A febrile boy with multiple papular skin lesions

Virat Sirisanthana M.D.,
Patient: An 8-year-old boy, Address: Chiang Mai
CC : High intermittent fever for 4 weeks and papular skin lesions for 2 weeks
PI:
> 4 weeks PTA, he developed a subacute onset of high-graded intermittent fever and mild cough.
> 2 weeks PTA, while fever persisted, papular lesions gradually appeared on his face. The lesions were not painful nor iching. Other than poor appetite, he has had no other symptom.
Past History:
He was the only child in the family. His parents died several years ago with "AIDS". He has been living with his uncle's family since then. He had never been sick. He was doing well at school. His immunization status was up to date.
Physical examination:

VS: T 40.5 C, pulse rate120/min, RR 28/minm, BP=100/60 mmHg., BW 21.5 Kg (weight is at 25-50%tile, W/A=89%, H/A=94%)
GA: appeared acutely ill and pale, but fully concious
Skin: multiple papular lesions at the face,extremities, perinial area. The lesions varied from 2 mm. to 7 mm. in diameter. Some had central necrosis. The lesions were more on the face and were not tender. (fig 1, 2). Old scars of the pruritic purpura eruption at the extremities (fig 3,4).
Figure 1
Figure 2

Figure 3
Figure 4

Lymph nodes: he had genralized lymphadenopathy (size 0.5-1 cm., non-tender and movable)
Eyes, ENT: mild pale conjunctiva, no oral thrush
Chest: Heart sound: WNL, Lungs: clear
Abdomen: palpable liver 1.5 cm below right costal margin, spleen was not palpable
NS: WNL

Active Problem list:
  1. Prolonged high intermittent fever for 4 weeks
2. Multiple papular skin lesions
3. Generalized lymphadenopathy and hepatomegaly
4. History of parents' death from "AIDS"
Initial laboratory investigations:
  CBC: Hb 9.3 g/dl, Hct 28 %, WBC=4,400/cu.mm (N 79%, L 15%, Mono 5%, E1%), platelets 156,000/cu.mm
PBS: RBC: hypochromic microcytic
U/A: WNL
HIV-Ab testing: positive
Direct Microscopy of a Wright stained touch smear of a nicking of the lesion at his face demonstrated the presence of yeast-like cells with a central septa (arrow), either within histiocytes or scattered inthe smear specimen. The yeast-cells were spherical to ellipsoidal, 2 to 6 um in diameter, and divided by fission. (Fig 5, 6)
Figure 5. X400
Figure 6. X1000
Course in the hospital
1.

The finding of typical yeast-like cells in the skin touch smear leaded the provisional diagnosis of Penicillium marneffei infection in this HIV-infected boy. He was given IV amphotericin B for 2 weeks, then followed by itraconazole 10 mg/kg/day orally. The fever gradually subsided in 7 days after initiation of amphotericin B. His skin lesions gradually dissapeared in 10 days. He was discharged home with itraconazole 10 mg/kg/day orally b.i.d to finish 10-week course of itraconazole therapy. We plan for him to receive secondary prophylaxis with itraconazole 5 mg/kg/day once daily for the rest of his life or until his CD4 count was sustained above 200 cells/cu.mm. for 6 months.
2.
He was given ferrous sulfate for the iron deficiency anemia.
3.
 Because of his HIV-infected status (Clinical category C), he was started on Pneumocystis carinii prophylaxsis with oral cotrimoxazole.
Other laboratory investigations :
 

> Skin touch specimen culture: positive for Penicillium marneffei
> Hemoculture X 2: positive for Penicillium marneffei
> CXR: WNL
Follow-up:
 

Three months after the discharge his body weight was 24kg (gained 2.5 kg). The liver was not palpable and his generalized lymphadenopathy disappeared. The CBC: Hb 11g/dl, Hct 33 %, WBC=3,700/cu.mm (N 54%, L 24%, Mono 10%, E12%), platelets 147,000/cu.mm.
Final Diagnosis : Penicillium marneffei infection in HIV-infected boy
 

Penicillium marneffei infection in patients with AIDS
by... Thira Sirisanthana
Emerg Infect Dis. 2001;7(3 Suppl):561

Penicillium marneffei infection (PM) is an important disease among HIV-infected persons in Southeast Asia. Discovered in 1956 from the bamboo rat, Rhizomys sinensis, in Vietnam, PM was first identified in HIV-infected persons in 1988. The disease has now been reported among HIV-infected persons in Thailand, Myanmar (Burma), Vietnam, Cambodia, Malaysia, northeastern India, Hong Kong, Taiwan, and southern China. Cases of PM also have been reported among HIV-infected persons from the United States, the United Kingdom, The Netherlands, Italy, France, Germany, Switzerland, Sweden, Australia, and Japan after they visited the PM-endemic region.

PM occurs late in the course of HIV infection. Our study found that the CD4+ cell count at the time of the diagnosis of PM was consistently less than 50 cells/ml. Clinical presentation included fever (in 99% of the patients), anemia (78%), pronounced weight loss (76%), generalized lymphadenopathy (58%), and hepatomegaly (51%). However, these conditions were not specific for PM and could be caused by HIV or other HIV-related opportunistic infections. A more specific finding was skin lesions, most commonly papules with central necrotic umbilication, which were seen in 71% of the patients.

In 63% of the patients with PM, a presumptive diagnosis could be made several days before the results of fungal culture were available. This was done by microscopic examination of a Wright-stained sample of bone marrow aspirate, touch smears of a skin biopsy specimen, or a lymph node biopsy specimen. It was easy to culture P. marneffei from various clinical specimens. Bone marrow culture was the most sensitive (100%), followed by culture of the specimen obtained from skin biopsy (90%) and blood culture (76%).

The fungus was sensitive to amphotericin B, itraconazole, and ketoconazole. The current recommended treatment regimen is to give amphotericin B, 0.6 mg/kg/day for 2 weeks, followed by itraconazole, 400 mg/day orally in two divided doses for the next 10 weeks. After initial treatment, the patient should be given itraconazole, 200 mg/day, as secondary prophylaxis for life.

P. marneffei has been isolated from several species of bamboo rats in the disease-endemic area, but epidemiologic studies have thus far failed to define an environmental exposure associated with the disease.

References and suggested further readings
1. Sirisanthana T. Penicillium marneffei infection in patients with AIDS. Emerg Infect Dis. 2001;7(3 Suppl):561.click for a pdf file
2. Vanittanakom N and T. Sirisanthana. Penicillium marmeffei infection in patients infected with Human Immunodeficiency Virus. Current Topics in Medical Mycology 1997;8:35-42.
3. Sirisanthana V, Sirisanthana T. Diseminated Penicillium marneffei infection in HIV-infected children Pediatr Infect Dis J 1995;14:935-940.
4. Sirisanthana V. Penicillium marneffei infection in AIDS children. (In Thai) click to read (intranet use only)

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