Secondary Syphilis: The Great Masquerader: A Case Presentation and Discussion Gina Caputo, DO,* Roxanne Rajaii, MS, DO,** Gary Gross, MD,*** Daniel S. Hurd, DO**** *Dermatology Resident, 2nd year, LewisGale Hospital Montgomery/Edward Via College of Osteopathic Medicine, Blacksburg, VA **Osteopathic Intern, Northeast Regional Medical Center, Kirksville, MO ***Clinical Dermatologist, LewisGale Hospital Salem, Salem, VA ****Program Director, Dermatology Residency Program, LewisGale Hospital Montgomery/Edward Via College of Osteopathic Medicine, Blacksburg VA Disclosures: None Correspondence: Gina Caputo, DO; [email protected] Abstract Syphilis has been called “the great imitator” due its wide range of variable symptoms that often mimic other disease processes. The painless syphilis chancre can easily go unnoticed, or be mistaken for a folliculitis, abrasion, or benign papule. The non-pruritic, diffuse rash that develops in secondary syphilis, characterized by dissemination and multiplication of the microorganism in different tissues, typically presents anywhere from simultaneously to six months after the healing of the primary chancre.1 We present a challenging case of secondary syphilis that masqueraded as connective-tissue disease, granuloma annulare, and tinea corporis for years despite initial treatment. Introduction and the importance of accurate diagnosis and performed with a clinical suspicion of a gyrate Syphilis, an entity with origins dating back to the early treatment to prevent progression of syphilis erythema or granuloma annulare. Biopsy showed 1530s, was first formally described in 1905. It is a to cardiovascular and neurologic sequelae. A high superficial and deep perivascular dermatitis with chronic disease with varying presentations and a clinical suspicion of disease, coupled with clinical, abundant perivascular lymphocytes and plasma waxing and waning course. Sexual contact is the serologic, and histologic evidence, is optimal for cells. There was focal patchy vacuolar interface main mode of transmission, with the causative diagnosis and early management of syphilis. change and increased reticular dermal mucin organism being Treponema pallidum, a spirochete. confirmed with Alcian blue/PAS stain (Figures 5 The gold standard of diagnosis is serologic testing, Case Report [4x], 6 [20x]). A 63-year-old Caucasian male with no documented past and penicillin G remains the treatment of choice. medical history presented in April 2015 for evaluation With further interrogation of the patient and review The condition’s varying presentations, along of a pruritic, diffuse rash of seven months’ duration. of the medical record, the patient had been seen with late manifestations of disease that involve The patient denied any constitutional symptoms. in 2010 for a similar rash, also treated with oral numerous organ systems, explain its distinction as 1,2 The patient had diffuse annular, granulomatous, terbinafine and biopsied, with results indicating drug the “great imitator.” erythematous papules coalescing into plaques with eruption versus arthropod-bite reaction. At that Syphilis is commonly misdiagnosed as connective- central clearing on the trunk, back, bilateral biceps and time, an ANA, Lyme titer and RPR were performed. tissue disease, granuloma annulare, lupus vulgaris, forearms (Figures 1-4). The rash was treated with oral The RPR came back positive for syphilis, and the psoriasis, tinea corporis, and other dermatological terbinafine and steroids and initially improved. patient was referred to Infectious Disease. He had diseases. Several case reports in the literature undergone an extensive workup at that time for Four weeks later, the patient returned without highlight the similarities between these diseases Histoplasma, HIV, ANA, Lyme, Blastomyces, and significant improvement, and a punch biopsy was Cryptococcus. The patient was started on cefuroxime 500 mg twice a day for the syphilis. Figure 3 Figure 1 Upon further questioning in 2015, the patient reported he may have been partially treated by the Centers for Disease Control (CDC) for syphilis. Figure 5 Figure 4 Figure 2 Figure 6 CAPUTO, RAJAII, GROSS, HURD Page 48 The patient denied any extramarital affairs. We approximately one-third of patients with untreated non-caseating granulomas on skin biopsy, whose performed another RPR, with a result of 1:128. The primary syphilis develop tertiary syphilis.1,4 lesions were exacerbated by treatment with topical patient was referred to Infectious Disease for work- Cardiovascular symptoms usually present between corticosteroids. Further investigation revealed this up of tertiary syphilis and treatment. Infectious 10 years and 30 years after the initial infection. was not a case of GA but rather tertiary syphilis Disease treated the patient with ceftriaxone 2 g IV The most common cardiovascular manifestation of with neurologic and cardiovascular manifestations.4 every 24 hours for two weeks, and he was worked up disease is syphilitic aortitis, typically involving the again for HIV and hepatitis. He also underwent a ascending aorta.2 Clinical signs and symptoms of Bittencourt et al. report a different case of secondary lumbar puncture to rule out neurosyphilis. Results neurosyphilis include “focal central nervous system syphilis in an HIV patient with palmoplantar from the HIV and hepatitis labs and the lumbar ischemia and stroke, tabes dorsalis (progessive lesions masquerading as palmoplantar psoriasis. puncture were negative. The patient was treated ataxia, bladder incontinence), and general paresis They present a 32-year-old male with “bilateral successfully for secondary syphilis. (altered mental status, depression, forgetfulness, asymptomatic erythematous-scaly plaques on confusion).”4 Cutaneous tertiary syphilis typically palms and soles for three months, associated with Discussion presents with nodular lesions that can easily mimic periungual erythema, subungual hyperkeratosis Syphilis is a chronic disease with varying other dermatologic diseases such as granuloma and onychodystrophy of toenails.” This case presentations and a waxing and waning course. annulare, lupus vulgaris, psoriasis, and sarcoid.4 demonstrates the challenge of diagnosing syphilis, While sexual contact is the main mode of in that clinically, it can mimic psoriasis and transmission, with the causative organism being Diagnosis of syphilis is based on both clinical dermatophytosis. However, the ungual alterations Treponema pallidum, a spirochete, transmission and laboratory findings. The gold standard for typical of syphilis in the case by Bittencourt et across the placenta is thought to be the second the diagnosis of primary syphilis continues to al., coupled with a negative result of mycological most common mode.2,3 Numerous studies have be visualization of spirochetes under dark-field examination and improvement after treatment, led investigated the transmission probability among microscopy. For secondary, latent, and tertiary to the actual diagnosis of syphilis over its mimickers. partners and have estimated it to be around 60 syphilis, serologic testing is the method of choice This validates the importance of clinical suspicion, percent. Three stages of syphilis have been described: for diagnosis. Nontreponemal tests, including particularly in the case of atypical manifestations of The primary stage, presenting with a painless VDRL, are often indicated for screening, while secondary syphilis.3,4 chancre at the site of inoculation; the secondary treponemal tests, including RPR, FTA-ABS (the stage, characterized by a polymorphic rash; and the serum fluorescent treponemal antibody absorption Conclusion tertiary stage, characterized by cardiovascular and test), and MHA-TP (microhemagglutination test Syphilis is a disease that skillfully mimics other neurologic sequelae and gumma formation. The for T. pallidum), are used to confirm the diagnosis. dermatological diseases in both clinical and 6 tertiary stage is the most destructive. Nontreponemal tests, however, can lack sensitivity histologic features. Furthermore, it is a disease with and can give a high rate of false-positive reactions. multisystem effects, one that allows a dermatologist Syphilis is divided into early (< 1 year) and late This is particularly true in patients of increased “to highlight the relationship of skin diseases to the 7 (> 1 year) stages, with the early stages (primary, age, patients who are pregnant or drug-addicted, rest of the body.” The cases by Wu and Bittencourt secondary, and early latent) believed to be infectious. and those with malignancy, autoimmune diseases et al., along with the present case, exemplify this Late manifestations of disease involving all organ (SLE), and viral (EBV and hepatitis), protozoal mimicry and the need for a high clinical index 3,4 systems have given syphilis its name as the “great or mycoplasmal infections. Neurosyphilis is often of suspicion for syphilis. Although a variety of imitator,” with the key to diagnosis remaining a diagnosed based on a combination of results from diagnostic tools are available for accurate diagnosis, 2 high index of suspicion. serologic testing, abnormalities of CSF cell count the incidence of false-negative laboratory tests as and protein levels, or a reactive CSF VDRL. well as clinical features resembling other etiologies A single, painless, indurated ulcer with a clean make it one of the most commonly misdiagnosed base characterizes primary syphilis. These primary The first-line therapy for syphilis