Syphilis is a Rare Cause of Erythema Nodosum: A Case Report

Introduction

Erythema nodosum (EN) is a painful inflammation of subcutaneous fat tissue. It is the most common type of panniculitis.¹ The first cause of EN is idiopathic, but classically the main causative agents are infectious pathogens such as Streptococcus, Yersinia spp, Mycoplasma, Chlamydia, Histoplasma, Coccidioides, and Mycobacterium; inflammatory diseases such as sarcoidosis and enteropathies; pregnancy; oral contraceptive pills; and paraneoplastic syndrome. However, we reported the case of a 42-year-old female living in Reunion Island, with no medical history and receiving no medical treatment, presenting an EN where the etiology was found to be a rare diagnosis: syphilis.

Observation

Following three weeks of symptoms, a 42-year-old female presented a persistent and generalised rash, characterised by a pruritic maculopapular rash on the lower limbs (Figure 1A), later extending over the trunk and upper extremities but sparing the palms. She had no fever and no palpable lymph nodes. She also presented a painful inflammatory and well-defined hypodermic lesion on the right forearm (Figure 1B) that had developed for 48 hours previously, which was clinically suggestive of an EN. Two skin biopsies were performed on papular lesions (left leg) and on the EN. Awaiting biological and pathological results and suspecting a cutaneous sarcoidosis, dermocorticoids were proposed for the legs. Pathology reported a granulomatous dermatitis with a lichenoid infiltrate in the leg (Figure 1C) and confirmed the EN with a septal panniculitis on the arm (Figure 1D). These results supported physicians’ sarcoidosis hypothesis, but no improvement was achieved after dermocorticoids treatment. Before starting a systemic treatment, a blood test diagnosed syphilis (TPHA > 1/1280, VDRL 1/32; Biorad^®). Targeted re-interviewing reported a recent divorce and new partners in the last 6 months with unprotected sex. The entire complementary exam presented an elevated CRP (110 mg/L), a polyclonal hypergammaglobulinemia (but no dysimmunity), no other infection (Yersinia, Chlamydia, Mycoplasma, HIV, HBV, HCV, tuberculosis), no other biological dysfunction, normal ECG and no evidence of pulmonary sarcoidosis on a chest CT scan. Given these results, an immunohistochemistry to Treponema pallidum on skin biopsies was requested but came back negative (long-distance transport from Reunion Island to Germany might explain this result for the leg). However, the pathologist reported plasma cells in the leg biopsy, which were highly suggestive of syphilis. The CT scan did not show any signs of visceral syphilis. The patient was treated with an intramuscular injection of benzathine-penicillin G (BPG): 2.4 million units, and complete healing of symptoms occurred within 15 days, confirming the diagnosis of syphilis with EN.²

Figure 1 Clinical and pathology examination of skin lesions presented by the patient. (A) Maculopapular rash on the lower limbs with Biett collarette; (B) erythema nodosum on the right forearm; (C) granulomatous dermatitis with a lichenoid infiltrate; (D) septal panniculitis.

Discussion

Syphilis is a sexually transmitted infection characterized by an evolution in three stages if untreated.² Dermatological manifestations occur, particularly in the secondary phase of the disease. However, EN is not described as a classical symptom of this disease, and few cases of EN related to syphilis have been reported (Table 1).^3–6 If a patient infected with syphilis is undiagnosed and therefore untreated, progression to the tertiary phase with visceral manifestations may occur. Here, despite the negative Treponema immunohistochemistry in the biopsy of the leg, this diagnosis appeared to be a result of syphilis in view of (i) exclusion of frequent causative agents, (ii) presence of plasma cells in the leg biopsy and (iii) regression after BPG.

Table 1 Case Reports of Erythema Nodosum Associated with Syphilis

In a context of resurgence of this infection, mainly among men who have sex with men in developed countries, and also among heterosexuals and women in different parts of the world, it seems primordial to keep in mind this rare differential diagnosis in the presence of an EN.^7–10