Unusual presentation of a skin rash

DISCUSSION The incidence of syphilis has been increasing in the USA since 2001. The histology of syphilis, though widely studied, still remains a diagnostic challenge, particularly when the clinical presentation does not suggest the diagnosis. We present an overview of the clinical and pathological features commonly associated with cutaneous primary and secondary syphilis, addressing, at the end, the current case. Treponema pallidum, as is well known, is the etiological organism of syphilis. Syphilis presents in one of three stages—primary, secondary and tertiary—with primary and secondary syphilis being the most common. Secondary syphilis is most commonly encountered in dermatopathology practice. The anogenital region is the most common location. However, 5% of cases arise in extragenital sites, which are termed endemic, or non-venereal, syphilis. The oral cavity is the most commonly involved extragenital site, but any site can be involved. In primary syphilis, the lesion typically appears as a chancre, a punched-out, painless ulcer that develops 20–30 days after exposure to T. pallidum and may be associated with painless lymphadenopathy. These lesions resolve within 1–5 weeks and do not scar. Secondary syphilis arises 6–8 weeks after the primary chancre. The lesions initially present as 5–10 mm erythematous macules on the head, face and neck similar to a viral xanthem. A polymorphic papular eruption subsequently occurs and consists of coppery red papules, measuring 3–10 mm in diameter. Involvement of the palms, soles and oral cavity is highly suspicious for secondary syphilis. However, this classic progression is not always observed and there is clinical significant overlap with other entities and non-specific presentations. Patients can also present with other cutaneous manifestations, some of which overlap with syphilis. These include papulosquamous/psoriasiform lesions, oral ulcers, condylomata, bullous lesions, and erythema muliforme-like folliculitis. Patients with secondary syphilis can also develop fever, headache, weight loss, myalgias and arthralgias. Left untreated, secondary syphilis resolves within 2–10 weeks. After a latent phase, patients can progress to cure with seronegativity; seropositivity without lesions; or develop lesions of tertiary syphilis. The histopathology of primary and secondary syphilis is non-specific, but there several common findings. In primary syphilis, corresponding to the punched-out appearance of a chancre, histology shows ulceration with adjacent epidermal hyperplasia and lymphohistiocytic and neutrophilic dermal infiltrates. Plasma cells can be present, and in any skin biopsy, should at least raise the suspicion for this disease. Finally, there is often prominent endothelial cell swelling of dermal blood vessels. The histology of secondary syphilis is much more variable, which accounts for the diagnostic challenge. However, the histology can coincide with the clinical presentation, which can also be normal. For example, a papulosquamous presentation will show psoriasiform changes. The inflammatory reaction patterns include granulomatous inflammation, superficial and deep perivascular and periadnexal lymphocytic inflammation, and a lichenoid-like pattern with or without basal hydropic change. Endothelial cell swelling is common, and a leukocytoclastic vasculitis has been reported, though is extremely rare. Plasma cells tend to be more numerous compared with the lesions of the primary chancre. Neutrophils may be present within the epidermis or stratum corneum, a finding that should also always raise the suspicion for syphilis in any skin biopsy. Keratinocyte necrosis has also been observed. A recent report reviewed the most common histological features in 106 cases of secondary syphilis. Although interstitial inflammation and endothelial cell swelling were the most common at 91.5% and 87.7% of cases, respectively, no single feature was present in 100% of cases. Furthermore, plasma cells were present in only 69.8% of cases. Similar to the current case presentation, the study showed that neutrophils were present but in only 32.1% of cases, which shows their poor sensitivity but higher specificity for syphilis when present. While the findings of this study may represent a sampling issue, it underscores the histological variability of syphilitic lesions. Definitive diagnosis requires identification of the spirochaete organism, which is now greatly aided by an anti-treponemal immunohistochemical stain. This is a polyclonal antibody against T. pallidum surface antigens. The organisms are typically present within the basal layer of the epidermis. The