Chronic mucocutaneous herpes (CMH) is the infection caused by the herpes simplex viruses (HSV) type 1 and 2, lasting more than four weeks, resistant to classic anti-herpetic treatment.1

CMH has atypical clinical manifestations, requiring confirmation by a complementary cytological, laboratory, or anatomopathological method.1 In general, it is clinically characterized by painful, ulcerated lesions that show progressive growth, occasionally to verrucous, vegetative, or tumor forms, particularly in HIV immune reconstitution syndrome.1,2 The treatment is challenging: the host usually has marked immunosuppression, which hinders the effective defense response against the offending agent and efficient wound healing and, on the other hand, intrinsic viral resistance to classic drugs such as acyclovir and valacyclovir has been increasingly described.3–6

Ten patients with clinical and laboratory diagnoses of CMH were included in a retrospective study in the Dermatology Clinic of a tertiary hospital in São Paulo, Brazil, between January 2013 and November 2020. Detailed data are shown in Table 1 and clinical aspects in Figs. 1 and 2. It is emphasized that all patients reported a history of local herpetic disease, indicating that the CMH forms would be variants of recurrent herpes and not of primary infection.

Figure 1.

Chronic mucocutaneous herpes: clinical images of three male patients included in the study (A, Case 7; B, Case 6; C, Case 9).

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Figure 2.

Chronic mucocutaneous herpes: clinical images of three female patients with genital and gluteal lesions (A, Case 3; B, Case 2; C, Case 4).

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Anogenital cases of HSV-2 have up to six times more episodes of recurrence than those attributed to HSV-1, in addition to manifesting in a subclinical form in 10%‒25% of patients.7 Tzanck test (Fig. 3) and immunohistochemistry for HSV1 + 2 do not differentiate between parasitism resulting from HSV1 or HSV2. The diagnosis of CMH cases should be performed preferably with a skin biopsy, as the sample can also be analyzed by in situ hybridization and polymerase chain polymerase chain reaction (PCR aiming at viral identification.3,4,8 Moreover, the test rules out differential diagnoses of genital ulcers such as syphilis, cytomegalovirus infection, chancroid, fungal or protozoal infections.

Figure 3.

: Smear of lesions submitted to rapid panoptic staining, showing multinucleated epithelial cells, called Tzanck cells, suggesting viral inclusion by herpes virus (×400).

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The treatment in 70% of the cases was carried out with acyclovir, followed by valacyclovir in 20% and foscarnet in 10%. Two female patients had the verrucous hypertrophic form, and the therapeutic approach in these cases was as described by several authors, with an antiviral combined with local therapy (surgical excision or topical imiquimod), with significant improvement (Fig. 4).2,3

Figure 4.

Patient with hypertrophic chronic mucocutaneous herpes tumor. A, Pre-treatment. B, In the immediate postoperative period after surgical removal of the tumor lesion. C, After 4 weeks of surgical excision, with the surgical wound undergoing healing. D, After 10 weeks of the procedure, with the healed lesion.

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The recommended treatment for chronic ulcerated forms is the use of oral acyclovir, at a daily dose of 1,000 mg, initially for one to two weeks. This daily dose can be maintained or increased to 4,000 mg, and the medication can be administered intravenously (10 mg/kg 3×/day) in cases of resistance or to overcome bioavailability problems for the same period. If therapeutic failure persists, oral valacyclovir (daily dose of 3,000 mg) or famciclovir (daily dose of 550‒1,500 mg) is indicated for one to two weeks. If it is considered a resistant viral population, whose main associated factor is the prolonged use of antivirals, the use of antivirals with other mechanisms of action, such as foscarnet, cidofovir, and vidarabine, is suggested.1,3,4,8 In addition to this targeted drug approach, aimed at a direct fight against HSV, it is essential to reverse the patient immunosuppression.

Chronic mucocutaneous herpes, despite being well established in the literature, is rare and little known. The diversity of clinical presentations and therapeutic resistance reinforces the challenge in the management of this disease. Thus, knowing the aspects detailed in the present report helps physicians in the diagnosis and management of the disease, optimizing therapy, and reducing patient morbidity.