Immunologic impairment can frequently occur in patients with nephrotic syndrome because of low serum immunoglobulin G concentrations, reduced complement activity, depressed T-cell function and the use of corticosteroids or cytotoxic agents . The immunologic impairment, adding the protein-rich edematous skin serving as a good media, increases the vulnerability to various cutaneous infections  (be reported in up to 27.02% ), particularly the cellulitis. The most common pathogens that cause cellulitis are β-hemolytic Streptococci and some gram-negative bacteria such as E.coli . But other atypical organisms shouldn’t be neglected considering the immunocompromised condition in nephrotic syndrome patients just as our case.
As important opportunistic pathogens, C. neoformans usually infect individuals with AIDS. Nevertheless, with an increasing number of steroid-dependent individuals as our patient in the last decade, the prevalence rate of cryptococcosis is continuously rising . In humans, C. neoformans usually cause three types of infections: pulmonary cryptococcosis, cryptococcal meningitis and wound or cutaneous cryptococcosis . Cutaneous involvement, a rare but important feature of disseminated cryptococcosis, may precede systemic symptoms by as long as 8 months . Naoko Ogami has report a patient with nephrotic syndrome suffering from primary cutaneous cryptococcosis without other organ involvement . However, cutaneous cryptococcal disease usually represents the hematogenous dissemination of cryptococcosis. Its presentation has various clinical morphologies: a draining sinus tract, verrucous nodules, molluscum-like lesions and erythematous, indurated plaques, and so on . Yet, none of these manifestations are pathognomonic for cryptococcal infection. Confusion with other resemble diseases is not uncommon and a diagnostic delay might be a major factor contributing to high associated mortality . A timely histological analysis of skin biopsies can assist to confirm the pathogens. In addition, the importance of CSF cultures and serological studies should not be over emphasized .
According to the current guidelines of the Infectious Diseases Society of America (IDSA), amphotericin B combined with flucytocine is recommended as primary therapy regimen for disseminated cryptococcosis followed by fluconazole as consolidation therapy . To those with renal dysfunction, lipid formulations of AmB or AmB lipid complex could replace Am B to avoid further deterioration of the renal function. With appropriate systemic antifungal therapy, 74% of patients with cryptococcal cellulitis can be expected to survive in immunocompetent status . However, to those having developed into organ failures, as seen in our patients, a review of the literature suggests a much graver prognosis. The mortality rate of ARF result from disseminated cryptococcosis was 100% and 55% respectively in immunocompromised patients with or without AIDS [5, 18], and nearly all deaths occurred within 2 weeks of diagnosis with or without treatment indicating an aggressive and fulminant progress of the disease.
There are several potential explanations for the poor prognosis of our patients. First, a severe disseminated cryptococcal infection that caused multiple organ failure lead to the poor outcome. Second, the delayed diagnosis and antifungal therapy have also been a contributing factor. Finally, the patients’ suddenly deteriorated condition after two day’s antifungal therapy reminded that immune reconstitution inflammatory syndrome (IRIS) might also have contributed to his death. The IRIS which manifests with inflammatory reactions, targeted at the antigens of opportunistic infections can occur in immunocompromised patients after some degree of immune restoration . If the IRIS occurs in patients already diagnosed with opportunistic infections, it may result in recurrence or worsening of clinical features despite effective treatment . It has been reported that in patients with cryptococcal meningitis, antifungal therapy may prompt the reversion of an immunosuppressive Th2 response to the normally protective Th1 cytokine response, leading to an exuberant host response against residual sites of disease . Because we didn’t monitor the changes of T cells in our patient, the IRIS as a risk factor can’t be excluded completely.
In conclusion, this case demonstrated that C. neoformans should be considered in the differential diagnosis of cutaneous infection in nephrotic patients or other immunosuppressive patients. Even when the organism is clear, one can't be too cautious to reconsider the potential existence of other atypical pathogens if the initial treatment makes little effects.