Skin Pathology Commonly Associated With HIV Infection
<p>Herpes zoster, or <i>shingles</i>, is a reactivation of a previous herpes varicella-zoster virus infection. It can be one of the earliest manifestations of HIV. A longitudinal study showed an incidence of 29.4 cases per 1000 person-years among people seropositive for HIV vs 2.0 cases per 1000 person-years among control participants who were seronegative for HIV.<sup>3</sup> Shingles risk and severity may be increased with increasing immunosuppression.<sup>4</sup></p> <p>Because shingles has a distinctive disease course and lesions, clinical diagnosis is usually accurate, but laboratory studies may be required for confirmation.<sup>5</sup> Patients often first experience pain along one of the sensory nerves of the skin, followed by a painful rash several days later.<sup>6</sup> The rash begins with grouped vesicles confined to 1 dermatome or spread over 2 adjacent dermatomes. The vesicles eventually crust over and then heal 3 to 4 weeks later, but may result in significant scarring. Pain sometimes persists after resolution of the vesiculation (ie, postherpetic neuralgia).</p>
<p>Seborrheic dermatitis, which is one of the most common skin manifestations of HIV, has been reported in 85% to 95% of people positive for HIV vs 3% to 5% of uninfected persons.<sup>7</sup> Its etiology remains unknown, but it most commonly manifests when CD4 counts drop to ≤550 cells/µL and worsens with CD4 count declines, making it a useful marker of disease progression.<sup>2,7</sup> Risk is also increased in men, individuals with oily skin, and in climates with cold, dry winter air.<sup>7</sup> Recurrences are common and stress can trigger a flare-up.<sup>8</sup></p> <p>Seborrheic dermatitis is characterized by itchy reddish or pink patches of skin with concomitant greasy-looking white or yellowish flakes or scales.<sup>8</sup> It typically affects the scalp and face, but may also involve the ears, chest, upper back, axillae, and groin.<sup>8</sup></p>
<p>Xerosis, or dry skin, is found in >20% of people with HIV.<sup>2</sup> It is thought to result from impaired skin barrier function of the stratum corneum.<sup>9</sup> Low CD4 counts and indinavir use in persons with higher CD4 cell counts have been associated with an increased risk for xerosis.<sup>10</sup> Because of the association between CD4 counts and xerosis, some clinicians have used the condition as a disease marker.<sup>2</sup></p> <p>Xerosis is characterized by dull, flaky/scaly, or rough skin, which usually affects the extremities.<sup>2</sup> Pruritus is also common, particularly when the forearms, hands, elbows, or lower extremities are affected.<sup>11</sup> Patients with pruritus are at increased risk for skin breaches and secondary bacterial infections, especially if they are prone to scratching.</p> <p><i>Photo Credit: Allan Harris.</i></p>
<p>Atopic dermatitis is a serious condition that has been reported to affect between 30% and 50% of people who are HIV positive vs ≤20% of those who are HIV negative.<sup>2</sup> The condition has been associated with elevated immunoglobulin E levels, eosinophilia, and possible Th1-Th2 imbalances.<sup>2,12</sup> Because nearly all patients with AIDS demonstrate Th1-Th2 imbalances, they are at particularly high risk for atopic dermatitis.<sup>2</sup></p> <p>Patients generally present with chronic, red, thick, lichenified plaques and severe, incessant pruritus that can have an impact on daily function and sleep and reduce quality of life significantly.<sup>13</sup> Isolated pruritic papules are sometimes observed. The hands, face, and eyelids, and areas of the body with large skin folds are most often affected; however, inflammatory flare-ups can affect the entire body and might necessitate hospitalization.<sup>13</sup></p>
<p>Eosinophilic folliculitis almost exclusively affects patients with HIV/AIDS, and its presence should raise suspicion of HIV infection or another immune disorder in undiagnosed patients. It is most commonly observed when CD4 counts drop to <300 cells/µL.<sup>14</sup> The condition has been associated with increased serum immunoglobulin E levels, eosinophilia, and peripheral leukocytosis.<sup>2</sup></p> <p>Eosinophilic folliculitis presents as recurrent patches of erythematous pustules and papules, with approximately 50% of patients experiencing pruritus.<sup>15</sup> The papules eventually become confluent, forming indurate polycyclic plaques that heal from the center outward before resolving, but often leaving behind hyperpigmentation and scaling.<sup>15</sup> The condition typically affects the face, neck, upper chest, and back, with areas below the nipple line rarely affected.<sup>2</sup></p> <p><i>Photo Credit: Biophoto Associates/Science Source.</i></p>
<p>Molluscum contagiosum occurs in approximately 5% to 18% of HIV-infected people, but is becoming rare in areas of the world with good access to highly effective antiretroviral therapies (HAART).<sup>16</sup> It is caused by an infection of the epidermal keratinocytes by the molluscum contagiosum virus, a double-stranded DNA virus belonging to the <i>Poxviridae</i> family.<sup>16,17</sup></p> <p>Patients present with small (≤5 mm in diameter), raised lesions that are usually white, pink, or flesh colored with a dimple or pit in the center.<sup>17</sup> The lesions are typically smooth, firm, and pearly appearing, and can affect any area of the body, although they are rarely found on the palms or soles. They may occur as solitary lesions or in groups and typically resolve within 6 to 12 months without any scarring.<sup>17</sup> Genital lesions may take longer to resolve, and healing times up to 4 years have been reported.<sup>16,17</sup></p> <p><i>Photo Credit: Medical Images RM/AL LAMME.</i></p>
<p>Photodermatitis is rare, occurring in approximately 5% of people who are HIV positive.<sup>18,19</sup> HAART and other medications, including nonsteroidal anti-inflammatory drugs and trimethoprim-sulfamethoxazole, can increase the risk for photosensitivity and subsequent photodermatitis. Risk is also increased in individuals with CD4 counts <50 cells/µL.<sup>18,19</sup></p> <p>Photodermatitis manifests on sun-exposed areas of the body, but can extend beyond these areas in patients with advanced disease.<sup>19</sup> Presentations can vary significantly and clinical findings may include polymorphic light eruption, actinic prurigo, chronic actinic dermatitis, porphyria cutanea tarda, photosensitive granuloma annulare, and lichenoid photoeruption.<sup>18</sup> In rare cases, skin depigmentation mimicking vitiligo may be observed.<sup>18</sup> Patients with darker skin, particularly those of African origin, are most commonly affected, even after controlling for CD4 counts and ultraviolet index.<sup>19</sup></p>
<p>Prurigo nodularis is the most common skin disorder in patients with HIV/AIDS in Africa, but it is uncommon in areas with good access to HAART.<sup>2</sup> Its etiology remains unknown, but bug bites have been found to be a triggering event, particularly in developing parts of the world.<sup>20,21</sup> Prurigo nodularis is most commonly observed in middle-aged and older persons, with 80% of affected individuals having a personal or family history of atopic dermatitis, asthma, or hay fever.<sup>20,21</sup> The condition most commonly manifests in people with CD4 counts <50 cells/µL.<sup>20</sup></p> <p>Patients typically present with discrete, scaly, firm, symmetric, hyperpigmented, or purpuric nodules or papules measuring no more than 20 mm in diameter.<sup>21</sup> The lesions are often severely pruritic, resulting in excessive scratching, and can occur as solitary lesions or number in the hundreds. They usually occur on the legs, trunk, and extensor surfaces of the arms.<sup>21</sup> On resolution, there may be residual hyperpigmentation and scarring.<sup>21</sup><p><p><i>Photo Credit: Biophoto Associates/Science Source.</i></p>
<p>The prevalence of psoriasis in people who are HIV positive is thought to be the same as that of the general population, but the condition might worsen or first be detected following HIV infection.<sup>2,22</sup> The development of HIV-associated psoriasis has been associated with a poor prognosis in untreated patients, particularly those with late-stage disease.<sup>22</sup> Patients with AIDS in whom severe exacerbations develop are at high risk for systemic infections, including <i>Staphylococcus aureus</i> superinfection.<sup>22</sup></p> <p>Psoriasis presentations vary in those with HIV and may be atypical.<sup>22</sup> Plaque and erythrodermic psoriasis are most common, but several morphologic types can coexist. Classic findings of plaque psoriasis include symmetric erythematous patches or plaques with silver scales. Erythrodermic psoriasis may manifest as desquamate large scales resembling lamellar ichthyosis or as a chronic erythrodermic drug eruption. Rupioid psoriasis and sebopsoriasis may also be present.<sup>22</sup></p>
<p>Kaposi sarcoma is a multifocal tumor that involves the skin and other organs.<sup>23</sup> It is the most common neoplasm in patients with AIDS, although its prevalence in this population has decreased significantly since the advent of HAART. Currently, approximately 2500 cases of Kaposi sarcoma occur annually in the United States, but these include people who are not HIV positive (eg, following organ transplant).<sup>24</sup></p> <p>Nearly all patients have cutaneous lesions.<sup>23,24</sup> These lesions are palpable, nonpruritic, and may have a macular, papular, nodular, or plaque-like appearance.<sup>24</sup> They range in size from several millimeters to several centimeters in diameter. On white or light skin, they appear red or purple, and on darker skin, they appear bluish, brown, or black. They are often distributed along Langer lines, most commonly on the head, neck, and lower extremities, although any area of the body can be affected.<sup>23</sup> Lesions are usually painless unless located in sensitive areas (eg, soles of the feet).</p> <p><i>Photo Credit: Science Source.</i></p>
Dermatologic problems affect >90% of patients with HIV infection at some point during their disease.1 The presence of certain skin conditions in undiagnosed patients, such as extensive herpes zoster infection and seborrheic dermatitis, may serve as indicators of HIV and can facilitate early diagnosis when properly recognized.1 Other conditions are associated with late-stage disease, such as Kaposi sarcoma, which was one of the first skin conditions linked with HIV/AIDS.2 Currently, >50 skin manifestations have been associated with HIV, including bacterial, fungal, and viral infections, inflammatory and eczematous eruptions, drug-related rashes, and skin tumors.2 Many of these disorders are painful and disfiguring, making prompt recognition essential to ensure timely treatment and preserve patient self-esteem and quality of life.
Compiled by Christina Loguidice
- Halder S, Banerjee S, Halder A, Pal PR. Skin diseases in HIV-infected patients: impact of immune status and histological correlation. Indian J Sex Transm Dis. 2012;33(1):65-67.
- Cedeno-Laurent F, Gómez-Flores M, Mendez N, et al. New insights into HIV-1-primary skin disorders. J Int AIDS Soc. 2011;14:5.
- Buchbinder SP, Katz MH, Hessol NA, et al. Herpes zoster and human immunodeficiency virus infection. J Infect Dis. 1992;166(5):1153-1156.
- Erlich KS. Varicella-Zoster Virus and HIV. HIV InSite. November 2011. Accessed October 17, 2017.
- Gnann JW Jr, Whitley RJ. Herpes zoster. N Engl J Med. 2002;347(5):340-346.
- Leppard B, Naburi AE. Herpes zoster: an early manifestation of HIV infection. Afr Health. 1998;21(1):5-6.
- Coffey S, ed. Seborrheic dermatitis. In: Guide for HIV/AIDS Clinical Care. Newark, NJ: AIDS Education & Training Center Program National Coordinating Resource Center; 2014. Accessed October 17, 2017.
- American Academy of Dermatology. Seborrheic dermatitis. Accessed October 17, 2017.
- Mischo M, von Kobyletzki LB, Bründermann E, et al. Similar appearance, different mechanisms: xerosis in HIV, atopic dermatitis and ageing. Exp Dermatol. 2014;23(6):446-448.
- Lee D, Benson CA, Lewis CE, Grunfeld C, Scherzer R. Prevalence and factors associated with dry skin in HIV infection: the FRAM study. AIDS (London, England). 2007;21(15):2051-2057.
- Terrie YC. Itchy scratchy skin: preventing and managing xerosis. Pharmacy Times. June 18, 2017. Accessed October 17, 2017.
- Rudikoff D. The relationship between HIV infection and atopic dermatitis. Curr Allergy Asthma Rep. 2002;2(4):275-281.
- Wallach D. Atopic dermatitis in adults. Fondation Dermatite Atopique. February 13, 2015. Accessed October 18, 2017.
- Hayes BB, Hille RC, Goldberg LJ. Eosinophilic folliculitis in 2 HIV-positive women. Arch Dermatol. 2004;140(4):463-465.
- Janniger CK. Eosinophilic folliculitis. Medscape. Updated April 7, 2017. Accessed October 18, 2017.
- Coffey S, ed. Molluscum contagiosum. In: Guide for HIV/AIDS Clinical Care. Newark, NJ: AIDS Education & Training Center Program National Coordinating Resource Center; 2014. Accessed October 18, 2017.
- Centers for Disease Control and Prevention. Molluscum contagiosum. Updated May 11, 2015. Accessed October 18, 2017.
- Philips RC, Motaparthi K, Krishnan B, Hsu S. HIV photodermatitis presenting with widespread vitiligo-like depigmentation. Dermatol Online J. 2012;18(1):6.
- Mutizwa M, Anadkat MJ. Dermatologic manifestations of HIV Infection/AIDS. In: Cohen J, Powderly WG, Opal SM. Infectious Diseases. 4th ed. Philadelphia, PA: Elsevier; 2017:879-887.
- Maurer TA. Dermatologic manifestations of HIV infection. Topics HIV Med. 2005;13(5):149-154.
- Prak AH. Prurigo nodularis clinical presentation. Medscape. Updated June 5, 2017. Accessed October 18, 2017.
- Morar N, Willis-Owen SA, Maurer T, Bunker CB. HIV-associated psoriasis: pathogenesis, clinical features, and management. Lancet Infect Dis. 2010;10(7):470-478.
- Mehta S, Garg A, Gupta LK, Mittal A, Khare AK, Kuldeep CM. Kaposi's sarcoma as a presenting manifestation of HIV. Indian J Sex Transm Dis. 2011;32(2):108-110.
- Rose LJ. Kaposi sarcoma clinical presentation. Medscape. Updated April 16, 2015. Accessed October 18, 2017.
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