Syphilis: a forgotten disease?
M Konstantopoulou1, U Andrady2, M G Lord3, A W Macfarlane1
Dermatology Online Journal 12 (7): 27

1. Department of Dermatology1, 2, and 3, Ysbyty Gwynedd Hospital, Bangor, UK. Department of Genitourinary Medicine, Ysbyty Gwynedd Hospital 3. Department of Pathology, Ysbyty Gwynedd Hospital


We report a case of secondary syphilis in a 54-year-old, bisexual, HIV positive man. Although syphilis is a well-known sexually-transmitted infection, it is not widely seen nowadays. However, a possible diagnosis of syphilis should not be overlooked in any individual, irrespective of HIV status.

Establishing a diagnosis of syphilis can be extremely difficult because syphilis is a great mimic in clinical morphology and histology. Concurrent infection with HIV may complicate the clinical presentation, diagnosis, and management. Serology and biopsy samples with Warthin Starry staining or darkfield microscopy can be extremely helpful.

Clinical synopsis

Figure 1 Figure 2
Figure 1. Generalized purpuric, papulonodular eruption (also present on lower half of body and face)
Figure 2. Palms showing erythematous macules typical of secondary syphilis

A 54-year-old bisexual man, recently diagnosed HIV positive, presented with a 2-month history of a non-itchy generalized skin eruption, tiredness, fever, and night sweats. There was no history of prior skin disease and he was not on medication. He had a generalized macular, papulonodular, purpuric eruption (Figs. 1 and 2), patchy alopecia, generalized lymphadenopathy, and oral candidiasis. His CD4 count was 300 cells/mm3, HIV RNA viral load 71,000 copies/ml. Chest X-ray, CBC, blood cultures, seroimmunology for lupus erythematosus, ANCA, and serum biochemistry including liver transaminases were normal or negative. His EBV and CMV IgG were positive. The toxoplasma IgG was negative.

Figure 3a Figure 3b
Figure 3a. Upper dermal infiltrate centered on blood vessels, showing marked preponderance of plasma cells
Figure 3b. Warthin-Starry stain showing spiral organism typical of T pallidum

A skin biopsy was obtained from the right side of his trunk and showed a plasma-cell vasculitis with a pronounced inflammatory infiltrate in the upper dermis extending around vessels into the lower dermis (Fig 3a). There was an overwhelming preponderance of plasma cells, some of which were bi- or multi-nucleate. Warthin-Starry stain showed occasional structures consistent with Treponema pallidum (Fig 3b). Syphilis serology was positive (ELISA IgM and IgG positive, VDRL 1:512, and TPPA 1:40,960). He was treated with procaine penicillin and probenecid daily for 17 days.


Syphilis (the great imitator) is a spirochetal disease with protean manifestations, especially in HIV infected individuals. Broadly, there are two stages: early and late. Early syphilis is infectious and includes primary, secondary, and early latent syphilis (within the first 2 years of infection). Late syphilis comprises late latent, benign late, cardiovascular syphilis, and neurosyphilis. Patients who are HIV positive are more likely to have secondary syphilis than any other stage and can present with a wide spectrum of manifestations [1]. Recently, there has been a dramatic rise in cases of early syphilis in the UK irrespective of HIV status [2].

Recognized features of secondary syphilis include maculopapular and pustular skin eruptions and pigmentary changes, nail and hair abnormalities, mucous membrane involvement (with or without lymphadenopathy), gastric, renal, ophthalmological, and neurological manifestations, sensorineural hearing loss, and hematological and bone changes. Symptoms and signs may be mild and clinically overlooked or severe enough to need inpatient care. Although syphilis in HIV infection usually presents with the common features of secondary stage disease, it may be abnormally severe or exhibit manifestations such as accelerated progression to tertiary syphilis, a greater likelihood of neurosyphilis, or cardiovascular syphilis [3]. Lues maligna or ulceronodular syphilis is a rare manifestation of secondary syphilis but one seen in HIV positive patients [4].

Serology testing for syphilis in HIV positive patients appears to be as reliable as in HIV-negative patients, but the incidence of biological false-positive reagin tests (RPR or VDRL) is higher than normal because of polyclonal B-cell activation [3]. Clinically more relevant in HIV positive patients is a false negative serological response resulting from very high anti-treponemal antibody titers that interfere with the reagin tests. This prozone phenomenon is also seen in secondary syphilis without HIV [5], so if the RPR or VDRL is negative but syphilis is still suspected clinically, repeat testing with a dilution of titers should be requested. In some instances syphilis is diagnosed by means other than serology, such as biopsy samples with Warthin-Starry staining or darkfield microscopy.

Penicillin remains the treatment of choice, although alternatives such as oral doxycycline are also recommended in published guidelines [6]. Patients who are HIV positive and pregnant women should receive penicillin, and desensitization is recommended for penicillin-allergic patients [6].


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