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Chronic herpetic whitlow as the first manifestation of HIV infection

Camasmie, Helena R.; Léda, Sabrina B.C.S.; Lupi, Omar; Lima, Ricardo B.; D’Acri, Antonio M.; Martins, Carlos J.

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doi: 10.1097/QAD.0000000000001187
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Herpetic whitlow is an acute viral infection of the digits caused by the herpes simplex virus (HSV) 1 or 2 [1]. It can be easily mistaken for a bacterial felon or paronychia, having similar symptoms and signs of pain, swelling, erythema, and nonpurulent vesicle formation [2]. In many AIDS patients, cutaneous HSV infections cause extensive skin and mucosal sores, which can occasionally be the first signs of a previously asymptomatic HIV infection [3]. Their tendency to develop atypical manifestations of common infectious agents is well known, and chronic ulcerative lesions may lead to misdiagnosis. Severe manifestations of HSV suggest immunodeficiency and HIV infection should always be suspected in patients who show unusual and refractory HSV lesions [4].

A previously healthy 44-year-old man presented with painful ulcerated lesions on the distal phalanx of the second and third left fingers. His main occupation was furniture upholstery. These lesions had started 8 months prior to presentation, evolving rapidly to ulcerative, erythematous, crusted lesions, with circinate and vesicular edges, with destruction of nail structures (Fig. 1a and b). He had already been treated with systemic antibiotics without improvement. Skin biopsy showed an intraepidermal vesicle containing cells with hyperchromatic and irregular nuclei, acantholytic cells, ballooning cells, and multinucleate giant cells, supporting the diagnosis of herpetic infection. Immunohistochemistry was positive for HSV-1 and 2. Fungal culture was negative. Oral acyclovir, 400 mg five times daily, for 14 days, promoted complete healing (Fig. 1c and d). Even though the patient denied any previous skin or systemic manifestations that could raise the suspicion of immunosuppression, including previous genital or oral–labial herpetic lesions, he tested positively for HIV-1. The infection was confirmed by both enzyme-linked immunosorbent assay and western blot methods as well as p24 antigen detection. Although the CD4 lymphocyte count revealed 75 cells/mm3, the viral load count was 272.470 copies/ml. A second confirmatory blood sample was requested, but his family reported that he had passed away. No HIV antivirals had ever been initiated before his death.

Fig. 1
Fig. 1:
Clinical features and response.(a) Dorsal side of the index and long fingers, showing ulcerative, erythematous, crusted lesions, with circinate edges and nail distrophy. (b) Volar side showing erythematous circinate vesicular edges of the lesion of the long finger. (c and d) Complete healing after aciclovir 200 mg five times daily for 14 days. 501 × 375 mm (150 × 150 DPI).

Herpetic whitlow is a self-limiting disease, with lesions resolving within 14–21 days in immunocompetent individuals [5]. The lesions appear after an incubation period of 2–20 days, mainly after autoinoculation from genital lesions, associated with intense pain. Some patients report a history of a flu-like prodrome or minor local trauma; preherpetic neuralgia as well as zosteriform extension are also possible [6]. Classically, a single vesicle or cluster of clear vesicles with an erythematous base arises on the terminal phalanx of the thumb, index, or long finger near the nail. The diagnosis is mainly clinical [7,8].

However, in the presence of HIV infection, clinical polymorphism of herpetic lesions is recognized, often with atypical presentations. Immuno-synergy between both viruses has been described in many in-vitro studies, and, nowadays, it is clear that HSV infections affect HIV immunity, and vice versa [9,10]; HSV shedding occurs three to five times more frequently in immunocompromised patients [5]. Their underlying immunosuppression may lead to severe, ulcerative lesions with bacterial or fungal superinfections [10] that are more invasive and slower to heal and, if left untreated, can lead to rapid destruction of the nail [10,11]. Coinfection with HSV may also contribute to faster HIV disease progression and heightened risk of HIV transmission [12]. In advanced, HIV disease, herpetic infection is more likely to proceed to chronicity, as in our patient, who presented an unhealed lesion for 8 months. The literature even supports the possibility of gangrene development [13]. Chronic HSV infection of longer than 1-month duration in HIV patients is a criterion for the existence of AIDS condition, being included by the Centers for Disease Control and Prevention to the definition of the syndrome since 1987 [14].

Such cases require a high index of suspicion and appropriate diagnostic testing for proper management, including viral culture, serum antibody titers, PCR DNA detection, and skin biopsy [7]. PCR is more efficient than the above cited methods because it is more sensitive and specific, providing a rapid diagnosis of atypical herpetic infections, and thus preventing further complications [15].

The importance of early HSV diagnosis stems not only from its association with increased morbidity and mortality but also from the possibility of unmasking an underlying HIV infection. Delayed recognition and/or treatment exposes patients at risk of complications, which range from superinfection to herpetic encephalitis [14].

Systemic acyclovir is the therapy of choice in immunocompromised individuals with any form of herpes infection. It also helps prevent recurrent infections when daily maintenance doses are administered [4,5].

Our case reinforces previously published literature because we illustrate that herpetic whitlow can be a manifestation of immunosuppression [16], particularly when chronic and destructive, and can be the presenting manifestation of an obscure HIV/AIDS diagnosis. Atypical presentations of herpes simplex infections should prompt imediate testing for HIV.


Conflicts of interest

There are no conflicts of interest.


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