Fever, rash, and muscle tenderness. A distinctive clinical presentation of disseminated candidiasis

Five patients had fatal, disseminated candidiasis. At the onset of candidemia, a remarkably similar and distinctive triad of high fever, papular erythematous skin lesions, and diffuse severe muscle tenderness developed in each patient. This previously unreported clinical syndrome is sufficiently unique to justify a presumptive diagnosis of disseminated candidiasis and the use of empiric antifungal therapy pending culture and biopsy results.     

Cutaneous lesions in disseminated candidiasis mimicking ecthyma gangrenosum

Cutaneous nodules are recognized as a manifestation of disseminated candidiasis. We describe skin lesions clinically identical to ecthyma gangrenosum that, on microscopic examination, were due to Candida emboli rather than Pseudomonas sepsis.Thus, the appearance of necrotic pustules and ulcerative plaques in the immunocompromised patient would raise the possibility of Candida as well as Pseudomonas sepsis, and illustrates the diagnostic importance of skin biopsy in such cases.     

Candida arthritis. A manifestation of disseminated candidiasis.

Fungal infections infrequently involve the joints. Review of the literature reveals that Candida arthritis is rare, that it is usually a complication of disseminated candidiasis and that it occurs as a primary joint infection without spread from adjacent osteomyelitis. In the patient we describe Candida arthritis and bursitis of separate joints developed as a late manifestation of disseminated infection following "transient" C. tropicalis fungemia. Treatment consisting of aspiration and parenteral amphotericin B eradicated the joint infection without the need for surgery. Bursectomy, however, was required to eradicate the bursal infection. Awareness of this as well as other late complications of candidemia which signify disseminated infection is important. Optimal therapy will be determined only by further clinical experience with this unusual manifestation of Candida infection.     

Candida osteomyelitis. Report of five cases and review of the literature

Candida species have emerged as important pathogens in human infection. Although a variety of deep-seated candidal infections have been reported, Candida osteomyelitis has rarely been described. Five patients with Candida osteomyelitis are presented, and the 32 adult cases previously reported are reviewed. Candida osteomyelitis is noted as a simultaneous occurrence or late manifestation of hematogenously disseminated candidiasis. Osteomyelitis may not be prevented by a course of amphotericin B adequate to control the acute episode of disseminated candidiasis, particularly in immunosuppressed patients. Less commonly, Candida osteomyelitis presents as a postoperative wound infection. Like bacterial osteomyelitis, the most common presenting symptom is local pain. The insidious progression of infection, the nonspecificity of laboratory data, and the failure to recognize Candida as a potential pathogen may lead to diagnostic delay. Diagnosis can be made by either open biopsy or closed needle aspiration. Successful therapeutic regimens have employed combinations of antifungal therapy (most often amphotericin B) with surgical debridement when indicated. It is anticipated that osteomyelitis will become a more commonly recognized manifestation of hematogenously disseminated candidiasis.     

Fatal disseminated Scedosporium inflatum infection in a neutropenic immunocompromised patient.

Disseminated infection with the fungus Scedosporium inflatum in a neutropenic patient with non-Hodgkins lymphoma presented with the triad of muscle tenderness, papular skin lesions and fever, and progressed rapidly to a fatal outcome. This represents the first reported instance of fatal widely disseminated infection with this organism, and demonstrates that the triad of presenting clinical features, formerly reported to be pathognomic of systemic candidiasis, can no longer be regarded as specific for infection with a particular species of yeast or fungus.     

Cryptococcal disease presenting as cellulitis.

Three immunocompromised patients presented with cellulitis as the primary manifestation of cryptococcal disease. Two were recipients of cadaveric renal transplants who were receiving immunosuppressive drug therapy. The other patient had profound lymphopenia and severe hypoalbuminemia due to intestinal lymphangiectasia. All had failed to respond to empiric therapy for presumed bacterial cellulitis before results of skin biopsy or aspiration were available for the correct diagnosis to be made. With administration of systemic antifungal therapy, two patients survived. Although other forms of cryptococcal involvement of the skin are not rare, cellulitis is seldom considered to be a cutaneous manifestation of the disease. Our cases and a review of the English-language literature indicate that Cryptococcus neoformans must be included in the differential diagnosis of cellulitis in immunocompromised patients and that the presence of cryptococcal cellulitis suggests disseminated cryptococcal disease. Prompt diagnosis and treatment may dramatically reduce mortality.     

Effects of preventive, early, and late antifungal chemotherapy with fluconazole in different granulocytopenic models of experimental disseminated candidiasis

To investigate the potential use of fluconazole for prevention and treatment of disseminated candidiasis in granulocytopenic patients, its in vivo antifungal activity was studied in three models of disseminated candidiasis in persistently granulocytopenic rabbits: acute, subacute, and chronic disseminated candidiasis. Fluconazole was compared with the combination of amphotericin B and flucytosine for preventive, early, and late treatment of disseminated candidiasis, depending on the model. Fluconazole was most effective when used for preventive or early treatment of acute and subacute disseminated candidiasis. When compared with the combination of amphotericin B plus flucytosine, fluconazole was similarly effective in early treatment of acute and subacute disseminated candidiasis. When treatment was delayed 6 days after established infection, fluconazole was less active in clearing tissues in comparison with its activity in preventive and early treatment. The combination of amphotericin B plus flucytosine, however, was significantly more active than fluconazole in treatment of chronic disseminated candidiasis in all tissues. In summary, fluconazole was most effective against disseminated candidiasis in persistently granulocytopenic rabbits when used for prevention or early treatment.     

A case of disseminated candidiasis as an initial presentation of AIDS

A 44-year-old woman referred for skin eruptions and an altered mental status was confirmed to have HIV infection on Western Blot analysis. Her CD4+ T cell count was 15/microl. On admission, she appeared quite ill with respiratory distress. Chest X-ray showed bilateral patchy infiltration and pleural effusions. She was treated with cefotaxime, pentamidine, and antituberculosis drugs, but her condition worsened and dopamine was initiated. Intensive treatment failed, and she died the following day. An autopsy showed purplish papules on her face and trunk and multiple white nodules in her liver, spleen and lungs. Culture was positive for Candida Albicans, yielding a diagnosis and of disseminated candidiasis. It is rare for HIV patients to be diagnosed with disseminated candidiasis, since the pathogenesis usually requires disruption of the mucosal barrier. The defense mechanism against disseminated candidiasis is mainly neutrophils and macrophages, and its dysfunction is not a primary characteristic of HIV infection. To the best of our knowledge, this is the first report in Japan of a HIV patient to have disseminated candidiasis.     

Pyomyositis with hepatic and perinephric abscesses caused by Candida albicans in a diabetic nephropathy patient

Both disseminated candidiasis and pyomyositis are rare and mainly encountered in severely immunocompromised hosts. To our knowledge, Candida albicans related pyomyositis with formation of multiple visceral abscesses in a diabetic nephropathy patient has never previously been reported. A 47-year-old man with diabetic nephropathy and alcoholic liver disease developed disseminated candidiasis, with the initial presentation of pyomyositis. Debridement was performed and intravenous fluconazole commenced. Despite development of a single hepatic and multiple perinephric abscesses, the patient made a full recovery after completion of a 12-week course of intravenous fluconazole therapy. Candida species should be considered a potential pathogen in patients with predisposing factors.     

Deeply invasive candidiasis

The incidence of invasive candidiasis is on the rise because of increasing numbers of immunocompromised hosts and more invasive medical technology. Recovery of Candida spp from several body sites in a critically ill or immunocompromised patient should raise the question of disseminated disease. Although identification to the species level and antifungal susceptibility testing should guide therapy, at this time amphotericin B preparations are the usual initial therapy for severe life-threatening disease. Azole therapy has an expanding body of evidence that proves it is as effective as and safer than amphotericin B therapy. Some forms of candidiasis (e.g., those with ocular, bone, or heart involvement) require a combined medical and surgical approach.     

Hematogenous candida osteomyelitis. Report of three cases and review of the literature.

Candida osteomyelitis of the spine and intervertebral disc developed in three patients without evidence of back trauma of overlying cutaneous infection.Two patients were prone to the development of disseminated candidiasis by the use of multiple antibiotics and other predisposing modalities following abdominal surgery. One patient had no identifiable cause for development of the infection. The diagnosis was established in all three cases by x-ray evidence of osteomyelitis and culture from needle aspirate. Two patients had bone scans consistent with infection. Each patient received different therapy. One was treated with amphotericin B, one with spinal fusion and 5-fluorocytosine, and one with no antifungal therapy. All patients had complete healing of the involved vertebrae. Candida organisms have the potential to cause destructive bone infection following hematogenous dissemination. The presence of Candida osteomyelitis may be helpful in diagnosing disseminated candidiasis.     

Successful treatment of chronic disseminated candidiasis with fluconazole and a granulocyte-macrophage colony-stimulating factor combination.

We report a case of chronic disseminated candidiasis in a patient with acute non-lymphoid leukaemia. After 12 months of combined therapy with fluconazole and granulocyte-macrophage colony-stimulating factor, lesions in the liver and spleen resolved completely. The patient has given birth to a healthy baby and has been in complete hematological remission for 3 years.     

An open study on the safety and efficacy of fluconazole in the treatment of disseminated Candida infections in patients treated for hematological malignancy

Disseminated candidiasis is a serious infectious complication with a mortality as high as 50%. Standard therapy consists of parenteral amphotericin B which is associated with major side effects and prolonged hospitalization. The aim of the study was to assess the efficacy and safety of fluconazole in an open, noncomparative study. Fluconazole, as a single agent, was given intravenously for the first 3 days at a dose of 200 mg twice daily, followed by 200 mg twice daily orally until resolution of signs and symptoms or evident treatment failure. The study group comprised 24 consecutive patients of whom nine had acute and 15 chronic disseminated candidiasis. A clinical response was achieved in 67% of cases of acute disseminated candidiasis and in 86% of cases of chronic disseminated candidiasis. The median duration of therapy was 15 days and 6 months, respectively. Superinfections withAspergillus fumigatus developed in five patients who were persistently neutropenic. No drug-related toxicity was registered.     

Cutaneous histoplasmosis.

Cutaneous lesions as a manifestation of histoplasmosis, primarily a disease of the respiratory system, are rare and most commonly appear secondary to progressive dissemination. A patient with documented progressive, disseminated histoplasmosis, having been treated previously with amphotericin B, presented on a second occasion with cutaneous lesions as the chief complaint. Biopsy and cultures of these lesions were positive for Histoplasma capsulatum. A review of the English literature revealed only 7 reported cases of secondary skin histoplasmosis in the past 20 years. All patients, including the current one, either had diseases associated with depressed immunity or were receiving steroid therapy.     

Delayed diagnosis of multiple systemic disseminated tuberculosis: A case report

Rationale:The clinical manifestations in patients with disseminated tuberculosis (TB) are nonspecific and may present challenges for early diagnosis.Patient concerns and diagnoses:We describe the case of a 44-year-old man who presented with abdominal pain and discomfort for more than a month. He had undergone surgery for a chest wall abscess 9 months ago. Computed tomography scans showed a miliary pattern in the lung and multiple abscesses in the liver, spleen, left psoas major muscle, skin, and soft tissue, with rim enhancement. Mycobacterium tuberculosis was detected in the drainage fluid of the abscesses and surgical slices, and disseminated TB was diagnosed.Interventions and outcomes:With anti-tuberculosis therapy, the abscesses were gradually absorbed and all cultures were negative.Lessons:The patient exemplifies the difficulty of the early diagnosis of disseminated TB. Disseminated TB should be considered first in patients with multisystem illness, and then evidence should be pursued relentlessly to establish a diagnosis.     

Disseminated cryptococcosis presenting as palpable purpura.

Disseminated cryptococcosis with palpable purpura as the initial clinical manifestation developed in a patient with diffuse histiocytic lymphoma. Cryptococcal vascular injury in a thrombocytopenic cancer patient best explains this previously unreported presentation of cryptococcosis. Purpuric presentations of disseminated fungal infection are likely to increase in frequency as cancer therapy becomes more aggressive.     

Disseminated macronodular cutaneous candidiasis in chronic alcoholism

Disseminated candidiasis usually occurs in profoundly immunocompromised hosts. We described a case of disseminated macronodular cutaneous candidiasis in a man with no known risk for immunosuppression other than alcoholic liver disease and a second case of multiple macronodular cutaneous abscesses in an alcoholic man who had no evidence of systemic dissemination. One patient had testicular candidiasis, a previously unreported site of infection in disseminated candidiasis. Tests showed neutrophil and lymphocyte function to be normal; however, a marked defect in serum opsonization was demonstrated in one patient. It is postulated that chronic alcoholism with alcoholic liver disease resulted in impaired serum opsonization, which, in turn, predisposed these patients to candidal infection.     

Deep fungal infection in systemic lupus erythematosus - three cases reported, literature reviewed.

Three patients with systemic lupus erythematosus (SLE) and deep fungal infection are described. Two patients had disseminated cryptococcal infection and the third disseminated histoplasmosis. Allwere receiving corticosteroids at the time fungal infection developed. One patient with disseminated cryptococcosis improved after treatment with amphotericin B and 5-fluorocytosine. The other patient with disseminated cryptococcosis died before adequate therapy could be given. The patient with histoplasmosis responded satisfactorily to amphotericin B. A survey of the literature revealed 30 additional cases of deep fungal infection in patients with SLE, most of whom were on corticosteroid therapy. The majority of the patients had candidiasis (14 patients); 11 patients had severe cryptococcal infection. Other fungal infections reported were histoplasmosis, aspergillois, coccidioidomycosis, and maduromycosis caused by Allerscheria boydii. Twenty-seven patients died; in 22 death was related to the fungal infection. The fungal infection was not diagnosed until necropsy in at least 11 persons. Deep fungal infections should be considered whenever patients with SLE have fever of unknown origin, diffuse pulmonary infiltrates, or unexplained CNS symptoms.     

Immunodiagnosis of systemic candidiasis: mannan antigenemia detected by radioimmunoassay in experimental and human infections.

A radioimmunoassay (RIA) that detects candida mannan was developed so that immunodiagnosis of systemic candidiasis could be improved. The RIA was evaluated in an animal model of disseminated disease and in a panel of patient sera. Mannan antigenemia was detected with the RIA in 52% of 29 rabbits with systemic candidasis, but not in 60 normal rabbits or 31 rabbits with systemic aspergillosis. In an evaluation of human sera, mannan antigenemia was detected in five of 11 patients with systemic candidiasis, one of three patients with invasive gastrointestinal candidiasis, and one patient with a sustained candidemia associated with an infected intravenous catheter. Mannan was not detected in sera from 11 patients with superficial candida infections, seven patients colonized with Candida, three patients with chronic mucocutaneous candidiasis, eight patients with other systemic mycoses, or 22 normal donors. This study demonstrates the utility of this RIA for early, specific immunodiagnosis of invasive candidiasis.     

Periprosthetic candidal infections following arthroplasty

Candidal infection after prosthetic arthroplasty has been reported in six previous cases, to which four cases are now added. Candida albicans was the offending organism in four patients, Candida parapsilosis in three, Candida tropicalis in two, and Candida (Torulopsis) glabrata in one. None of the 10 patients had evidence of disseminated candidiasis, and, except for the uniform presence of a prosthesis, other underlying factors that are generally associated with candidal infections were present in only three. Clinical features that distinguished periprosthetic from natural bone and joint infection included an older patient population, the usual lack of predisposing factors other than the prosthesis, and the absence of evidence of disseminated candidiasis. All patients were treated with removal of the prosthesis and antifungal therapy, consisting of amphotericin B alone (six patients) or combined with 5-fluorocytosine (three patients) or ketoconazole (one patient). Infection appeared to be cured in nine of the 10 patients, but the follow-up was less than 1 year in five cases. Replacement with a new prosthetic joint was attempted in only two cases and successful in only one. Direct inoculation of organisms during surgery or transient unrecognized candidemia may initiate periprosthetic infection, which might then be promoted by favorable local factors, both mechanical and molecular. The role of prosthetic materials, candidal adhesins, and human factors such as fibronectin in initiating these infections has yet to be characterized.