Ulceronecrotic rash in an immunocompetent individual.

A 28-year-old woman presented with a 6-week history of a pustular rash that began on her ankles and spread upward. Two weeks prior to presentation, she began experiencing eye redness, swelling, and vision loss with enlarged lymph nodes and fatigue. Examination revealed ulcerated papules and plaques involving the face, shins, knees, and thighs (Fig 1). The palms and soles were spared. Postauricular and cervical lymphadenopathy was present, and there was bilateral periorbital edema with conjunctival injection (Fig 2). Punch biopsy demonstrated a lichenoid granulomatous dermatitis with plasma cells (Fig 3).

Fig 1

Fig 2

Fig 3

Question 1: What is the most likely diagnosis?

Pityriasis lichenoides

Malignant syphilis

Primary cutaneous aggressive epidermotropic cytotoxic T cell lymphoma

Ecthyma

Necrolytic migratory erythema (NME)

Answer:

Pityriasis lichenoides – Incorrect. Pityriasis lichenoides presents as papules that acutely develop hemorrhagic or necrotic crusts. Histopathology demonstrates a lichenoid interface dermatitis with a superficial and deep lymphocytic infiltrate; plasma cells and granulomas are not present.

Malignant syphilis – Correct. Malignant syphilis is a rare, ulceronecrotic subtype of secondary syphilis that begins with a prodrome of fever, fatigue, and lymphadenopathy. This is followed by a diffuse eruption of erythematous papulopustules that eventually ulcerate. Diagnostic criteria are summarized in Table I. The patient presented had a positive Treponema pallidum IgG serology followed by a serum rapid plasma reagin of 1:128. Enzyme-linked immunosorbent assay for Human immunodeficiency virus (HIV) and an interferon-gamma release assay were negative. Although this patient also had ocular findings, ocular syphilis is not required for a diagnosis of malignant syphilis. Histopathologic findings demonstrate an interface tissue reaction, epidermal hyperplasia, and psoriasiform features. The most frequently described pattern reflects a lymphoplasmacytic dermal infiltrate; a granulomatous infiltrate can also be observed. Immunohistochemistry for T pallidum is up to 80 percent sensitive in secondary syphilis.

Table I

Diagnostic criteria for malignant syphilis∗

Characteristic clinical and histopathologic morphology: crusted or scaly papules and pustules that evolve into ulceronecrotic lesions, with a characteristic interface tissue reaction, epidermal necrosis, and spongiosis.

High titer† treponemal serological tests

Jarisch-Herxheimer reaction: a transient clinical phenomenon with fever, chills, headache, nausea, vomiting, tachycardia, and hypotension due to the breakdown of spirochetes and release of toxins and cytokines during antibiotic treatment.

Resolution of lesions following therapy with benzathine penicillin G

The majority of reported cases fulfill at least 3 criteria.

Serologic titers >1:32 based on previously reported cases.

Primary cutaneous aggressive epidermotropic cytotoxic T cell lymphoma – Incorrect. This rare lymphoma presents as papules and plaques with central necrosis and ulceration. Histopathology includes prominent epidermotropism by atypical lymphocytes, rather than an interface dermatitis with mixed inflammation including plasma cells. Immunohistochemistry is required for distinction from other cytotoxic lymphomas, specifically gamma-delta (γδ) T cell lymphoma and natural killer/T cell lymphoma.

Ecthyma – Incorrect. Ecthyma is a deep pyoderma that is often caused by group A beta-hemolytic streptococci, beginning as a small vesicle or pustule that ulcerates. Histopathology demonstrates ulcer and abscess.

NME – Incorrect. NME is characterized by erythematous plaques that develop crusted erosions. These erosive plaques often resolve and reappear elsewhere. Histopathology demonstrates a psoriasiform dermatitis with keratinocyte pallor, dyskeratosis, and ballooning degeneration.

Question 2: What condition is most often associated with this diagnosis?

Epstein–Barr virus (EBV)

Glucagonoma

Inflammatory bowel disease (IBD)

HIV

Systemic lupus erythematosus (SLE)

Answer:

EBV – Incorrect. The EBV causes infectious mononucleosis, which manifests as splenomegaly, pharyngitis, and bilateral cervical lymphadenopathy. A morbilliform rash can occur following the administration of an aminopenicillin.

Glucagonoma – Incorrect. Glucagon-secreting tumors are associated with NME, which is described above.

IBD – Incorrect. IBD can be associated with erythema nodosum (EN) and pyoderma gangrenosum (PG), neither of which is seen here. EN does not ulcerate, and the presentation of PG is notable for ulcers with characteristic undermined edges and surrounding violaceous borders. EN is characterized by a septal granulomatous panniculitis, while established lesions of PG demonstrate ulceration and diffuse neutrophilic infiltrates.

HIV – Correct. Malignant syphilis is often associated with HIV infection or immunosuppression. In a systematic review of 45 patients from 2014 to 2018, 75% were HIV-positive. Decreased cell-mediated immunity, defective macrophage function, and a blunted humoral response in immunosuppressed patients enable greater virulence in T pallidum and subsequent severe clinical manifestations. The case presented here is notable in that the patient was healthy, without comorbidities or immunosuppression. All patients diagnosed with syphilis, including malignant syphilis, should be screened for HIV. Additionally, it is recommended that HIV-negative patients with neurosyphilis, ocular syphilis, and otosyphilis are offered HIV pre-exposure prophylaxis, as syphilis is a significant risk factor for HIV infection.

SLE – Incorrect. Necrotic findings associated with SLE include antiphospholipid syndrome, which presents with retiform purpura and a thrombotic vasculopathy, and Rowell syndrome or cutaneous lupus with epidermal necrosis.

Question 3: What is the treatment of choice for this condition?

Cyclophosphamide, doxorubicin, vincristine, and prednisolone for 21 days

Valacyclovir 500 mg twice daily for 3 days

Benzathine penicillin G 2.4 million units intramuscular weekly for 3 weeks

Doxycycline 100 mg twice daily for 4 weeks

Prednisone 30 mg daily for 7 days

Answer:

Cyclophosphamide, doxorubicin, vincristine, and prednisolone for 21 days – Incorrect. This regimen, commonly referred to as CHOP therapy, is the most commonly used therapy for primary cutaneous aggressive epidermotropic cytotoxic T cell lymphoma.

Valacyclovir 500 mg twice daily for 3 days – Incorrect. This is the treatment for recurrent herpes simplex virus infection.

Benzathine penicillin G 2.4 million units intramuscular weekly for 3 weeks – Correct. Most cases of malignant syphilis have responded more significantly to this treatment rather than a single dose of penicillin, which is usually the treatment of choice for secondary syphilis. Due to this patient’s syphilitic uveitis, she was treated with intravenous penicillin G for 14 days, as well as sub-Tenon triamcinolone, to reflect treatment guidelines for ocular syphilis.

Doxycycline 100 mg twice daily for 4 weeks – Incorrect. While this treatment has been proven to be effective in penicillin-allergic patients, it is not a first-line treatment.

Prednisone 30 mg daily for 7 days – Incorrect. Prednisone can be used to treat Jarisch-Herxheimer reactions, which are common in patients with malignant syphilis.

Conflicts of interest

None disclosed.