Secondary syphilis and HIV.
Syphilis is a sexually acquired infectious disease that has been the target of many aggressive public health interventions by the US government since the 1940s. Initial intervention resulted in a marked decrease in the incidence of the disease, but in more recent years syphilis has re-emerged. Syphilis frequently presents in tandem with newer conditions such as HIV (1). Because of this more recent association, little knowledge is available about the diagnosis and treatment of syphilis in a patient with concurrent HIV. This case study reviews the disease presentations of syphilis manifesting in a patient with HIV disease.
A 41-year-old white man was admitted to Baylor University Medical Center at Dallas complaining of a diffuse head-to-toe erythematous, papular rash of 3-months' duration. The rash involved all areas of the skin, including the palms, soles, and genitalia. The rash was neither painful nor pruritic and had changed minimally since its onset 2 months earlier. Review of systems was remarkable for fever, chills, sore throat, odynophagia, dry cough, and sinus congestion. His past medical history included HIV diagnosed 25 years earlier (age 16) with an unknown CD4 count. The patient was a nonsmoker, nondrinker, and reportedly had not been sexually active over the past year. He had a history of methamphetamine abuse, but had quit using the substance 6 months earlier. He also had allergies to sulfonamides, penicillin, ciprofloxacin, Bactrim, and amoxicillin.
He had a diffuse erythematous, papular eruption involving the face, trunk, and upper and lower extremities (Figure 1). Discrete papular lesions with minimal scale measured approximately 1 cm and involved the palms and soles (Figure 2) as well as the genitals. No evident lip or buccal mucosal lesions were noted.
His blood work revealed anemia, with hemoglobin levels at 7.9 g/dL and hematocrit levels at 24.1%, an overall lymphocytopenia with a markedly decreased CD4 count (102), and a viral load of 1.43 million. A serum rapid plasma reagin test was positive at a titer >1 to 512, indicating the presence of syphilis infection. The cerebrospinal fluid appeared grossly bloody with a glucose level of 50 mg/100 mL, protein level of 348 mg/ 100 mL, red blood cell count of 42,000, and white blood cell count of 42, with a differential of 28 lymphocytes, 45 neutrophils, 2 basophils, and 4 monocytes. The high white blood cell and neutrophil count was indicative of an active infection, with the low lymphocyte count compatible with his HIV infection. The cerebrospinal fluid Venereal Disease Research Laboratory test was nonreactive, thus ruling out the presence of neurosyphilis. The patient also had a positive tuberculosis QuantiFeron gold test result but a negative subsequent chest x-ray, suggesting an inactive M. tuberculosis infection. The patient tested positive for blastomyces antibody, which suggested previous exposure to Blastomyces dermatitidis. Epstein-Barr virus was detected via polymerase chain reaction. A skin punch biopsy demonstrated chronic dermatitis with positive cell-rich inflammatory reactions containing plasma cells, suggestive of syphilitic dermatitis. Subsequent staining of the skin sample indicated the presence of spirochete organisms.
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A comprehensive analysis of the laboratory data resulted in a diagnosis of secondary syphilis as well as Epstein-Barr virus, Blastomyces exposure, and confirmation of HIV. The patient was administered a 14-day course of 24 million units daily of intravenous penicillin. He was started on highly active antiretroviral therapy and tuberculosis prophylaxis and placed on a 2-week course of valacyclovir, 1 g orally three times daily, for varicella zoster virus. He was also given dapsone 100 mg orally daily as prophylaxis against pneumocystis pneumonia. The patient was instructed to follow up daily at his physician's office for penicillin infusion and further infectious disease workup.
Syphilis is a sexually transmitted disease caused by the spirochete microorganism Treponema pallidum (1). Concomitant syphilis and HIV infection are particularly common among men who have sex with men, intravenous drug abusers, and prostitutes (2). Although syphilis presentation in patients with HIV is largely similar to that in patients without HIV, differences in disease manifestation may be present.
The first stage of syphilis, known as primary syphilis, is marked by the presence of a chancre, a well-demarcated, relatively painless, ulcerated lesion evolving from a papule with resolution within 3 to 6 weeks. Unilateral or bilateral inguinal adenopathy may also be present in primary syphilis (1). Patients infected with both HIV and syphilis show chancres characteristic of primary syphilis, although these chancres may be more numerous, larger, and deeper (3). Chancres as compared to HIV-negative patients are also more likely to persist in to the secondary stage. Our patient, however, did not exhibit any evidence of an active or healed primary chancre.
Secondary syphilis has several symptoms. Patients frequently present with systemic symptoms that include fever, headache, anorexia, weight loss, sore throat, and myalgia. Our patient presented with both a fever and a sore throat. The most characteristic finding in secondary syphilis is that of a diffuse, papular rash that usually covers the torso, extremities, palms, and soles. The lesions are generally 0.5 to 2 cm in diameter with a moderate degree of peripheral (collarette) scale specifically notable on the palms and soles (see Figure 2). Other dermatologic signs include mucosal lesions, condylomata lata, alopecia, and generalized lymphadenopathy (4). Secondary syphilis in patients with concurrent HIV may present with a broad spectrum of cutaneous morphologies, which include papulosquamous, lenticular, annular, and pustular lesions and those resembling eczema, leprosy, and mycosis fungoides (5). In patients with advanced HIV, secondary syphilis may present as malignant secondary syphilis. This is characterized by severe ulcerating lesions and gummatous infiltration of mouth, eye, subcutaneous tissue, bone, joints, and cerebrospinal system (1). Thus, one should be careful to note that secondary syphilis is a disease that is more aggressive in HIV patients. Our patient did not present with any signs of malignant secondary syphilis. In this patient, the rash was diffuse, generalized, erythematous, and papular and covered the entire body, including genitals, palms, and soles (Figures 1 and 2). This unique combination of symptoms in the patient's history is what initially suggested secondary syphilis as a possible diagnosis.
Latent syphilis follows secondary syphilis and is a period of relatively few symptoms and a decreased chance of passing on the infection. As many as 25% of untreated patients in the latent stage will progress to tertiary syphilis, a stage characterized by cardiovascular and neurologic features as well as gummatous lesions (1).
Cardiovascular features of tertiary syphilis, such as coronary otitis, aortic regurgitation, and aortic aneurysm, are the most common of the three tertiary manifestations and develop anywhere from 10 to 30 years after initial infection (1). Previous cases have shown that aortitis may develop more rapidly in HIV-coinfected individuals (3). Gumma formation may begin as soon as a year after infection but is most likely to occur 15 years after the initial infection. Gummatous lesions may form in any organ and can lead to ulcers (1). Neurosyphilis occurring at the tertiary stage is known as late neurosyphilis, while neurosyphilis occurring at the earlier stages is known as early neurosyphilis. During early stages of syphilis, spirochetes infiltrate the central nervous system, resulting in early neurosyphilis which includes such symptoms as meningitis, stroke, seizure, myelopathy, brainstem abnormality, cranial nerve abnormalities, vestibular disease, and ocular disease. Late neurosyphilis primarily involves the brain and spinal cord parenchyma, resulting in dementia, tabes dorsalis, general paresis, sensory ataxia, and bowel or bladder dysfunction (1).
In HIV-negative individuals, confirmatory diagnosis of secondary syphilis is possible through serologic testing; however, in individuals with untreated HIV, as in this case, serologic tests are more likely to be inaccurate. In such cases the serologic tests can be repeated at a later date and/or a skin biopsy can be performed (1). In this case, an ultimate diagnosis of syphilis could be arrived at when the patient tested positive on both a serologic test, rapid plasma reagin, and in the skin biopsy. Penicillin G, at a dose of 2.4 million units intravenously, is the recommended antibiotic in early syphilis. Treatment is followed by a reexamination at 6 and 12 months to ensure a reduction in nontreponemal antibody and thus to confirm a response to treatment. If no such reduction is seen, a follow-up course of benzathine penicillin is administered.
(1.) Zetola NM, Engelman J, Jensen TP, Klausner JD. Syphilis in the United States: an update for clinicians with an emphasis on HIV coinfection. Mayo Clin Proc 2007;82(9):1091-1102.
(2.) Buchacz K, Patel P, Taylor M, Kerndt PR, Byers RH, Holmberg SD,
Klausner JD. Syphilis increases HIV viral load and decreases CD4 cell counts in HIV-infected patients with new syphilis infections. AIDS 2004;18(15):2075-2079.
(3.) Narula T, Kamboj S, Martinez J, Engel LS. Co-infection: HIV and the great mimic syphilis. HIV Clin 2010;22(2):7-10.
(4.) Singh AE, Romanowski B. Syphilis: review with emphasis on clinical, epidemiologic, and some biologic features. Clin Microbiol Rev 1999;12(2):187-209.
(5.) Villasenor-Park J, Clark E, Ho J, English JC 3rd. Folliculotropic nonalopecic secondary syphilis. J Am Acad Dermatol 2011;65(3):686-687.
Shagun Dhaliwal, Mahir Patel, MD, and Alan Menter, MD
From the Texas A&M Health Science Center College of Medicine, Bryan, Texas (Dhaliwal), and the Division of Dermatology, Department of Internal Medicine, Baylor University Medical Center at Dallas (Patel, Menter).
Corresponding author: Alan Menter, MD, Division of Dermatology, Department of Internal Medicine, Baylor University Medical Center at Dallas, 3900 Junius Street, Suite 125, Dallas, Texas 75246 (e-mail: firstname.lastname@example.org).