Rare presentation of the great imitator: a rare case report

INTRODUCTION

Syphilis is a chronic disease with a waxing and waning course, the manifestations of which have been described for centuries. Malignant syphilis is a severe and rare manifestation of secondary syphilis and in recent times has been reported mostly in patients with HIV infection. Clinically, the condition is characterized by ulcerated skin lesions covered by thick crusts associated with severe constitutional symptoms. The diagnosis is often difficult and is based on clinical, histological and laboratory parameters.¹ We report an HIV-seropositive female presenting with multiple papulosquamous and ulcerative lesions diagnosed as malignant syphilis on serology and histopathology.

CASE REPORT

A 30 years old married female labourer was brought to out-patient department of Sassoon general hospital, Pune with multiple non-healing ulcers over trunk, extremities (Figure 1 and 2), face since one month (admitted from 10 April 2017 to 1 May 2017). There was history of asymptomatic genital ulcer few months back which healed spontaneously. Patient was separated from her husband and offered history of multiple unprotected penovaginal sexual exposures with a known male. There was no history of similar lesions in partner. She denied history of fever, joint pain, abdominal pain, bowel disturbances, behavioural changes, seizures. There was history of appearance of small raised reddish lesions which developed into ulcers over upper limb, face, trunk, external genitalia and trunk. Patient neglected these lesions which resulted in crusting over each ulcer. Patient was cachexic also having pallor but without lymphadenopathy. On dermatological examination there were multiple round to oval deep ulcers with raised borders over face, extremities and trunk, few of them showing keratotic heaped up brownish crusts with sero-purulent discharge. She also had few erythematus annular and gyrate scaly plaques over extremities. Ulcers over eyelids led to destruction and eversion of lower eyelid. Genitals showed single non-tender ulcer with crust over labia minora. Oral cavity showed staining of teeth and poor hygiene. Her systemic and ocular examination was unremarkable.

Patient was investigated considering differential diagnosis of secondary syphilis, Reiter’s disease, pyoderma gangrenosum and chronic cutaneous leishmaniasis. On investigations, HIV- ELISA was positive with CD4 count of 150/mm³. Her VDRL and TPHA were positive in high titres of 1:256 and 1:20480 respectively. All other routine investigations were within normal limits. Dark ground illumination from genital and cutaneous ulcers were negative. Histopathology from edge of ulcer revealed hyperkeratosis with basal cell layer vacuolisation. Deeper dermis and subcutaneous tissue showed diffuse and dense infiltration of lymphocytes and plasma cells with occasional epitheloid cell granuloma which was consistent with secondary syphilis CSF VDRL was negative (Figure 3). Thus, a final diagnosis of secondary syphilis (lues maligna variant) in a HIV seropositive host was reached. She was started on antiretroviral therapy (Tab. tenofovir, lamivudin, nevirapine), simultaneously she was given intramuscular inj. benzathine penicillin 1.2 mU in each buttock after sensitivity testing and written informed consent. Total three such injections were given at weekly interval. In view of her HIV seropositive status with low CD4 count high VDRL and TPHA titres, and non-availability of crystalline penicillin, intravenous inj. ceftriaxon (known to cross blood brain barrier)1gm twice daily was administered for ten days. Improvement in her lesions was noted within four to five days after first injection of benazathine penicillin. Ulcers healed completely with scarring and hypopigmentation (Figure 4) within 15 days. VDRL titres repeated at 8 weeks demonstrated a two-fold decline (from 1:256 to 1:128). She is under regular clinical and serological monitoring.

Commonest site for metastasis was regional lymph node. 8 patients had secondary deposits in liver, 2 were having deposit in anterior abdominal wall and two female were having secondary deposits in both ovaries.

DISCUSSION

Syphilis occurs worldwide, and the incidence varies significantly with geographic location. The total number of cases of syphilis (P&S, early latent, late, late latent, and congenital) reported to CDC increased 17.7% during 2014–2015 (from 63,453 cases to 74,702 cases). Transmission is mainly by sexual contact. The causative organism, Treponema pallidum, was first described in 1905, but because of the inability to culture the organism and the limitations of direct microscopy, serologic testing is the mainstay of laboratory diagnosis. The disease has been arbitrarily divided into several stages. The early stages (primary, secondary, and early latent) are potentially infectious. Secondary stage has varied manifestations like roseola syphilitica, popular, papulosquamous, lichenoidsyphilids, moth eaten alopecia, nickels and dimes, split papules, condyloma lata, follicular, pustular, frambosiform and corymbose eruptions.²

Luesmaligna, is one of the rare manifestions of secondary syphilis was first described by Bazinand Dubuc, who applied this term based on the bizarre clinical features and progressive course of this variant.^3,4 In contrast to tertiary syphilis, the lesions of lues maligna are multiple, have a round or oval configuration, with no tendency to central healing, and exhibit a lamellated, brown-black rupioid crust as seen in our case. Moreover, the early onset of necrotic ulcers in the disease is in contrast to the later occurring gummas of tertiary syphilis. The criteria for diagnosis of lues smaligna listed by Fisher et al include strongly positive serological test results, a severe Herxheimer reaction, and an excellent response to antibiotic therapy. In the past, serological anergia was one of the characteristic features of the disease, a concept no longer supported. Extensive clinical differential diagnosis of luesmaligna, includes pyoderma gangrenosum, vasculitis, lymphoma, leishmaniasis, leprosy, yaws, and mycobacterial or fungal infections. HIV-infected patients are at greater risk for developing malignant syphilis which may mimic various opportunistic infections and malignancies. However, no other disease process could explain the morphology of the lesions and the rapid involution with penicillin, as observed in our case.

A rise in the sero-prevalence of syphilis has been observed in various studies in India and other countries.⁵ The clinical presentation of syphilis varies in minor ways between HIV-infected and HIV-uninfected persons. HIV-infected persons are more likely to present with more than one chancre and with larger and deeper chancres in primary syphilis, and are more likely to manifest signs of secondary syphilis while a chancre is present. Because of its effect on the immune system, HIV infection is thought to increase risk of neurosyphilis. False-negative serologic test results in the setting of the prozone phenomenon and seronegative syphilis have been reported. Persistently reactive non-treponemal test results, even following appropriate treatment can occur in up to 40%. The CDC recommends CSF examination in all patients with syphilis and neurological symptoms and those with serological and/or clinical evidence of treatment failure. However, a recent study found greater success in detecting asymptomatic neurosyphilis in HIV-seropositive patients by applying serological criteria (CD 4<350/cmm and/or RPR titres >1:32) instead of stage-based criteria.⁶ The low CD4 count (150 cmm) and high VDRL titres (1:256) in our patient prompted us to perform CSF examination even in the absence of neurological symptoms or signs.

CONCLUSION

Malignant syphilis or luesmaligna, commonly reported in the pre-antibiotic era, has now seen resurgence with the advent of human immunodeficiency virus (HIV). Immunosuppression and sexual promiscuity set the stage for this deadly association of HIV and Treponema pallidum that can manifest atypically and prove to be a diagnostic challenge. The potentially fulminant course of this disease and the dramatic response to penicillin underline the importance of timely diagnosis and treatment institution.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: Not required

REFERENCES

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