Painful rash with hoarseness: an atypical presentation of syphilis

Abstract

Syphilis is a sexually transmitted disease that can affect multiple organ systems, with central nervous system involvement at any stage. We present a 53-year-old woman with an unusual truncal rash with painful anogenital lesions, accompanied by patchy alopecia, oral lesions, photophobia and hoarseness. She was found to have positive serological tests for syphilis with cerebrospinal fluid findings suggestive of neurosyphilis. She underwent a 14-day course of intravenous penicillin G and exhibited successful resolution of painful anogenital lesions as well as marked improvement in dermatological, oropharyngeal, laryngeal, and neurological symptoms.

Background

Primary and secondary syphilis incidence is on the rise in Western Europe and the USA.^{1 2} In 2017 in the UK alone, there were 7137 new diagnoses of syphilis reported, a 20% increase from 5955 new cases in 2016 and a 148% increase from 2874 new cases in 2008.² In this context, it is important that providers be aware of the diverse presentations of syphilis. Although syphilis has long been considered ‘the great mimicker’ of diseases, there is scarcity in the reporting of atypical presentations. In this report, we present an unusual case of painful syphilitic rash with atypical distribution associated with oropharyngeal, laryngeal and neurological symptoms. It is important to recognise its myriad of unusual presentations, as well as understand its nearly universal response to penicillin treatment.

Case presentation

A 53-year-old woman currently experiencing homelessness with no known medical history presents with 6 weeks of progressive pruritic truncal rash and painful vulvar and peri-anal lesions associated with progressive dysphonia and hair loss of similar onset. She stated that she first noticed a maculopapular rash on her abdomen that spread to her back and groin area over the span of about a month, with papilloma-like lesions noted on her vulva and perianal region that have become progressively painful over the past 3 weeks.

She presented to an outside hospital 1 week before admission, where she was suspected of having acute varicella infection and was sent out with acyclovir. Her rash continued to progress despite treatment with acyclovir—she presented to our hospital 1 week later for increased peri-anal pain and spread of the rash to her chest with no involvement of the extremities, shoulders, neck and head. She denied any fevers, chills, cough, sore throat, recent sick contacts, or any exacerbating or alleviating factors. She did report headaches as well as mild photophobia for the past several weeks, but denied any neck pain, abdominal pain, numbness, or weakness. She denied vision changes, vision blurriness, eye pain, eye redness, or purulent discharge. She denied any medical history or current medications, including herbal supplements. She had been homeless for the past 9 years, with intermittent access to temporary housing and showers. Her social history was significant for 80 pack-year history (started smoking at age 8) and social alcohol use. She denied any history of intravenous drug use and denies any recent sexual activity—her last reported sexual encounter including oral, vaginal, or anal sex was 23 years ago.

On physical examination, the patient was afebrile and haemodynamically stable with a normal cardiovascular and pulmonary examination. The patient had an erythematous, non-confluent maculopapular rash with scattered vesicles over her abdomen, flanks and mid-thoracic back which was mildly tender to palpation (figure 1). Her truncal rash did not follow a dermatomal pattern and there was no involvement of the palms and soles. She also had multiple flesh-coloured plaques with superimposed erosions and dried purulent material covering her vulva, perineum and peri-anal regions that were exquisitely tender to touch. (figures 1 and 2). The patient had significant hoarseness. Her conjunctiva was normal appearing, and the pupils were reactive to light and accommodation. The patient declined a fundoscopic examination and thus was not performed at presentation. Patchy alopecia was noted on the patient’s scalp (figure 3). Examination of the hard palate shows a 0.3 cm oval, flesh coloured patch with no overlaying scale or purulence but with a small amount of early central ulceration (figure 4). The remainder of the examination was unremarkable.

Figure 1.

Clinical image showing maculopapular rash of scattered vesicles over her abdomen and flanks, as well as inflammation of vulvar area with multiple erythematous and flesh-coloured lesions.

Figure 2.

Clinical image demonstrating multiple painful lesions with superimposed erosions and dried purulent material covering the perineum and peri-anal regions.

Figure 3.

Clinical image showing patchy alopecia on the patient’s scalp.

Figure 4.

Clinical image depicting 0.3 cm oval, gummatous, flesh-coloured patch with no overlaying scale or purulence but with a small amount of early central ulceration.

Investigations

Serological testing was non-reactive for varicella zoster, herpes zoster, hepatitis A, hepatitis B, and HIV. Hepatitis C virus (HCV) antibody was reactive, with undetectable HCV RNA by PCR. Antinuclear antibody screen was also negative. Rapid plasma reagent (RPR) screen was positive with a titre of 1:128. Syphilis IgG antibody was also positive. Blood and urine cultures were negative. Given this patient’s headache and photophobia in the context of a positive RPR, lumbar puncture was performed. Cerebrospinal fluid (CSF) showed pleocytosis with increased polymorphonuclear neutrophils and slightly elevated protein to 46 with positive CSF Venereal Disease Research Laboratory (VDRL) testing, consistent with neurosyphilis. Bacterial and fungal blood and urine cultures remained negative throughout her hospitalisation.

Given the patient’s recent onset of hoarseness and significant smoking history, a CT of the neck and chest was done to assess for occult malignancy. Her CT showed soft tissue alterations of her left piriform sinus and was recommended for direct visualisation to exclude submucosal mass or neoplasm. At that point, otolaryngology was consulted to assess nasopharyngeal anatomy. Bedside nasopharyngoscopic examination showed what appeared to be several condylomas present on and adjacent to the patient’s larynx, likely secondary to either human papilloma virus or Treponema pallidum infection. The patient declined biopsies at presentation.

Differential diagnosis

Secondary syphilis with condyloma lata and neurological involvement.

Condyloma accuminata with subsequent viral exanthem.

Ocular syphilis.

Scabies.

HIV.

Herpes simplex.

Pityriasis rosea.

Drug-related reaction.

Treatment

The patient was treated with a 14-day course of intravenous penicillin G per the Centers for Disease Control (CDC) Sexually Transmitted Disease Treatment Guidelines.³ She also received one dose of intramuscular penicillin G benzathine (bicillin) 2.4 million units before discharge, which is also an CDC endorsed option following intravenous penicillin.

Outcome and follow-up

On completion of intravenous antibiotic therapy, the patient’s anogenital lesions and truncal rash had largely resolved with minimal residual closed erythematous macules on her abdomen. The patient had full resolution of pain with near resolution of the peri-anal and vulvar lesions. Additionally, her alopecia and hoarseness resolved. The patient will undergo serial RPR titre checks at 6, 12 and 24 months post-therapy.

Discussion

This case illustrates an unusual presentation of secondary syphilis with concomitant neurological involvement. Her painful, vesicular rash without involvement of the palms or soles was atypical, as were the laryngeal lesions with associated hoarseness. The initial rash described at the outside hospital was vesicular and attributed to possible varicella-zoster infection, even with involvement of the anogenital area. Although this seemed like a reasonable assumption, the presence of hoarseness, headache and photophobia would be unusual. Initially, the exquisite anogenital pain that the patient experienced placed syphilis lower on the differential due to the commonly taught concept that syphilitic lesions are not painful. The notion of syphilis presenting as only non-tender lesions has been challenged in recent literature—one cross-sectional study by Towns et al found that out of 183 men with PCR-positive primary syphilis, about half of the men had a painful primary lesion and about one-third had multiple lesions.^4–7 The lack of involvement of the palms and soles was also unusual for the classically described rash of secondary syphilis. However, the presence of mucocutaneous involvement with condyloma lata is quite characteristic of secondary syphilis.

Interestingly, the concomitant presence of neurosyphilis is a good reminder that neurological involvement can occur at any stage of syphilis.^{8 9} Similarly, although isolated photophobia would be an atypical manifestation of ocular syphilis, clinicians should consider ocular syphilis in any patient presenting with ocular or visual changes. Though no fundoscopic examination was performed at presentation, the patient presented with normal pupillary light reflexes, non-injected conjunctiva, no eye pain and no visual acuity changes, making typical manifestations of ocular syphilis such as keratitis or uveitis less likely. If this patient had been found to have ocular syphilis, however, the treatment would have remained the same 14-day course of intravenous penicillin.³ In treating the patient’s known neurosyphilis, adequate treatment was also provided for any unlikely but technically possible ocular syphilis.

There have been a small number of case reports published about both syphilis related tonsillitis¹⁰ and laryngitis,¹¹ as well as a laryngeal nodule high suggestive of neoplasm,¹² all found to be T. pallidum and successfully treated with penicillin. A search of the literature at initial presentation yielded this information and was helpful in guiding differential as well as indicating work-up of T. pallidum infection.

Learning points.

• Given this patient’s headache and photophobia in the context of a positive rapid plasma reagent, it is important to test for syphilitic involvement of the central nervous system (CNS). Cerebrospinal fluid (CSF) in this case was found to have marked pleocytosis, elevated protein and positive VDRL consistent with neurosyphilis.

• It is important to note that neurosyphilis can happen at any stage (primary, secondary, or tertiary). Neurosyphilis is distinct from tertiary syphilis, which typically refers to gummas, late neurosyphilitic features and cardiovascular involvement. Although this patient had evidence of what might be considered a single gumma (figure 4), her lack of significant neural deficits such as tabes dorsalis, general paresis and Argyll-Robertson pupil made late neurosyphilis (commonly associated with tertiary syphilis) less likely. Regardless of her syphilitic staging, she should be treated with the same 14-day course for neurosyphilis per Centers for Disease Control guidelines.

• As Treponema pallidum can sequester itself into sites such as the CNS and aqueous humour for months to years, it is important to select appropriate penicillin preparation. For any patient found to have CSF abnormalities suggestive of neurosyphilis, treatment with intravenous penicillin G should be given for 10–14 days.