Secondary Syphilid Developing Over Healed Lesions of Varicella: Wolf's Isotopic Response?

Isotopic response is a distinctive phenomenon in which a new skin disorder occurs at the site of another, unrelated, and already healed skin disease. Most of the cases documented in the literature were associated with herpes zoster as primary disease while the list of "second" diseases is quite long. We report here a hitherto unreported occurrence of isotopic response in which secondary syphilis occurred on the healed lesions of varicella.

What was known?

A long list of diseases, including lichen planus, morphea, granulomatous dermatitis, granuloma annulare, can occur over healed lesions of herpes virus infection as isotopic response.

Introduction

Isotopic response was first described by Wolf et al. in 1985 and hence called “Wolf's isotopic response.” Another name, “isoloci response” was also suggested. It refers to the occurrence of a new skin disorder at the site of another, unrelated, healed skin disease.[1] Diseases such as lichen planus, granuloma annulare, morphea, and scar sarcoidosis can occur over healed lesions of herpes virus infection.[1234] We present here a hitherto unreported occurrence of secondary syphilitic lesions developing over healed lesions of varicella.

Case Report

A 28-year-old housewife presented to us with a generalized, asymptomatic, reddish eruption, which had developed over the previous couple of weeks. The patient had varicella 2 months ago, which was diagnosed and treated by her family physician. The rash of varicella healed with mild dyspigmentation and superficial scarring at places. Her current lesions occurred precisely over the sites of healed lesions of varicella on the face, trunk, limbs, as well as the palms and soles. There was no history of any major illness, drug allergy, or genital ulcers. The patient denied any history of extramarital sexual exposure but her spouse had a history of sexual exposures with commercial sex workers on several occasions.

On examination, she had multiple, erythematous, mildly scaly papules and plaques almost all over her body [Figure 1]. Several small slightly depressed scars and hyperpigmented macules were visible over her face and limbs. There were sharply defined, hyperpigmented, scaly, annular lesions over the palms and soles [Figure 2]. A few mobile, nontender, rubbery lymph nodes were detected in both axillary and inguinal regions. There was no ulcer or scar on the genitalia. Few erosions were seen over her hard palate [Figure 3]. The hair and nails were normal. Systemic examination was noncontributory.

Figure 1

Widely scattered, erythematous, mildly scaly papules and plaques

Figure 2

Sharply defined, hyperpigmented, scaly, annular lesions over palms and soles

Figure 3

Erosions over hard palate

Venereal Disease Research Laboratory (VDRL) test was reactive in 1:16 dilutions. Her partner was Treponema pallidum hemagluttination assay (TPHA) positive but VDRL non-reactive. Enzyme-linked immunosorbent assay for human immunodeficiency virus (HIV-ELISA) of both was nonreactive. Routine laboratory investigations and serum chemistry panel were within normal limits.

On histopathology, there was hyperkeratosis with parakeratosis and acanthosis. There was dermal edema, profuse pandermal infiltration of chronic inflammatory cells, chiefly plasma cells and lymphocytes [Figure 4]. She was given injection benzathine penicillin (2.4 million units) intramuscularly, which resulted in rapid clinical improvement within a few days.

Figure 4

Intense upper dermal infiltrate composed primarily of plasma cells (H and E, ×100)

Discussion

The most common primary disease in an isotopic response is herpes zoster as compared with other herpes virus infections such as herpes simplex and varicella. The second unrelated diseases that may occur on the healed primary lesions include lichen planus, granulomatous dermatitis, granuloma annulare, morphea, rosacea, scar sarcoidosis, acne, Kaposi's sarcoma, erythema annulare centrifugum, xanthomas, psoriasis, and cutaneous malignancies.[1234] The exact pathogenesis of isotopic response is unknown. Some authors have suggested immunologic and vascular changes following neural alteration by herpes virus, as causative factors for the localization.[15] It is further supported by isolation of herpes virus in some studies.[6] The role of neuropeptides, including vasoactive intestinal peptide, neuropeptide Y, calcitonin-gene-related peptide, and substance P, was also implicated to influence the immune system.[7] Thus, a disturbed nervous system due to herpes virus infection may alter the immunologic system and then consequently the skin that leads to the localization of the second disease.

The secondary stage of syphilis, “the great imitator,” can present with a myriad of clinical and histological features. Lesions called syphilids may develop in 80-95% of the cases, usually 3-12 weeks after the appearance of a chancre, which may be unnoticed, especially in women. It is characterized by a maculopapular rash, symmetrically distributed, involving the palms and soles, associated with flu-like prodrome and lymphadenopathy. Papular syphilids are observed in approximately 12% of the cases and may be of different patterns, such as papulosquamous, follicular, lenticular, corymbose, lichenoid, nodular, or annular.[8]

Serological tests such as VDRL, RPR, TPHA, and histologic features of psoriasiform or lichenoid epidermal hyperplasia, a dermal, predominantly plasma cell infiltrate corroborate the diagnosis of secondary syphilis.[9]

We considered guttate psoriasis, lepromatous leprosy, sarcoidosis, and pityriasis lichenoides et varioliformis acuta in the differential diagnosis. The presence of risk factors, absence of anesthesia or pruritus, positive serology, corroborative histopathology, and dramatic response to penicillin helped us to establish the diagnosis of secondary syphilis.

In the literature, several cases of isotopic response and many atypical varieties of secondary syphilis have been documented. However, to the best of our knowledge, secondary syphilis occurring as “second disease” over healed lesions of varicella as Wolf's isotopic response has not been reported earlier.

What is new?

Secondary syphilid can be considered as the newest among those diseases that can develop over healed lesions of herpes virus infection as isotopic response.