Global Health: Case Series

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The adult Patient who presents with a rash in Tanzania

Imagine you are a provider working in a rural clinic in Tanzania near Lake Victoria...

A young male presents to your free standing clinic in rural Tanzania for evaluation of general fatigue and rash. He describes approximately three weeks of progressively worsening fatigue, intermittent subjective fever, and a new rash. He states that the rash is located on his palms and is also scattered throughout his chest, abdomen, and back. He denies having any symptoms similar to this before, denies any temporal pattern to his intermittent subjective fevers and states that he sleeps under a mosquito net each evening.  

Image of the patient's rash on the palmer aspect of his left hand. Image was taken with the patient's permission.

Image of the patient's rash on the palmer aspect of his left hand. Image was taken with the patient's permission.

On social history the patient states that he has two wives and that he is sexually active. He states that he has been seen at a clinic once before for penile discharge and was treated at that time, although he cannot recall what medications he was given. Review of systems reveals that the patient also has a lesion on his oral mucosa. He denies any penile discharge currently.

Vital Signs: Temp 99.5 F, HR 85 bpm, BP 110/65 mmHg, RR 15/min

General: Young African male in no acute distress
HEENT: Atraumatic. No scleral icterus. Poor dentition with a few missing teeth. There is a single ulcerated lesion to the oral mucosa of the lower lip. 
Cardiac: Regular rate and rhythm with strong distal pulses
Pulmonary: Clear to auscultation bilaterally
Abdominal: Soft, nontender, nondistended, no palpable hepato/splenomegaly
Skin: There are scattered hyperpigmented lesions to bilateral palms. Similar lesions are observed on bilateral upper extremities, chest, abdomen, and back. 
Neuro: Alert and oriented x 4. He is able to follow all commands. Strength and sensation is grossly intact in the bilateral upper and lower extremities, no dysmetria, gait is ataxic.
Genitourinary: Normal appearing external male genitalia. There are no lesions visualized. There is no discharge from the urethral meatus.  There is no testicular or epidydimal tenderness.

+ What is the Most Likely Diagnosis

SECONDARY SYPHILIS

Syphilis is a sexually transmitted disease caused by the spirochete Treponema pallidum. Clinical manifestations are divided into four stages; primary, secondary, latent, and tertiary, based upon the onset of infection and symptoms present. Classically, a patient with untreated syphilis will progress in a step wise fashion through the stages of the disease. Humans are the only reservoir for Treponema pallidum and infection occurs either through sexual contact or via maternal-fetal transmission [1].

In 2016, the Center for Disease Control (CDC) reported over 27,000 report cases of primary and secondary syphilis in the United States. Rates are highest among persons aged 25-29 years-old, men who report having sex with men, and African Americans [2]. The World Health Organization (WHO) estimated that in 2008 there were approximately 10.6 million new cases of syphilis worldwide. The WHO estimates that in Africa, the incidence of syphilis is 8.5 in females and 9.4 in males per 1000 people [3].

Dark-field microscopy to directly visualize spirochetes remains a high-yield diagnostic tool for primary syphilis and any ulcerative manifestations that may occur in the later stages. This is because the ulcerative lesions are ladened with spirochetes. Classically, a non-treponemal assay, such as VDRL or RPR (sensitivity approx. 78-86%, specificity 85-99%), is performed initially as a screening test. All positive results must then undergo a confirmatory treponemal assay such as FTA-ABS (sensitivity 84% in primary and 100% in all later stages, specificity 96%) [4]. Unfortunately, in rural clinics these assays are generally not available due to their cost as well as the need for refrigeration of the testing reagents. This greatly limits clinics from reliably being able to screen for syphilis. If testing is not available, it may be justified to empirically treat high risk patients who present with clinical symptoms consistent with syphilis because of the sequele untreated syphilis. In areas where testing is available, the CDC recommends repeat testing 6-12 months after treatment to evaluate for treatment response [6].

Typically, the first manifestation of syphilis is a single, painless, indurated, clean-based ulcer on the external genitalia. The chancre can persist anywhere from ten to ninety days but on average will resolve in three weeks [4]. In a study evaluating sensitive and specificity of physical exam in diagnosing primary syphilis, chancroid, and herpes the authors report the sensitivity of physical exam alone (single, painless, indurated, clean-based ulcer) to be only 31%. Therefore, it remains important to consider a broad differential diagnosis when encountering a patient with ulcerative genital lesions [5].

If left untreated, patients will begin to exhibit signs of secondary syphilis after approximately three to five months. During this time there is systemic spread of the spirochetes from the isolated genital lesions to the rest of the body. Classically, patients will present with a non-pruritic rash that is diffuse and involves the palms and soles. Patients can also present with oral/genital ulcerative lesions or with wart-like lesions, termed condyloma lata. Other organ systems can also be affected including renal (glomerulonephritis), liver (hepatitis), CNS (meningitis, headache, iritis, uveitis), and musculoskeletal system (arthritis, osteitis). Constitutional symptoms such as fever, malaise, lymphadenopathy, and weight loss are also common [4].

Some patients with secondary syphilis will experience remission of symptoms spontaneously without treatment. However, in some patients who are appropriately treated they will still not clear the infection completely. In both of these cases, patients then enter latent syphilis, which is characterized by an asymptomatic period. This group is subdivided into “early” and “late” based on disease onset. Those with known exposure or symptoms within one year are considered early onset latent syphilis and those with exposure beyond one year are considered late onset latent syphilis. It is important to designate early or late onset latent syphilis correctly because it has implications on a patient's treatment [4].

Tertiary syphilis is the most destructive stage of syphilis and has devastating consequences. There are three classifications of tertiary syphilis: gummatous syphilis, cardiovascular syphilis, and neurosyphilis. Gummatous syphilis manifests as large granulomatous lesions that cause localized tissue destruction. Most commonly these affect the skin, mucous membranes, and bones, but can affect any other organ systems. Cardiovascular syphilis involves destruction of the elastic tissue of the aorta often resulting in aortitis and aneurysm formation. Neurosyphilis most commonly presents without symptoms; however, can manifest as seizures, hearing loss, or as Tabes Dorsalis, a demyelination of the neural tracts of the dorsal columns resulting in a loss of proprioception, weakness, and diminished reflexes [4].

The CDC recommends all patients with primary syphilis, secondary syphilis, or early latent syphilis be treated with a single dose of 2.4 million units Benzathine Penicillin G intramuscularly. Patients with late latent or tertiary syphilis are recommended to undergo treatment with 2.4 million units of Benzathine Penicillin G intramuscularly three times a week [6]. In penicillin allergic patients, doxycycline 100mg twice a day for two weeks or tetracycline 500mg four times a day for two weeks are the recommended alternatives. For pregnant patients with an established penicillin allergy, it is recommended to desensitize the patient to penicillin and then proceed with administration of penicillin. The rationale for treating all pregnant women with penicillin is that the risk of maternal-fetal transmission causing congenital syphilis is very high and the established regimen, penicillin, is the preferred treatment [7].

This case highlights the challenges that many patients in developing areas face in establishing regular screening and management of curable diseases. Health literacy and financial limitations only further compound this issue. It was truly a humbling and inspiring experience to be able to care for this community of patients. Working in a resource-limited environment highlighted the importance of a thorough history and physical exam.

Authored By H. Gerard Colmer, MD

Posted BY Grace Lagasse, MD