CASE #1: Moth-eaten alopecia

In the United States, syphilis is most common in homosexual men, particularly those with HIV.1-4 Primary syphilis occurs three to 90 days after the initial exposure (average 21 days) and manifests as a painless ulcer, or chancre, that typically occurs on the genitals but can appear anywhere on the body. Secondary syphilis develops approximately four to 10 weeks after the primary infection. Manifestations of secondary syphilis include: condylomata lata (weeping skin lesions in the moist areas of skin and mucous membranes); silvery ulcerated patches on the mucous membranes (mouth or vagina); swollen lymph nodes; yellow eyes; red papules and plaques on the body (nickel-and-dime lesions); round hyperpigmentation of the palms and soles (copper pennies). Moth-eaten alopecia or, less commonly, diffuse scalp alopecia occurs in 4%-15% of syphilitic patients.5-9 Tertiary syphilis may occur approximately three to 15 years after the initial infection and can involve the central nervous system.

Blood tests are required to diagnose syphilis. The Venereal Disease Research Laboratory (VDRL) test or RPR are used as screening tests but can yield false positives. The T. pallidum IgG antibody test is now preferred over the RPR, given its extremely high sensitivity and specificity for syphilis. The fluorescent treponemal antibody absorption test confirms the diagnosis and also has a high degree of sensitivity and specificity but is not necessary if a T. pallidum IgG is performed. Skin biopsy can reveal many plasma cells with hematoxylin and eosin stain10 and syphilitic spirochetes with immunohistochemical staining.11

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A variety of studies have assessed the incidence of alopecia in patients with secondary syphilis. A retrospective review of 824 patients (72 heterosexual men, 695 homosexual men, and 57 women) with secondary syphilis between 1965 and 1984 at Middlesex Hospital in London found 32 of these patients had developed the alopecia of syphilis. Of these patients, five were heterosexual men, 24 were homosexual men, and three were women.12 Another study of 89 untreated patients with secondary syphilis at the University Teaching Hospital in Lusaka, Zambia, between February and December 1984, found that 10 patients had alopecia related to syphilis.1 In a study of 24 HIV positive patients with syphilis treated at the infectious dermatology outpatient clinic of the Evandro Chagas Clinical Research Institute from 1997-2003 in Rio de Janeiro, Brazil, three patients presented with patchy alopecia.13

The differential diagnosis of alopecia of syphilis includes telogen effluvium and androgenic alopecia, alopecia of thyroid disease, alopecia areata, alopecia neoplastica, tinea capitis, and trichotillomania. All cases of new-onset patchy alopecia merit testing for syphilis.

First-line treatment for uncomplicated syphilis remains a single dose of 2.4 million units of intramuscular penicillin G, according to the CDC’s 2006 guidelines.14 For those allergic to penicillin, oral doxycycline 100 mg b.i.d. for two weeks, tetracycline 500 mg four times daily for two weeks, or azithromycin 500 mg daily for one week can be given, but these are suboptimal therapies because they do not cross the blood-brain barrier, and many strains of T. pallidum are resistant. These alternate therapies are not used in pregnant women, in whom desensitization to penicillin is performed so that penicillin can be given. Ceftriaxone may be as effective as penicillin-based treatment. In patients who are HIV-positive or those whose HIV status is unknown and who are immunocompromised, three weekly doses of 2.4 million units of intramuscular penicillin G is a prudent therapeutic approach. However, serologic failure rate up to 25% has been reported.

The histology of the alopecia of syphilis can be nonspecific. Patterns include: (1) plasma cells in a perifollicular distribution; (2) an alopecia areata-like pattern in which the infiltrate is mostly lymphocytes;15 and (3) lymphocyte exocytosis into the hair matrix associated with vacuolar degeneration and scattered apoptotic cells with sparse plasma cells. Features that can distinguish the alopecia of syphilis from alopecia areata include absence of eosinophils, sparse lymphocytic infiltrate, and absence of small or abnormal anagen hair follicles. Immunohistochemical studies can show the presence of T. pallidum in the peribulbar region and penetrating into the follicle matrix.

Spirochetes are detected in 70% of secondary lesions, but whether they are directly responsible for the alopecia of syphilis remains to be determined. Quantitative evidence shows that a significant proportion of untreated secondary syphilis patients have substantial numbers of circulating spirochetes; however, how the spirochetes are able to move through the body is not well understood.16