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Case 2: Diffuse Rash
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Patient Presentation
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History
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Physical Exam
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Learning Points
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Discussion
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References
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Figures
Figure 1.Right lower extremity
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Figure 2.Close-up image of individual lesion on right extremity
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Patient Presentation
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A 32-year-old HIV-infected woman from Uganda with a recent CD4 count of 400 cells/µL presents with a diffuse, pruritic rash that has persisted for 3-4 years.

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History
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The patient was diagnosed with HIV infection approximately 3 1/2 years ago, and started taking a 3-drug regimen (zidovudine, lamivudine, abacavir) shortly thereafter. She has been on antiretroviral therapy (ART) for 3 years, with a good CD4 response (the nadir CD4 count was 40 cells/µL). The appearance of her rash predates the initiation of ART.

The rash has been present mostly on her arms and legs. It was extremely pruritic initially, though itching became less severe after she started taking ART. The patient considers the rash disfiguring. She has no other complaints and is taking her medications regularly, as indicated by appropriate pill counts at her clinic visits. She denies taking any new medications. No other members of her family have similar symptoms. She reports no unusual environmental exposures.

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Physical Exam
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General: Examination of the skin revealed multiple scattered hyperpigmented macules, some with central hypopigmentation, and rare papules, present from head to feet, but most prominently over both lower extremities. The distribution was not follicular. (See figures.)

Laboratory tests: None available, other than CD4 count.

Differential diagnosis: Possible causes of this presentation included pruritic papular eruption (PPE), prurigo nodularis, lichen simplex chronicus, eosinophilic folliculitis, drug eruption, and scabies.

Probable diagnosis: A diagnostic biopsy had not been performed. PPE with postinflammatory hyperpigmentation and scarring was diagnosed clinically.

Treatment: The patient was treated with topical corticosteroids for a course of indefinite duration. This is the standard of care at the HIV clinic where she receives treatment. She was not treated with any oral medications for this condition.

Clinical course: Unknown. The patient was examined only once, although her symptoms had improved marginally in recent years after she began receiving ART and topical steroids.

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Learning Points
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  • PPE is a common manifestation of HIV/AIDS, particularly in regions with a high prevalence of mosquitoes.

  • The prevalence of PPE and the severity of its symptoms are inversely proportional to absolute CD4 counts.

  • The underlying etiology of PPE appears to be an abnormal response to arthropod bites in susceptible individuals.

  • Topical steroids appear to be relatively ineffective. Other treatments (including ultraviolet B phototherapy and pentoxifylline) show promise, but are relatively unstudied.

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Discussion
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Although no diagnosis could be made on the basis of tissue biopsy, the skin findings for this patient are highly consistent with pruritic papular eruption (PPE) with postinflammatory hypo- and hyperpigmentation and scarring from prior lesions. Many patients at the clinic had similar symptoms and were treated symptomatically with topical steroids and calamine lotion. The effectiveness of this treatment has not been established.

PPE typically presents as scattered papules or pustules that are <1 cm in diameter and located primarily in the extremities and the trunk, often with superficial excoriation. PPE has been well described in sub-Saharan Africa and elsewhere, with varying geographical prevalence. Reported PPE prevalence among HIV-positive patients has ranged from 18% in hospitalized patients in Zaire (1) to 33-37% in Thailand (2,3) to 46% in Haiti,(4) with few reported cases in the United States, except in areas with high mosquito prevalence such as southern Florida,(5) where a PPE prevalence of 11% has been reported.(6)

An inverse relationship between the absolute CD4 cell count and the prevalence and symptom severity of PPE has been reported. Symptoms have been found more often in patients with advanced HIV disease.(7,8) A study of 120 HIV-positive patients in Thailand found 0 cases of PPE in those with CD4 counts of >500 cells/µL.(3) In contrast, 34% of patients with CD4 counts between 200 and 499 cells/µL, and 81% of patients with CD4 counts of <200 cells/µL, showed evidence of PPE.

The clinical presentation of PPE is well described, but the underlying etiology was somewhat elusive until recently. In a 2004 study of 102 HIV-positive patients in Uganda, a majority of biopsy specimens indicated that a histology of arthropod bites was highly consistent with the development of PPE papules.(9) Specifically, most of the specimens revealed "moderately dense to dense, superficial and deep, perivascular and interstitial infiltrates of lymphocytes and many eosinophils beneath an epidermis that was slightly hyperplastic," whereas others showed a "punctum," or focal area of epidermal spongiosis surrounded by dermal infiltrates. The investigators surmised that the occurrence of PPE could represent an abnormal and exaggerated immune response to mosquito bites in individuals with low CD4 counts.

At the clinic where this patient sought care, persistent pruritus in HIV-positive patients was routinely treated with topical steroids, even though this approach has been shown to be relatively ineffective.(10) One small study of 8 patients showed partial resolution of lesions with regular ultraviolet B phototherapy,(11) though this treatment remains controversial. Additionally, the use of pentoxifylline appears promising as an effective treatment,(12) but this approach has not been studied in a randomized controlled trial.

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References

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1.   Colebunders R, Mann JM, Francis H, Bila K, Izaley L, Kakonde N, Hood AF, Quinn TC, Gigase P, Van Marck E, et al. Generalized papular pruritic eruption in African patients with human immunodeficiency virus infection. Aids 1987; 1:117-21.
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2.   Sivayathorn A, Srihra B, Leesanguankul W. Prevalence of skin disease in patients infected with human immunodeficiency virus in Bangkok, Thailand. Ann Acad Med Singapore 1995; 24:528-33.
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3.   Wiwanitkit V. Prevalence of dermatological disorders in Thai HIV-infected patients correlated with different CD4 lymphocyte count statuses: a note on 120 cases. Int J Dermatol 2004; 43:265-8.
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4.   Liautaud B, Pape JW, DeHovitz JA, Thomas F, LaRoche AC, Verdier RI, Deschamps MM, Johnson WD. Pruritic skin lesions. A common initial presentation of acquired immunodeficiency syndrome. Arch Dermatol 1989; 125:629-32.
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5.   Hevia O, Jimenez-Acosta F, Ceballos PI, Gould EW, Penneys NS. Pruritic papular eruption of the acquired immunodeficiency syndrome: a clinicopathologic study. J Am Acad Dermatol 1991; 24:231-5.
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6.   Goldstein B, Berman B, Sukenik E, Frankel SJ. Correlation of skin disorders with CD4 lymphocyte counts in patients with HIV/AIDS. J Am Acad Dermatol 1997; 36:262-4.
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7.   Mignard M, Spira RM, Morlat P, Dabis F, Doutre MS. Correlation of skin disorders with CD4 lymphocyte counts in patients with HIV/AIDS. J Am Acad Dermatol 1998; 39:298-9.
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8.   Muhammad B, Eligius L, Mugusi F, Aris E, Chale S, Magao P, Josiah R, Moshi A, Swai A, Pallangyo N, Sandstrom E, Mhalu F, Biberfeld G, Pallangyo K. The prevalence and pattern of skin diseases in relation to CD4 counts among HIV-infected police officers in Dar es Salaam. Trop Doct 2003; 33:44-8.
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9.   Resneck JS, Jr., Van Beek M, Furmanski L, Oyugi J, LeBoit PE, Katabira E, Kambugu F, Maurer T, Berger T, Pletcher MJ, Machtinger EL. Etiology of pruritic papular eruption with HIV infection in Uganda. Jama 2004; 292:2614-21.
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10.  Habif T. Clinical Dermatology, 4th Edition. St. Louis: CV Mosby Co.; 2004.
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11.   Pardo RJ, Bogaert MA, Penneys NS, Byrne GE, Jr., Ruiz P. UVB phototherapy of the pruritic papular eruption of the acquired immunodeficiency syndrome. J Am Acad Dermatol 1992; 26:423-8.
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12.   Berman B, Flores F, Burke G, 3rd. Efficacy of pentoxifylline in the treatment of pruritic papular eruption of HIV-infected persons. J Am Acad Dermatol 1998; 38:955-9.
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