First report of tertiary syphilis presenting as lipoatrophic panniculitis in an immunocompetent patient

Introduction

Although benzathine penicillin G (BPG) is considered the gold standard for treatment of syphilis, luetic late complications are still reported. ¹ Tertiary granulomatous lesions may develop after variable time from the initial infection, potentially involving every organ. We describe herein a woman who developed subcutaneous gummas although she had been treated for syphilis two decades earlier.

Case report

A 65-year-old woman presented with a 12-month history of subcutaneous nodules in the trochanteric regions. One of the lesions has been surgically removed eight months earlier, but it had relapsed. The pathologist had diagnosed desmoplastic fibroblastoma. The patient acknowledged to have been treated for late latent syphilis 25 years before with BPG 2.4 million units/weekly for three weeks intramuscularly. Subsequently, she had suffered from pulmonary and bone tuberculosis and chronic obstructive pulmonary disease. Physical examination revealed an indolent subcutaneous nodulo-cystic lesion of hard consistency, movable and covered by normal skin in the right trochanteric region (Figure 1(a)) and similar smaller lesions in the left trochanteric and right paraspinal regions. Routine laboratory investigations (blood count, liver and kidney function, blood glucose) were normal. Antinuclear antibodies, angiotensin-converting enzyme, antibodies against human immunodeficiency virus and hepatitis B and C viruses were negative. Quantiferon test indicated a probable latent M. tuberculosis infection. Evidence of T. pallidum latent late infection was the presence of IgG antibodies (enzyme immunoassay) against T. pallidum (IgM negative), and the positive non-treponemal (venereal disease research laboratory, VDRL) and treponemal (T. pallidum hemagglutination assay, TPHA) tests with titres of 1/640 and 1/1280, respectively. A new histological examination of two nodules revealed interstitial edema and lymphoplasmocytic-histiocytic inflammatory infiltrates with steatonecrosis (Figure 1(b)). The search for acid-resistant alcohol bacilli (Ziehl Neelsen method) was negative whereas immunohistochemical staining for T. pallidum detected a limited number of spirochetes close to the atrophic adipocytes (Figure 1(c)). Diagnosis of lypo-atrophic panniculitis tertiary syphilis was made. We propose to the patient to take a cerebrospinal fluid (CSF) test to exclude syphilis infection of the central nervous system, but she refused to undergo the procedure. The patient was treated with BPG 2.4 million units/weekly for three weeks, intramuscularly. In addition, she has been treated with ceftriaxone 1 g/daily intramuscularly for 10 days and oral doxycycline 100 mg twice daily for 20 days, according to our reported enhanced therapeutic regimen for syphilis. ¹ Complete clinical resolution was achieved in four weeks and an eightfold reduction of VDRL and TPHA titres in six months. OPEN IN VIEWER

Discussion

Today, tertiary syphilis is rare, primarily for the standard penicillin therapy for early syphilis and because of the widespread antibiotics use for concomitant infections. The disease, potentially involving every organ (including the cardiovascular and nervous system), is characterized by a hyperergic inflammatory-immunological reactions against few spirochetes which have survived in different tissues. The characteristic lesion is the gumma, a granulomatous, nodular lesion with a central stringy core resulting from a coagulation necrosis process, which usually develops several decades after the onset of T. pallidum infection. Gummas histopathology reveals tubeculid-like granulomas with epithelioid cells, plasma cells, lymphocytes, multinuclear giant cells and central necrosis. ² Low numbers of treponemas may be found with very sensitive methods, such as immunohistochemistry. ³ Clinically, the gummatous lesions are small, subcutaneous nodules that involve the dermis, localized on the scalp, forehead, oral/nasal cavity, lips or genitoanal region. The lesions may be livid or red-brown in colour, and after several weeks, may become ulcerated. Severe courses are possible, especially when the cardiovascular or nervous systems are involved. Syphilis very rarely manifests as panniculitis. To our knowledge, only two cases of panniculitis syphilis have been described, both associated to secondary syphilis and referred to ‘newly diagnosed with syphilis’.^4,5 Conversely, in our case syphilis has already been diagnosed and treated. The possibility of a T. pallidum reinfection after the treatment was improbable because of the poor general state of our patient, as showed by her medical history, and because she denied risky sexual intercourses. Above all, a significant increase of VDRL/TPHA and the presence of IgM antibodies by enzyme immunoassays, that might have demonstrated a newly acquired infection, were never observed over the years of follow-up. One wonders whether BPG is really effective in eradicating the infection. Millions of patients are treated with intramuscular BPG according to official recommendations, but neurosyphilis still takes a heavy toll on them. Despite conventional treatment, 20% of patients without HIV and almost 60% of patients with HIV and early-stage syphilis already have neurosyphilis, ⁶ and almost 13% of syphilis patients have T. pallidum in CSF, ⁶ suggesting that treponemes invade the central nervous system early and cannot be eradicated with BPG. Penicillin may fail to achieve sufficient concentrations in CSF, treponemes may develop mechanisms of phenotypic tolerance to penicillin or treponemes may escape immune surveillance. Regardless of the mechanism, BPG may be inadequate to prevent late-stage complications. ⁷

Indeed, our confidence in the BPG conventional regimen as the gold standard for syphilis treatment has recently wavered as the result of studies conducted in both immunocompetent and HIV-infected patients. ³ Therefore, we have adopted an enhanced therapy that employs doxicyclin and ceftriaxone in addition to penicillin, ¹ obtaining a very rapid resolution both clinically and serologically. This regimen, differently from the standard one, should reach more easily treponemicidal levels in the CSF and other ‘hard districts’ better preventing late complications.

In conclusion, we describe the first case of tertiary syphilis presenting as panniculitis in an immunocompetent patient, demonstrating that subcutaneous fat may be another organ infected in tertiary syphilis. Since syphilis remains ‘the great simulator’ and can simulate every other disease, we should maintain a high level of suspicion in order to achieve a correct diagnosis of syphilis at any stage.