococcosis. Acta Dermatovenerol 2002;11(4): 1581-2979.  Back to cited text no. 8
9.Christianson JC, Engber W, Andes D. Primary cutaneous Cryptococcosis in immunocompetent and immunocompromised hosts. Med Mycol 2003;41(3):177-88.  Back to cited text no. 9
10.McAdam AJ, Sharpe AH. Infectious diseases. In Kumar V, Abbas A, Fausto N (Editors). Robbins and Cotran Pathologic basis of disease. 7 th Ed. Saunders pub, Philadephia. 2004: 399.  Back to cited text no. 10
11.Hussain S, Wagener MW, Singh N. Crypto-coccus neoformans infection in organ transplant recipients: Variables influencing clinical characteristics and outcome. Emerg Inf Dis 2001;7:375-81.  Back to cited text no. 11
12.Saag MS, Graybill RJ, Larsen RA, et al. Practice Guidelines for the Management of Cryptococcal Disease. Clin Infect Dis 2000;30:710-8.  Back to cited text no. 12

Correspondence Address:
Urmila Anandh
Consultant Nephrologist, Kokilaben Dhirubhai Ambani Hospital, Four Bungalows, Andheri (West), Mumbai
Login to access the Email id

Source of Support: None, Conflict of Interest: None

PMID: 22237228

Rights and PermissionsRights and Permissions


  [Figure 1]

This article has been cited by
1 Cryptococcus laurentii Fungemia
Banerjee, P. and Haider, M. and Trehan, V. and Mishra, B. and Thakur, A. and Dogra, V. and Loomba, P.
Indian Journal of Medical Microbiology. 2013; 31(1): 75-77
2 Cutaneous cryptococcosis in solid organ transplant recipients: Epidemiological, clinical, diagnostic and therapeutic features
Biancheri, D. and Kanitakis, J. and Bienvenu, A.-L. and Picot, S. and Morelon, E. and Faure, M. and Euvrard, S.
European Journal of Dermatology. 2012; 22(5): 651-657


    Similar in PUBMED
    Search Pubmed for
    Search in Google Scholar for
    Email Alert *
    Add to My List *
* Registration required (free)  

   Case Report
    Article Figures

 Article Access Statistics
    PDF Downloaded637    
    Comments [Add]    
    Cited by others 2    

Recommend this journal