From the Department of Internal Medicine, Nassau County Medical. Center, East Meadow, and the State University of New York at Stony. Brook, Stony Brook, NY ...
DISSEMINATED CUTANEOUS HERPES SIMPLEX VIRUS TYPE-i WITH INTERSTITIAL PNEUMONIA AS A FIRST PRESENTATION OF AIDS Sanusi H. Umar, MD, and Anil Kanth, MD East Meadow and Stony Brook, NY
Recognition of cutaneous herpes simplex virus (HSV) in acquired immunodeficiency syndrome (AIDS) can be difficult because of its atypical presentations. Pneumonia in AIDS is complex with many possible etiologies. Identification of HSV preceded by atypical cutaneous manifestation and pneumonia is critical, given the poor prognosis when treatment is delayed or not prescribed. We report a 62-year-old patient with undiagnosed HIV infection who presented with disseminated cutaneous lesions resembling impetigo as his first presentation of AIDS. Subsequent confirmation that HSV was responsible led to appropriate treatment of this and the complicating HSV pneumonia. This report emphasizes the importance of the early recognition of atypical cutaneous HSV in patients with AIDS. (J Nad Med Assoc. 1999;91 :471-474.)
Key words: disseminated cutaneous HSV-1 * interstitial pneumonia * AIDS
Although the Centers for Disease Control and Prevention (CDC) criteria for acquired immunodeficiency syndrome (AIDS) includes herpes simplex virus (HSV) causing chronic mucocutaneous ulcerations persisting for more than one month, gastrointestinal, or pulmonary or disseminated infection, there is a paucity of case reports documenting disseminated cutaneous HSV' or HSV pneumonia.23 The observation of localized cutaneous HSV and HSV pneumonia in the same individual was noted in a single autopsy report but was not established antemortem since bronchoalveolar lavage (BAL) speciFrom the Department of Internal Medicine, Nassau County Medical Center, East Meadow, and the State University of New York at Stony Brook, Stony Brook, NY. Requests for reprints should be addressed to Dr Sanusi H. Umar, Charles Drew Medical Ctr, Division of Dermatology, 12021 S Wilmington Ave, Los Angeles, CA 90059. JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 91, NO. 8
men was negative for HSV. This report describes a patient with disseminated cutaneous HSV who then developed interstitial HSV pneumonia as the first manifestation of AIDS.
CASE 'REPORT A 62-year-old heterosexual white man was admitted to the Nassau County Medical Center in Long Island, NY with a one-week history of generalized pruritic rash and chills, and a weight loss of 4.5 kg in the preceding two months. The rash had progressed despite a one-week course of amoxicillin and topical cotrimazole. The past medical history was unremarkable, and other than unprotected sex with multiple partners, there were no risk factors for -human immunodeficiency virus (HIV) infection. On admission, temperature was 38.10C. The rash was generalized and consisted of small ulcerative lesions with purulent discharge. The scalp was covered extensively with a sebborheic dermatitis. There were multiple excoriations in the perianal region. 471
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The remainder of the physical examination was unremarkable. A chest radiograph was normal. Hemoglobin was 13 g/dL, hematocrit 39%, white blood count 8200/mm3, with a normal differential other than an eosoniphilia of 12%, platelets 163,000/mm3, blood urea nitrogen 36 mg/dL, and creatinine of 1.1 mg/dL. Hepatic enzymes were normal. A presumptive diagnosis of impetigo and perianal candidiasis was made and amoxicillin was continued, and mupirocin and lotrimin were added. Over the next 11 days, the patient's fever intensified (Figure 1), the lesions became more dense and pronounced, and the failure to respond to therapy raised the possibility of another diagnosis. Swabs from skin lesions on the chest were negative for bacteria, acid fast bacilli, and fungi. Direct immunoflourescent monoclonal antibody staining for HSV and varicella zoster also were negative. However, a viral culture was positive for HSV-1. Acyclovir 250 mg was started intravenously every eight hours, and all other antibiotics and antifungal agents were discontinued. On day 14, respiratory distress and bilateral interstitial infiltrates were first manifested. Arterial blood gas revealed a pH of 7.48, partial pressure of carbon dioxide 54, and partial pressure of oxygen of 43, with an alveolar-arterial gradient of 58. CD4 and CD8 cell counts were 50/mm3 and 620/mm3, 472
respectively. Acyclovir was increased to 500 mg every eight hours. The patient was anergic to purified protein derivative and an anergy panel. The patient refused an HIV test. By day 16, the patient had become afebrile, and by day 19, skin lesions had completely resolved (Figure 2). Respiratory status improved markedly with complete radiographic resolution of lung infiltrates and a normal blood gas at room air. The patient was discharged on day 22 on acyclovir. Pneumocystis carinji pneumonia (PCP) and Mycobacterium avium prophylaxes were prescribed because of the abnormally low CD4 cell count. On a subsequent admission one month later for acyclovir renal toxicity, an HIV test was positive by ELISA and Western blot. An HSV esophagitis resulted in a third admission four months proceeding the initial presentation.
DISCUSSION Herpes simplex virus co-infection in HIV disease has attracted attention as a frequent complication of impaired immunity and conversely as a risk factor for HIV transmission. Further, HSV reactivation has been shown to influence HIV replication.5 Cutaneous HSV in early HIV disease is typical, affecting mucocutaneous areas, whereas in advanced HIV when immunity is compromised, the presentation is more often atypical, chronic, more disseminated, recurrent, and acyclovir-resistant. These atypical features often are not recognized and may explain why even though the current CDC definition of AIDS includes disseminated cutaneous HSV only few cases have been reported. This difficulty in diagnosing cutaneous HSV in AIDS is further complicated by the low yield of accepted laboratory diagnostic procedures. Langtry et all was the first to focus on the atypical presentations of HSV in patients with AIDS. In their three cases, cutaneous lesions were not specific and only one had a disseminated picture, while another had lesions that were initially mistaken for tuberculous ulcerations. They reported a response to acyclovir despite negative cultures for HSV. Other atypical cutaneous HSV lesions in AIDS includes indolent penile ulcers,6 herpetic whitlows,7 and neurotic excuriations.8
Although the CDC criteria for AIDS with regard to cutaneous HSV requires the existence of chronic HSV mucocutaneous ulcerations persisting for more than one month, studies suggest that cutaneous JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 91, NO. 8
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Figure 2. (A) Healed cutaneous ulcerations on the chest. (B) Peri-anal excoriations. HSV considered atypical where the lesions are unusual in appearance and location or disseminated usually signifies a profound reduction in cellular immunity.9 Hence, the finding of any atypical cutaneous HSV presentation should prompt a search for HIV disease. The differential diagnosis of a cutaneous lesion resembling HSV in an AIDS patient is diverse and includes cutaneous tuberculosis,l neurotic excoriations,8 whitlow (staphylococal infections),7impetigo when secondary impetiginization occurs, and herpes zoster.10 Scalp sebborheic dermatitis-like features found in this patient are not unusual because it is the most common dermatologic finding in HIV disease among the spectrum of papulosquamous conditions"l that also includes psoriasis-like and pityriasis rosea-like eruptions. In a study by Froschl et al'2 in Germany, a sebborheic dermatitis-like rash was found in 31% of nonimmunocompromised HIV patients and in 83% of patients with AIDS. Histopathologically, these three types of lesions differ from the classic presentation of psoriasiform dermatoses (PD) in that plasma cells, necrotic keratinocytes, and leukocytoclasis are predominant features'3 and have led to the term-like eruptions or AIDS-PD. In these eruptions, biopsy reveals an epidermal expression of HSP65 that is irregular and less intense, less tendency to perinuclear JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 91, NO. 8
arrangement when compared with the classic PD.'4 These findings have led to the hypothesis that AIDSPD results from an interplay of T cells and keratinocytes in an immunocompromised host.'40f further interest is the frequent association of AIDS-PD with mycotic infections; hence, a prudent management approach should include skin scrapings to rule out this possibility.'5 Herpes simplex virus pneumonia is treatable, but, if not managed early, often results in acute respiratory distress syndrome, with the need for mechanical ventilation resulting in a mortality rate >80%./16 Interstitial pneumonia, occurring in the setting of cutaneous HSV infection as in this patient, mandates that HSV pneumonitis be strongly considered and that prompt and effective treatment be instituted even in the absence of diagnostic BAL findings. The incidence of HSV pneumonia in AIDS patients regardless of the presence or absence of cutaneous HSV has been underestimated, with many cases being managed as PCP infection. Bozzette et a12 examined BAL specimens from 327 patients suspected of having PCP and found HSV in 16 (5%). This suggests that analyses of all BAL specimens in AIDS patients suspected of having PCP should include appropriate studies for HSV. Disseminated HSV responds well to acyclovir when treatment is initiated promptly. In view of the 473
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high incidence of renal toxicity of acyclovir, when used in combination with other potential renal toxic agents frequently used in HIV management as was the case in the present case, frequent assessment of renal function both in-hospital and after discharge is essential and critical. Other frustrations faced by clinicians managing HSV disease in AIDS includes the emergence of both acyclovir-resistant and foscarnet-resistant HSV strains." The chronicity and recurrence of HSV infections in the AIDS patient often necessitates prophylactic or suppressive treatment.18
CONCLUSION Disseminated cutaneous HSV can be the first presentation of AIDS. Atypical cutaneous HSV lesions should be considered in all AIDS patients with unusual or difficult-to-diagnose skin lesions. Empiric treatment with acyclovir is essential when clinical suspicion is high or pathologic findings are nondiagnostic because of the high risk-to-benefit ratio when treatment is delayed or prescribed not at all. When interstitial pneumonia is present in the AIDS patient with atypical HSV skin lesions, early treatment becomes even more imperative.
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