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Case 3: Vesicular Rash
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Patient Presentation
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History
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Physical Exam
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Laboratory Results
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Differential Diagnosis
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Conclusive Studies
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Diagnosis
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Discussion
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References
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Patient Presentation
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A 40-year-old woman presented with multiple scalp, cubital fossa, axillary, and distal forearm ulcers of 3 months' duration, along with depression and loss of appetite of 2 months' duration. A physical examination of the patient revealed a rash that was vesicular in nature and itchy. Scratching caused the rash to blister, and ulcers eventually formed. The patient applied topical penicillin ointment to the ulcers. A home-based caregiver later reviewed her treatment history and changed the medication to penicillin powders, to no avail. Subsequently, the patient's appetite became poor and she became bedridden. She is a widow with 2 children, is currently unemployed, does not smoke or drink alcohol, and is neither a known hypertensive nor a diabetic patient.

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History
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The patient was screened for HIV and confirmed positive 2 years ago, after her spouse died of an undetermined illness. She started receiving antiretroviral therapy (ART) in January 2005. Her regimen consisted of nevirapine 200 mg twice daily, lamivudine 150 mg twice daily, and stavudine 30 mg twice daily. Her baseline CD4 count in January 2005 was 58 cells/µL. Subsequent results were 49 cells/µL in February 2005 and 40 cells/µL in January 2006. She reportedly had good adherence to her ART regimen.

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Physical Exam
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The initial physical examination revealed a chronically ill patient, bedridden with multiple skin ulcers on her head and other areas of the body. The lesions were deep (about 1 cm) and punctuated with undermined edges and superficial sloughs.

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Laboratory Results
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The results of initial investigations showed a packed cell volume of 17%, erythrocyte sedimentation rate of 170 mm/hour (Westergren method), total leukocyte count of 3.9 x 109/L, and total lymphocyte count of 624 x 109/L with differential of 74% neutrophils, 16% lymphocytes, and 10% monocytes. The blood film showed normocytic hypochromic red blood cells, adequate platelets, leukopenia, and band forms.

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Differential Diagnosis
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Multiple skin lesions in an HIV infection and disease of exfoiliative dermatitis in a patient with AIDS (World Health Organization [WHO] clinical Stage 4, bedridden >50% of days in the past month, wasting syndrome, and severe anemia).

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Conclusive Studies
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The wound culture analysis isolated Staphylococcus aureus that was sensitive to ofloxacin, clindamycin, ciprofloxacin, and erythromycin but resistant to ampicillin/cloxacillin (Ampiclox).

Because of the extensive nature of the patient's lesions and her marked immunocompromised state, the broad-spectrum antibiotics initially used to treat the suspected S aureus included intravenous metronidazole, intravenous gentamicin, intravenous cloxacillin, and oral fluconazole. These medications were changed, however, to oral ofloxacin and fluconazole after results from the sensitivity report were obtained. Multivitamins were added to the treatment regimen. The patient also received a unit of fresh whole blood and wound debridement.

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Diagnosis
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S aureus skin infection in a patient with AIDS (WHO clinical Stage 4 disease with wasting, anemia, and depression).

The patient's improvement was marginal in the first week, but after the debridement, change of intravenous antibiotics, and blood transfusion, her improvement became rapid. She had psychological support from medical team personnel who paid multiple visits to her and from church members who took turns cooking for her. Her appetite is now very good. Boils are breaking spontaneously and releasing pus. Debrided wounds are clean and granulating well.

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Discussion
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  • Home-based care is inadequate for treating S aureus skin infections. Hospital care is needed, including surgical debridement and daily dressing of wounds. Intravenous antibiotics rather than topical antibiotics should be used for patients such as this one who are severely immunocompromised and have CD4 counts of <60 cells/µL. Staphylococcal skin infection is the one of the most common causes of bacteremia in HIV-infected patients and it is associated with a high mortality rate.(1) S aureus is often resistant to common antibiotics such as penicillin and methicillin.(2,3) There is a high recurrence rate of infection when multidrug resistance is present.(1)

  • Even though their HIV infection is a chronic condition, immunocompromised patients should be discouraged from self-medication, witnessed with the use of penicillin ointment in this case, as most organisms causing skin infection are resistant to common antibiotics and the risk of systemic dissemination from skin infection is high in the absence of systemic antibiotic treatment.(3) Furthermore, home-based care providers should know their limits as well. The home-based care provider in this case should have sought a doctor or nurse on the team to diagnose the patient rather than recommend the use of penicillin powder. Appropriate care would have come earlier and complications would have been less severe.

  • Poor improvement despite good adherence to drugs can result from a number of factors: Interruption of the drug supply increases the potential for development of resistant HIV.(4) Sometimes, patients do not admit previous exposure to antiretroviral drugs (eg, a previous single-dose exposure). Also, drug resistance can develop without previous exposure to antiretrovirals, especially from unprotected sexual intercourse with spouses who take antiretrovirals in secret (and with poor adherence), thus transmitting HIV drug-resistant strains.(5,6) Therefore, condom use is needed even if both spouses are receiving antiretroviral drugs, except for special considerations of conception. Phenotypic/genotypic assays and other tests such as viral load measurements that could assist in making clinical decisions about ART are not available in many resource-limited countries.

  • Proper counseling is necessary and it serves to encourage spouses to disclose HIV status to each other. In this case, the patient's spouse died of an undetermined illness that most likely was AIDS associated, possibly adhered poorly to his medication regimen, and probably infected the patient with a drug-resistant strain of HIV.

  • The team approach to caregiving is a model for ensuring continuum of care. At Faith Alive Hospital in Jos, Nigeria, patients are seen on a regular basis by the same medical team consisting of a doctor, nurse, counselor, adherence counselor, treatment support specialist (a health worker who is HIV positive and has been receiving ART for at least 6 months), home-based care worker, and pharmacy technician. In this case, the home-based care worker was particularly helpful.

  • Good history taking and physical examination are vital tools for disease staging in resource-poor countries, especially in areas where adequate CD4 monitoring and viral load testing are not feasible. In the absence of laboratory tools for assessing the degree of HIV-induced immunodeficiency and the need for ART, greater reliance must be placed on the clinical presentation of the patient as a guide in deciding when to initiate treatment and when to change therapy. However, a lack of CD4 and viral load monitoring should not deter the use of ART. As demonstrated with the patient in this case, some readily available laboratory studies, such as hemoglobin testing to detect anemia, can be strong indicators of HIV-related morbidity and mortality.(7,8) Also, there is a strong correlation between CD4 count and total lymphocyte count, which can be conducted easily in clinical settings.(9-12)

Basic laboratory procedures remain necessary in resource-poor countries. Polypharmacy in the absence of test results is not the best option. Microbiological investigation of culture showed that the isolated staphylococcal organism was resistant to commonly used antibiotics. Antibiotic treatment with newer generation agents is more effective following resistance to conventional antibiotics, but laboratory confirmation of resistance often is not available.(2,3) In this case, surgical intervention using debridement and intravenous antibiotics were very helpful. Fresh screened blood with adequate nutrition also assisted recovery. Caution should be used in the process of administering blood, even if enzyme-linked immunosorbent assay (ELISA) or rapid HIV testing is performed, because it is possible for an HIV-infected individual to donate blood during the "window period" between the time of infection and the development of detectible antibodies.(13,14)

  • Skin presentations among HIV/AIDS patients are common, and early diagnosis and good management are key factors for improvement.(1-3)

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References

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1.   Kreisel K, Boyd K, Langenberg P, Roghmann MC. Risk factors for recurrence in patients with Staphylococcus aureus infections complicated by bacteremia. Diagn Microbiol Infect Dis. 2006 Jul;55(3):179-84. Epub 2006 May 2.
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2.   Elston DM. Optimal antibacterial treatment of uncomplicated skin and skin structure infections: applying a novel treatment algorithm. J Drugs Dermatol. 2005 Nov-Dec;4(6 Suppl):s15-9. Review.
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3.   Senthilkumar A, Kumar S, Sheagren JN. Increased incidence of Staphylococcus aureus bacteremia in hospitalized patients with acquired immunodeficiency syndrome. Clin Infect Dis. 2001 Oct 15;33(8):1412-6. Epub 2001 Sep 17.
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4.   Iliyasu Z, Kabir M, Abubakar IS, Babashani M, Zubair ZA. Compliance to antiretroviral therapy among AIDS patients in Aminu Kano Teaching Hospital, Kano, Nigeria. Niger J Med. 2005 Jul-Sep;14(3):290-4.
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5.   Turner D, Wainberg MA. HIV transmission and primary drug resistance. AIDS Rev. 2006 Jan-Mar;8(1):17-23. Review.
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6.   Shet A, Berry L, Mohri H, Mehandru S, Chung C, Kim A, Jean-Pierre P, Hogan C, Simon V, Boden D, Markowitz M. Tracking the prevalence of transmitted antiretroviral drug-resistant HIV-1: a decade of experience. J Acquir Immune Defic Syndr. 2006 Apr 1;41(4):439-46.
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7.   Ujah IA, Aisien OA, Mutihir JT, Vanderjagt DJ, Glew RH, Uguru VE. Factors contributing to maternal mortality in north-central Nigeria: a seventeen-year review. Afr J Reprod Health. 2005 Dec;9(3):27-40.
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8.   O'Brien ME, Kupka R, Msamanga GI, Saathoff E, Hunter DJ, Fawzi WW. Anemia is an independent predictor of mortality and immunologic progression of disease among women with HIV in Tanzania. J Acquir Immune Defic Syndr. 2005 Oct 1;40(2):219-25.
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9.   Mbanya D, Assah F, Ndembi N, Kaptue L. Monitoring antiretroviral therapy in HIV/AIDS patients in resource-limited settings: CD4 counts or total lymphocyte counts? Int J Infect Dis. 2006 Jun 6; [Epub ahead of print].
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10.   Erhabor O, Uko EK, Adias T. Absolute lymphocyte count as a marker for CD4 T-lymphocyte count: criterion for initiating antiretroviral therapy in HIV infected Nigerians. Niger J Med. 2006 Jan-Mar;15(1):56-9.
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11.   van der Ryst E, Kotze M, Joubert G, Steyn M, Pieters H, van der Westhuizen M, van Staden M, Venter C. Correlation among total lymphocyte count, absolute CD4<sup>+</sup> count, and CD4<sup>+</sup> percentage in a group of HIV-1-infected South African patients. J Acquir Immune Defic Syndr Hum Retrovirol. 1998 Nov 1;19(3):238-44.
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12.   Spacek LA, Griswold M, Quinn TC, Moore RD. Total lymphocyte count and hemoglobin combined in an algorithm to initiate the use of highly active antiretroviral therapy in resource-limited settings. AIDS. 2003 Jun 13;17(9):1311-7.
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13.   Heyns Adu P, Benjamin RJ, Swanevelder JP, Laycock ME, Pappalardo BL, Crookes RL, Wright DJ, Busch MP. Prevalence of HIV-1 in blood donations following implementation of a structured blood safety policy in South Africa. JAMA. 2006 Feb 1;295(5):519-26.
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14.   Fang CT, Field SP, Busch MP, Heyns Adu P. Human immunodeficiency virus-1 and hepatitis C virus RNA among South African blood donors: estimation of residual transfusion risk and yield of nucleic acid testing. Vox Sang. 2003 Jul;85(1):9-19.
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