Patient Presentation
A 33-year-old transgendered male to female presented to the emergency department for evaluation of “multiple growths” on her face, fever and chills. Her eruption was presumed to be “chicken pox” as she had been exposed to varicella a few weeks prior. She was treated with valacyclovir and ciprofloxacin for 1 week with no improvement. Her past medical history includes HIV with no treatment for the past 3 years. Her CD4 count was 11/mm.3
On physical examination, there were numerous pink and some flesh-colored umbilicated papules. The size of the papules ranged between 5 mm to up to 10 mm, with central excoriations and hemorrhagic crusting, localized mostly to the central face and upper cutaneous lip. There were few healed papules on the chest. A Tzanck test and skin biopsy for H&E were performed.
What Is Your Diagnosis?
Diagnosis:
Disseminated Cryptococcus Neoformans
In 1895, Bushcke described the first Cryptococcus infection.1 In 1914, Verse reported and described central nervous system (CNS) involvement of this pathogen. Several decades later, the immuno-pathogenesis of cryptococcal infections was delineated. It was demonstrated that the lack of a granulomatous reaction causes symptomatic or disseminated disease as in the immunocompromised population.2
Cryptococcus is a systemic infection that affects mostly immunocompromised patients, including those infected with the human immunodeficiency virus (HIV), those with malignancy, renal failure, sarcoidosis, tuberculosis, severe diabetes mellitus, and organ transplant patients.3,4 It manifests mostly as a pulmonary infection, with primary cutaneous and CNS accounting for 15% to 20% of disseminated infections. Cryptococcus neoformans is widely dispersed worldwide, with serotypes A and D being the most common, and serotypes B and C being more common in tropical and subtropical regions.4,5 There is no correlation to age, gender, or race, although occupational exposure in laboratory workers has been reported.4
CLINICAL FEATURES
Primary pulmonary Cryptococcus varies from mild to severe. In mild cases, cough and fever may not be present, while in severe cases, pulmonary involvement may be potentially fatal. Pulmonary disease varies between dyspnea and cough to acute respiratory distress syndrome.4 Central nervous system involvement manifests as severe headaches, altered mental status, nausea and vomiting, among other neurological symptoms.3
Disseminated Cryptococcus could affect several systems, such as hepatic, reticuloendothelial, gastrointestinal, and integumentary.4
In cutaneous involvement, the head and neck are most commonly affected. Cutaneous presentation is polymorphic including umbilicated papules (molluscum contagiosum-like), pustules, vesicles, abscesses, blisters, subcutaneous nodules, granulomas, acneiform, small tumors, oral or cutaneous ulcers, or palatal discoloration.5 Patients with HIV generally present with molluscum-like papules. Cutaneous involvement through primary skin inoculation is extremely rare, and cutaneous disease almost always presents in the setting of disseminated infection. In immunocompetent patients, the skin eruption manifests as a single lesion, whereas in immunocompromised hosts, the eruption is usually more generalized.3,4
PATHOGENESIS
Cryptococcus neoformans is the causative agent of Cryptococcus infection. It is an encapsulated yeast that is zoophilic and anthropophilic. It is acquired by inhalation of the encapsulated budding yeast, which is ubiquitous. It is found in the soil, dust, and pigeon droppings, with no particular regional predisposition. Since the organism is encapsulated, the capsule is easily recognized on hematoxylin and eosin (H&E) sections. Staining with mucicarmine, methylene blue or alcian blue has been used to identify the capsule.3,4
Rapid Diagnosis of Cryptococcus Neoformans with a Tzanck Preparation
A Tzanck preparation can reliably and rapidly diagnose Cryptococcus. It is a direct, simple and inexpensive test. When performed on cryptococcal lesions, a Tzanck test shows narrow-based budding, encapsulated pleomorphic yeast.6 This is typical and diagnostic of Cryptococcus neoformans and was seen in our patient.
This Tzanck preparation is similar to the one used to diagnose herpes viruses, and it is usually positive in 50% to 79% of patients with herpes infection. In our patient, the serous discharge from one of the umbilicated papules was scraped and smeared on a slide and stained with Wright’s stain. (See Figure 2).
DIAGNOSIS AND TREATMENT
As stated above, Cryptococcus lesions appear classically as molluscum-like. The differential diagnosis of molluscum-like lesions includes histoplasmosis, molluscum contagiosum, basal cell carcinoma, secondary syphilis, among other opportunistic infections.3,4
In an immunocompromised patient, a high index of suspicion for fungal opportunistic culprits is essential. A skin biopsy and skin culture are diagnostic of cutaneous involvement.3,4,6 On skin biopsy, as was seen in our patient’s skin biopsy (Figure 3), the dermis is filled with numerous narrow-budding encapsulated yeast. Examination at 25°C on Sabouraud dextrose agar shows cream-to-beige and mucoid colonies due to the capsule surrounding the yeast cells.
Evaluation for disseminated disease is essential if the immunosuppressed host is affected. This includes serological testing for serum cryptococcal antigen, blood and urine cultures, chest radiographs, and lumbar puncture if CNS involvement is suspected.6,7,8 In our patient, a chest X-ray and CT scan of the chest showed mediastinal lymphadenopathy but no infiltrates, and a brain MRI did not show cryptococcal lesions. Blood cultures grew Cryptococcus.
In HIV patients without CNS disease, treatment consists of oral fluconazole of 400 mg to 800 mg daily, for up to 6 months. Alternatively, itraconazole 200 mg to 400 mg daily for 6 to 12 months can be used.4,6,7,8
If CNS is involved, intravenous amphotericin B at a dose of 0.5 to 1 mg/kg/day for 6 to 10 weeks is used, followed with fluconazole orally.4,6,7,8
In our patient, fluconazole 400 mg daily was started and continued at 14 months follow-up.
Her skin lesions improved gradually. She continues to improved, and was restarted on HAART therapy, as she had discontinued any AIDS treatment at her initial presentation due to financial reasons.
Catching this condition is critical
Cryptococcus is an opportunistic infection that is transmitted by direct inhalation of the yeast Cryptococcus neoformans. The population that is most susceptible to this infection is the immunocompromised. Therefore, a high index of suspicion and a rapid diagnostic test are essential in preventing the mortality that is associated with this infection. If untreated, Cryptococcus carries a mortality rate as high as 70%.6 In our patient, a Tzanck preparation was essential in making a rapid diagnosis of a potentially fatal infection in an immunocompromised host. Therefore, within hours of presenting to the emergency department, the diagnosis was made and treatment was initiated.
This case illustrates the importance of the Tzanck test as a rapid diagnostic tool for disseminated Cryptococcus. Undiagnosed hence untreated disseminated Cryptococcus is potentially fatal.
Patient Presentation
A 33-year-old transgendered male to female presented to the emergency department for evaluation of “multiple growths” on her face, fever and chills. Her eruption was presumed to be “chicken pox” as she had been exposed to varicella a few weeks prior. She was treated with valacyclovir and ciprofloxacin for 1 week with no improvement. Her past medical history includes HIV with no treatment for the past 3 years. Her CD4 count was 11/mm.3
On physical examination, there were numerous pink and some flesh-colored umbilicated papules. The size of the papules ranged between 5 mm to up to 10 mm, with central excoriations and hemorrhagic crusting, localized mostly to the central face and upper cutaneous lip. There were few healed papules on the chest. A Tzanck test and skin biopsy for H&E were performed.
What Is Your Diagnosis?
Diagnosis:
Disseminated Cryptococcus Neoformans
In 1895, Bushcke described the first Cryptococcus infection.1 In 1914, Verse reported and described central nervous system (CNS) involvement of this pathogen. Several decades later, the immuno-pathogenesis of cryptococcal infections was delineated. It was demonstrated that the lack of a granulomatous reaction causes symptomatic or disseminated disease as in the immunocompromised population.2
Cryptococcus is a systemic infection that affects mostly immunocompromised patients, including those infected with the human immunodeficiency virus (HIV), those with malignancy, renal failure, sarcoidosis, tuberculosis, severe diabetes mellitus, and organ transplant patients.3,4 It manifests mostly as a pulmonary infection, with primary cutaneous and CNS accounting for 15% to 20% of disseminated infections. Cryptococcus neoformans is widely dispersed worldwide, with serotypes A and D being the most common, and serotypes B and C being more common in tropical and subtropical regions.4,5 There is no correlation to age, gender, or race, although occupational exposure in laboratory workers has been reported.4
CLINICAL FEATURES
Primary pulmonary Cryptococcus varies from mild to severe. In mild cases, cough and fever may not be present, while in severe cases, pulmonary involvement may be potentially fatal. Pulmonary disease varies between dyspnea and cough to acute respiratory distress syndrome.4 Central nervous system involvement manifests as severe headaches, altered mental status, nausea and vomiting, among other neurological symptoms.3
Disseminated Cryptococcus could affect several systems, such as hepatic, reticuloendothelial, gastrointestinal, and integumentary.4
In cutaneous involvement, the head and neck are most commonly affected. Cutaneous presentation is polymorphic including umbilicated papules (molluscum contagiosum-like), pustules, vesicles, abscesses, blisters, subcutaneous nodules, granulomas, acneiform, small tumors, oral or cutaneous ulcers, or palatal discoloration.5 Patients with HIV generally present with molluscum-like papules. Cutaneous involvement through primary skin inoculation is extremely rare, and cutaneous disease almost always presents in the setting of disseminated infection. In immunocompetent patients, the skin eruption manifests as a single lesion, whereas in immunocompromised hosts, the eruption is usually more generalized.3,4
PATHOGENESIS
Cryptococcus neoformans is the causative agent of Cryptococcus infection. It is an encapsulated yeast that is zoophilic and anthropophilic. It is acquired by inhalation of the encapsulated budding yeast, which is ubiquitous. It is found in the soil, dust, and pigeon droppings, with no particular regional predisposition. Since the organism is encapsulated, the capsule is easily recognized on hematoxylin and eosin (H&E) sections. Staining with mucicarmine, methylene blue or alcian blue has been used to identify the capsule.3,4
Rapid Diagnosis of Cryptococcus Neoformans with a Tzanck Preparation
A Tzanck preparation can reliably and rapidly diagnose Cryptococcus. It is a direct, simple and inexpensive test. When performed on cryptococcal lesions, a Tzanck test shows narrow-based budding, encapsulated pleomorphic yeast.6 This is typical and diagnostic of Cryptococcus neoformans and was seen in our patient.
This Tzanck preparation is similar to the one used to diagnose herpes viruses, and it is usually positive in 50% to 79% of patients with herpes infection. In our patient, the serous discharge from one of the umbilicated papules was scraped and smeared on a slide and stained with Wright’s stain. (See Figure 2).
DIAGNOSIS AND TREATMENT
As stated above, Cryptococcus lesions appear classically as molluscum-like. The differential diagnosis of molluscum-like lesions includes histoplasmosis, molluscum contagiosum, basal cell carcinoma, secondary syphilis, among other opportunistic infections.3,4
In an immunocompromised patient, a high index of suspicion for fungal opportunistic culprits is essential. A skin biopsy and skin culture are diagnostic of cutaneous involvement.3,4,6 On skin biopsy, as was seen in our patient’s skin biopsy (Figure 3), the dermis is filled with numerous narrow-budding encapsulated yeast. Examination at 25°C on Sabouraud dextrose agar shows cream-to-beige and mucoid colonies due to the capsule surrounding the yeast cells.
Evaluation for disseminated disease is essential if the immunosuppressed host is affected. This includes serological testing for serum cryptococcal antigen, blood and urine cultures, chest radiographs, and lumbar puncture if CNS involvement is suspected.6,7,8 In our patient, a chest X-ray and CT scan of the chest showed mediastinal lymphadenopathy but no infiltrates, and a brain MRI did not show cryptococcal lesions. Blood cultures grew Cryptococcus.
In HIV patients without CNS disease, treatment consists of oral fluconazole of 400 mg to 800 mg daily, for up to 6 months. Alternatively, itraconazole 200 mg to 400 mg daily for 6 to 12 months can be used.4,6,7,8
If CNS is involved, intravenous amphotericin B at a dose of 0.5 to 1 mg/kg/day for 6 to 10 weeks is used, followed with fluconazole orally.4,6,7,8
In our patient, fluconazole 400 mg daily was started and continued at 14 months follow-up.
Her skin lesions improved gradually. She continues to improved, and was restarted on HAART therapy, as she had discontinued any AIDS treatment at her initial presentation due to financial reasons.
Catching this condition is critical
Cryptococcus is an opportunistic infection that is transmitted by direct inhalation of the yeast Cryptococcus neoformans. The population that is most susceptible to this infection is the immunocompromised. Therefore, a high index of suspicion and a rapid diagnostic test are essential in preventing the mortality that is associated with this infection. If untreated, Cryptococcus carries a mortality rate as high as 70%.6 In our patient, a Tzanck preparation was essential in making a rapid diagnosis of a potentially fatal infection in an immunocompromised host. Therefore, within hours of presenting to the emergency department, the diagnosis was made and treatment was initiated.
This case illustrates the importance of the Tzanck test as a rapid diagnostic tool for disseminated Cryptococcus. Undiagnosed hence untreated disseminated Cryptococcus is potentially fatal.
Patient Presentation
A 33-year-old transgendered male to female presented to the emergency department for evaluation of “multiple growths” on her face, fever and chills. Her eruption was presumed to be “chicken pox” as she had been exposed to varicella a few weeks prior. She was treated with valacyclovir and ciprofloxacin for 1 week with no improvement. Her past medical history includes HIV with no treatment for the past 3 years. Her CD4 count was 11/mm.3
On physical examination, there were numerous pink and some flesh-colored umbilicated papules. The size of the papules ranged between 5 mm to up to 10 mm, with central excoriations and hemorrhagic crusting, localized mostly to the central face and upper cutaneous lip. There were few healed papules on the chest. A Tzanck test and skin biopsy for H&E were performed.
What Is Your Diagnosis?
Diagnosis:
Disseminated Cryptococcus Neoformans
In 1895, Bushcke described the first Cryptococcus infection.1 In 1914, Verse reported and described central nervous system (CNS) involvement of this pathogen. Several decades later, the immuno-pathogenesis of cryptococcal infections was delineated. It was demonstrated that the lack of a granulomatous reaction causes symptomatic or disseminated disease as in the immunocompromised population.2
Cryptococcus is a systemic infection that affects mostly immunocompromised patients, including those infected with the human immunodeficiency virus (HIV), those with malignancy, renal failure, sarcoidosis, tuberculosis, severe diabetes mellitus, and organ transplant patients.3,4 It manifests mostly as a pulmonary infection, with primary cutaneous and CNS accounting for 15% to 20% of disseminated infections. Cryptococcus neoformans is widely dispersed worldwide, with serotypes A and D being the most common, and serotypes B and C being more common in tropical and subtropical regions.4,5 There is no correlation to age, gender, or race, although occupational exposure in laboratory workers has been reported.4
CLINICAL FEATURES
Primary pulmonary Cryptococcus varies from mild to severe. In mild cases, cough and fever may not be present, while in severe cases, pulmonary involvement may be potentially fatal. Pulmonary disease varies between dyspnea and cough to acute respiratory distress syndrome.4 Central nervous system involvement manifests as severe headaches, altered mental status, nausea and vomiting, among other neurological symptoms.3
Disseminated Cryptococcus could affect several systems, such as hepatic, reticuloendothelial, gastrointestinal, and integumentary.4
In cutaneous involvement, the head and neck are most commonly affected. Cutaneous presentation is polymorphic including umbilicated papules (molluscum contagiosum-like), pustules, vesicles, abscesses, blisters, subcutaneous nodules, granulomas, acneiform, small tumors, oral or cutaneous ulcers, or palatal discoloration.5 Patients with HIV generally present with molluscum-like papules. Cutaneous involvement through primary skin inoculation is extremely rare, and cutaneous disease almost always presents in the setting of disseminated infection. In immunocompetent patients, the skin eruption manifests as a single lesion, whereas in immunocompromised hosts, the eruption is usually more generalized.3,4
PATHOGENESIS
Cryptococcus neoformans is the causative agent of Cryptococcus infection. It is an encapsulated yeast that is zoophilic and anthropophilic. It is acquired by inhalation of the encapsulated budding yeast, which is ubiquitous. It is found in the soil, dust, and pigeon droppings, with no particular regional predisposition. Since the organism is encapsulated, the capsule is easily recognized on hematoxylin and eosin (H&E) sections. Staining with mucicarmine, methylene blue or alcian blue has been used to identify the capsule.3,4
Rapid Diagnosis of Cryptococcus Neoformans with a Tzanck Preparation
A Tzanck preparation can reliably and rapidly diagnose Cryptococcus. It is a direct, simple and inexpensive test. When performed on cryptococcal lesions, a Tzanck test shows narrow-based budding, encapsulated pleomorphic yeast.6 This is typical and diagnostic of Cryptococcus neoformans and was seen in our patient.
This Tzanck preparation is similar to the one used to diagnose herpes viruses, and it is usually positive in 50% to 79% of patients with herpes infection. In our patient, the serous discharge from one of the umbilicated papules was scraped and smeared on a slide and stained with Wright’s stain. (See Figure 2).
DIAGNOSIS AND TREATMENT
As stated above, Cryptococcus lesions appear classically as molluscum-like. The differential diagnosis of molluscum-like lesions includes histoplasmosis, molluscum contagiosum, basal cell carcinoma, secondary syphilis, among other opportunistic infections.3,4
In an immunocompromised patient, a high index of suspicion for fungal opportunistic culprits is essential. A skin biopsy and skin culture are diagnostic of cutaneous involvement.3,4,6 On skin biopsy, as was seen in our patient’s skin biopsy (Figure 3), the dermis is filled with numerous narrow-budding encapsulated yeast. Examination at 25°C on Sabouraud dextrose agar shows cream-to-beige and mucoid colonies due to the capsule surrounding the yeast cells.
Evaluation for disseminated disease is essential if the immunosuppressed host is affected. This includes serological testing for serum cryptococcal antigen, blood and urine cultures, chest radiographs, and lumbar puncture if CNS involvement is suspected.6,7,8 In our patient, a chest X-ray and CT scan of the chest showed mediastinal lymphadenopathy but no infiltrates, and a brain MRI did not show cryptococcal lesions. Blood cultures grew Cryptococcus.
In HIV patients without CNS disease, treatment consists of oral fluconazole of 400 mg to 800 mg daily, for up to 6 months. Alternatively, itraconazole 200 mg to 400 mg daily for 6 to 12 months can be used.4,6,7,8
If CNS is involved, intravenous amphotericin B at a dose of 0.5 to 1 mg/kg/day for 6 to 10 weeks is used, followed with fluconazole orally.4,6,7,8
In our patient, fluconazole 400 mg daily was started and continued at 14 months follow-up.
Her skin lesions improved gradually. She continues to improved, and was restarted on HAART therapy, as she had discontinued any AIDS treatment at her initial presentation due to financial reasons.
Catching this condition is critical
Cryptococcus is an opportunistic infection that is transmitted by direct inhalation of the yeast Cryptococcus neoformans. The population that is most susceptible to this infection is the immunocompromised. Therefore, a high index of suspicion and a rapid diagnostic test are essential in preventing the mortality that is associated with this infection. If untreated, Cryptococcus carries a mortality rate as high as 70%.6 In our patient, a Tzanck preparation was essential in making a rapid diagnosis of a potentially fatal infection in an immunocompromised host. Therefore, within hours of presenting to the emergency department, the diagnosis was made and treatment was initiated.
This case illustrates the importance of the Tzanck test as a rapid diagnostic tool for disseminated Cryptococcus. Undiagnosed hence untreated disseminated Cryptococcus is potentially fatal.
