Syphilis in Dermatology: Recognition and Management.

The incidence of syphilis has been increasing in the USA since 2000. Notably, the coronavirus disease 2019 pandemic negatively impacted the public health efforts to contain the spread of sexually transmitted diseases including syphilis and congenital syphilis. Clinical manifestations of syphilis are predominantly mucocutaneous lesions, thus dermatologists are primed to recognize the myriad presentations of this disease. Primary syphilis is classically characterized by a painless transient chancre most often located in the genital area. Secondary syphilis typically manifests clinically as systemic symptoms in addition to a mucocutaneous eruption of which a variety of forms exist. Although less common in the era of effective penicillin treatment, late clinical manifestations of syphilis are described as well. In addition to recognition of syphilis on physical examination, several diagnostic tools may be used to confirm infection. Treponema pallidum spirochetes may be detected directly using histopathologic staining, darkfield microscopy, direct fluorescent antibody, and polymerase chain reaction assays. A table detailing the histopathologic features of syphilis is included in this article. Serologic testing, non-treponemal and treponemal tests, is the preferred method for screening and diagnosing syphilis infections. Two serologic testing algorithms exist to aid clinicians in diagnosing positive syphilis infection. Determining the correct stage of syphilis infection combines results of serologic tests, patient history, and physical examination findings. Using the current Centers for Disease Control and Prevention case definitions and treatment guidelines, a management algorithm is proposed here. Penicillin remains the pharmacological treatment of choice although specific clinical situations allow for alternative therapies. Syphilis is a reportable disease in every state and should be reported by stage according to individual state requirements. Screening recommendations are largely based upon risks encountered through sexual exposures. Likewise, sexual partner management includes evaluating and treating persons exposed to someone diagnosed with an infective stage of syphilis. Close clinical follow-up and repeat testing are recommended to ensure appropriate response to treatment. This guide will discuss the current epidemiology of syphilis and focus on practice aspects of diagnosis and management, including public health reporting.

[A case of early syphilitic hepatitis with jaundice cured by high-dose amoxicillin and probenecid].

A 44-year-old man was admitted because of general malaise, jaundice, and epigastric pain. The patient had no significant medical history. However, the patient visited a brothel 3 months ago and noticed initial induration on his penis 2 months ago. Physical examination revealed swelling surface lymph nodes in the inguinals. Laboratory examination showed moderate hepatic disorder and jaundice. Hepatitis virus markers and various types of autoantibodies were negative, but serological test for syphilis was positive. The symptoms and abnormal data improved immediately after the patient was treated with amoxicillin (3000mg/day) and probenecid (750mg/day). Thus, a diagnosis of early syphilitic hepatitis was established. In addition, syphilis is not just a genital disease. This disease should be thought of in a patient with liver dysfunction, especially among people of high sexual activity.

Cutaneous Rosai - Dorfman disease in a patient with late syphilis and cervical cancer - case report and a review of literature.

BACKGROUND: Cutaneous Rosai - Dorfman disease (CRDD) is extremely rare variant of idiopathic histiocytic proliferative disorder, which may manifest as a non-specific macules, papules, plaques or nodules ranging in size and colour from yellow - red to red -brown. CASE PRESENTATION: A 52-year-old female presented with three gradually enlarging, reddish - brown nodules on the right upper extremity lasting six months. The patients denied fever, weight loss, malaise. Clinical examination and imaging tests showed no sign of lymphadenopathy. A biopsy specimen of a nodule showed a dense dermal polymorphic infiltrate with numerous histiocytes exhibiting emperipolesis phenomenon. Immunohistochemical staining of the histiocytes showed S-100 protein (+), CD68(+), but CD1a (-). Aforementioned findings were consistent with CRDD characteristics. Additionally, a routine serological screening and confirmatory serological tests for syphilis were positive. Syphilis of unknown duration was diagnosed. The IgG antibodies titre against Chlamydia trachomatis was elevated. An isolated sensory impairment over the right trigeminal nerve was found on neurological consultation. Comprehensive gynaecological assessment was carried out because of patient's complaints of bleeding after sexual intercourse and led to diagnosis of cervical cancer. The initial therapy with methotrexate was discontinued after three months due to neutropenia. Further therapy with dapson was ineffective, therefore complete surgical excision was recommended. CONCLUSIONS: CRDD is a rare, benign condition especially difficult to diagnose due to lack of general symptoms and lymphadenopathy. Histopathologic examination with immunohistochemical staining, exhibiting characteristic and reproducible findings play a key role in establishing an accurate diagnosis. In the presented case activated histiocytes demonstrated in a lesional skin might be a response to immune dysregulation related to chronic, untreated sexually transmitted infections and cancer.

High-dose oral amoxicillin plus probenecid is highly effective for syphilis in patients with HIV infection.

BACKGROUND: Intramuscular benzathine penicillin G (BPG) is widely used for the treatment of syphilis. However, BPG is not available in some countries. This study examined the effectiveness and safety of high-dose oral amoxicillin plus probenecid for the treatment of syphilis in patients with human immunodeficiency virus type 1 (HIV-1). METHODS: This retrospective observational study included 286 HIV-infected male patients with syphilis (median age, 36 years; median CD4 count, 389 cells/µL) who were treated with oral amoxicillin 3 g plus probenecid. Syphilis was diagnosed by both serum rapid plasma reagin (RPR) titers ≥8 and positive Treponema pallidum hemagglutination test. Patients with neurosyphilis diagnosed by cerebrospinal fluid examination were excluded. Successful treatment was defined as a at least 4-fold decrement in RPR titer. RESULTS: The overall treatment efficacy was 95.5% (95% confidence interval [CI], 92.4%-97.7%; 273/286 patients), and efficacy for primary, secondary, early latent, late latent, and unknown duration syphilis was 93.8% (95% CI, 68.1%-99.8%; 15/16), 97.3% (95% CI, 92.9%-99.2%; 142/146), 100% (95% CI, 90.5%-100%; 37/37), 85.7% (95% CI, 58.6%-96.4%; 18/21), and 92.4% (95% CI, 81.9%-97.3%; 61/66), respectively. Treatment duration was mostly 14-16 days (49.7%) or 28-30 days (34.3%), with efficacy of 94.4% (134/142) and 95.9% (94/98), respectively; 96.3% of successfully treated patients achieved a ≥4-fold decrement in RPR titer within 12 months. Adverse events were noted in 28 (9.8%) patients, and 25 of these (89.3%) were successfully treated. Only 6% of patients underwent lumbar puncture. CONCLUSIONS: The combination of oral amoxicillin 3 g plus probenecid was highly effective and tolerable for the treatment of syphilis in patients with HIV-1 infection.

[Rheumatic expression of secondary syphilis]. / Manifestações reumáticas da Sífilis Secundária.

Syphilis is a disease caused by Treponema pallidum infection with protean clinical manifestations. Musculoskeletal complaints are however uncommon and most of the time mild. Occasionally they can dominate the clinical picture and simulate a variety of rheumatic diseases. The authors present the clinical case of a 33-year-old woman who developed a lupus-like syndrome in the postpartum, characterized by polyarthritis, elevated acute phase reactants and positive antinuclear antibodies (ANA). Physical examination revealed a macular non-pruriginous skin rash involving the trunk, upper limbs and palms. The Rapid Plasma Reagin (RPR) and Treponema Pallidum Hemaglutination (TPHA) tests gave a positive result and the patient was diagnosed as secondary syphilis and medicated with 2.4 MU of benzathine penicillin intramuscular weekly for 3 weeks, with complete resolution of clinical signs and ANA negativation. The association of rash and arthritis may occur in several rheumatic diseases but in the presence of palmoplantar involvement, the possibility of syphilis infection should not be overlooked.

High prevalence of sexually transmitted infections in HIV-infected men during routine outpatient visits in the Netherlands.

BACKGROUND: In the Netherlands, no guidelines exist for routine sexually transmitted infection (STI) screening of human immunodeficiency virus (HIV)-infected men having sex with men (MSM). We assessed prevalence and factors associated with asymptomatic STI. METHODS: MSM visiting HIV outpatient clinics of academic hospitals were tested for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), syphilis, and hepatitis B and C infection. Prevalence and risk factors were studied using logistic regression. RESULTS: In total, 659 MSM were included between 2007 and 2008. STI were found in 16.0% of patients, mostly anal CT and syphilis. One new hepatitis B and 3 new hepatitis C infections were identified. In multivariate analyses, any STI (syphilis, CT, or NG) was associated with patient's age below 40 years (odds ratio [OR]: 2.5, 95% confidence interval [CI]: 1.3-5.0), having had sex with 2 or more sexual partners (OR 2.1, 95% CI: 1.2-3.5), the use of the same sexual toys with a sexual partner (OR 2.2, 95% CI: 1.0-4.9), and enema use before sex (OR: 2.3, 95% 1.2-4.2). Syphilis was independently associated with fisting with gloves versus no fisting (OR: 4.9, 95% CI: 1.7-13.7) and with rimming (OR: 5.0, 95% CI: 1.7-15.0). CT or NG were associated with age below 45 years (age 40-44 years: OR: 2.4, 95% CI: 1.1-5.3; age <40 years: OR: 2.4, 95% CI: 1.1-5.4), enema use before sex (OR: 2.4, 95% CI: 1.3-4.4) and drug use during sex (OR: 2.4, 95% CI: 1.4-4.0). CONCLUSIONS: High-risk sexual behavior was very common, and 16% of HIV-infected MSM in HIV care had an asymptomatic STI, mostly anal CT and syphilis. Development of STI screening guidelines is recommended.

[Clinico-epidemiological features and antimicrobial resistance pattern in gonococcal infection]. / Aspecte clinico-epidemiologice si particularitati ale sensibilitatii la antibiotice în infectia gonococica.

AIM: To analyze clinical and epidemiological features in patients with gonococcal infection attended Dermato-Venerology Clinic in Iasi and regional dermato-venerology offices and to evaluate gonococcal antimicrobial resistance pattern. METHODS: The study was carried out on 129 patients clinically diagnosed and bacteriologically confirmed with gonococcal infection who were subsequently submitted to a questionnaire. We studied their demographic characteristics (sex, age, nationality, marital status), clinical features (site of infection, symptoms, concurrent STI, previous history of gonorrhoea) and behavioral aspects (education, number and type of sexual partners, safe sexual practices). RESULTS: We found in our patients a strong association of gonorrhoea with young male individual, poor educational level and with clinical symptoms of urethritis. The level of antimicrobial resistance is higher than in other European countries. CONCLUSIONS: The poor health-seeking behavior, symptoms not specific enough, resistance pattern, lack of accessible and sensitive diagnostic methods lead to undiagnosed and probably mistreated gonorrhoea.

Colitis and gastroparesis associated with syphilis in an HIV-infected person with an undetectable viral load.

We present a patient with fully controlled HIV disease and a normal CD4 count whose initial treatment for syphilis failed. Biopsy-proven syphilitic colitis and severe gastroparesis developed, requiring the insertion of a temporary percutaneous gastrostomy tube. The patient responded to a course of high-dose aqueous crystalline penicillin followed by doxycycline, and he completely recovered. The occurrence of failure of conventional syphilis treatment in HIV-infected patients is discussed.

Syphilitic uveitis in patients infected with human immunodeficiency virus.

BACKGROUND: This work investigates the incidence and clinical features of syphilitic uveitis in patients infected with human immunodeficiency virus (HIV). MATERIAL AND METHODS: We retrospectively reviewed syphilitic uveitis in patients coinfected with HIV that presented at a referral center between July 2001 and November 2003. RESULTS: Twelve patients (20 eyes) were included. The ocular manifestations of syphilis led to the discovery of HIV-1 seropositivity in three patients. All patients were male and homosexual. One patient has been previously treated for syphilis with benzathine penicillin G. One patient presented with anterior uveitis and 11 patients had panuveitis or posterior uveitis. Necrotizing retinitis was noted in seven eyes (35%), posterior placoid chorioretinitis in six eyes (30%) and optic nerve involvement in five eyes (25%). Of nine patients with available cerebrospinal fluid (CSF) studies, seven (77.8%) had CSF abnormalities. Eleven patients were treated with intravenous penicillin G and one with intravenous ceftriaxone sodium. One patient required a second course of antibiotics to control uveitis. Ocular inflammation decreased and visual acuity improved in all nine patients for whom follow-up was available after treatment. CONCLUSION: Manifestations of syphilitic uveitis in HIV-infected patients are multiple, with high frequencies of posterior uveitis, posterior placoid chorioretinitis, necrotizing retinitis and optic nerve involvement. Syphilitic uveitis in HIV-infected patients seems to have a more severe course and may relapse despite high-dose intravenous penicillin therapy.

[Syphilis and pregnancy]. / Syphilis au cours de la grossesse.

Consequences of syphilis for mother, pregnancy, fetus and child are considerable, but preventable. Serological screening must be offered at the first prenatal visit, using both a treponemal (eg. TPHA) and a non treponemal (eg. VDRL or RPR) test. When the results are compatible with any type of active syphilis, treatment is required. The treatment of choice is penicillin: benzathine penicillin G, 2.4 million units intramuscular, repeated one week later, and most authors recommend a third dose if a late latent syphilis is suspected, or in case of coinfection with HIV. Women with a proven penicillin allergy can be desensitized. Alternative therapies, such as macrolids, are less well evaluated. Follow-up during and after therapy must not be neglected. In case of Jarisch-Herxheimer reaction, the mother should be managed on an inpatient basis, and the fetus carefully monitored. The VDRL should be repeated (usually every trimester), and therapy be renewed if there is not a significant decrease in titer. The fetus should be followed by serial ultrasound examinations. Finally, the child must be followed up clinically and biologically, and treated in case of congenital syphilis. The residual risk of adverse outcome is increased in case of reinfection, lack of maternal therapy or incomplete treatment, or when diagnosis and therapy are performed late in pregnancy.

A randomized, double-blind, placebo-controlled trial of single-dose ciprofloxacin versus erythromycin for the treatment of chancroid in Nairobi, Kenya.

A randomized, double-blind, placebo-controlled clinical trial was conducted in Nairobi, Kenya, to compare single-dose ciprofloxacin with a 7-day course of erythromycin for the treatment of chancroid. In all, 208 men and 37 women presenting with genital ulcers clinically compatible with chancroid were enrolled. Ulcer etiology was determined using culture techniques for chancroid, serology for syphilis, and a multiplex polymerase chain reaction for chancroid, syphilis, and herpes simplex virus (HSV). Ulcer etiology was 31% unmixed chancroid, 23% unmixed syphilis, 16% unmixed HSV, 15% mixed etiology, and 15% unknown. For 111 participants with chancroid, cure rates were 92% with ciprofloxacin and 91% with erythromycin. For all study participants, the treatment failure rate was 15%, mostly related to ulcer etiologies of HSV infection or syphilis, and treatment failure was 3 times more frequent in human immunodeficiency virus-infected subjects than in others, mostly owing to HSV infection. Ciprofloxacin is an effective single-dose treatment for chancroid, but current recommendations for empiric therapy of genital ulcers may result in high treatment failure due to HSV infection.

Autogenous vaccine: the best therapy for perianal condyloma acuminata?

PURPOSE: Treatment of perianal condyloma acuminata is frustrating because most treatment options are fraught with high recurrence rates and patient discomfort. We propose that surgical excision followed by vaccination with an autogenous condyloma acuminata vaccine is the most effective therapy available in primary and recurrent perianal condyloma acuminata. METHODS: Eighty-three patients with perianal condyloma acuminata were treated from 1985 to 1992. Treatment was divided for patients as follows: surgical excision, 20; bichloroacetic acid, 10; podophyllin and interferon A, 5; excision followed by autogenous condyloma acuminata vaccination twice weekly using 0.1 ml subcutaneously for three weeks increasing to 1.0 ml subcutaneously for seven weeks, 43. Syphilis was diagnosed in seven patients; two were human immunovirus-positive. All but three patients were male. Of those patients treated with the vaccination protocol, 25 had primary and 18 had recurrent disease. RESULTS: Recurrence rates were: excision alone and bichloroacetic acid, 50 percent; podophyllin and interferon A, 85 percent; whereas only 4.6 percent recurred when treated with excision and vaccination. Mean follow-up was 13 (range, 6-23) months. All patients treated with the vaccination protocol tolerated the full course of therapy. CONCLUSION: We believe that excision of perianal condyloma acuminata followed by autogenous condyloma acuminata vaccination for approximately ten weeks is the most effective and definitive treatment option and, moreover, should be considered in all patients with perianal condyloma acuminata.

Syphilitic osteitis in a patient with secondary syphilis and concurrent human immunodeficiency virus infection.

Destructive bone disease is a well-recognized complication of congenital and tertiary syphilis. Clinically significant osteitis and osteomyelitis are rare complications of primary or secondary syphilis in patients who are not infected with human immunodeficiency virus (HIV). We report a case of an HIV-infected man who presented with symptomatic, left ulnar osteitis as the initial manifestation of secondary syphilis. The patient's clinical course was complicated by a pathological fracture, but he responded to high-dose intravenous penicillin G therapy and surgical intervention. Results of physical examination on follow-up at 15 months were normal, and a serofast (rapid plasma reagin [RPR]) titer of 1:4 and a markedly decreased uptake on bone scintigraphy were observed. Our case report suggests that bone disease can represent an atypical manifestation of early acquired syphilis and that HIV-positive patients who present with orthopedic complaints or bone lesions should be evaluated for the presence of syphilitic bone disease.

The ocular manifestations of syphilis in the human immunodeficiency virus type 1-infected host.

Nine patients with active ocular or optic nerve involvement by syphilis who also had concurrent human immunodeficiency virus type-1 (HIV-1) infection are described. The ocular manifestations of syphilis led to the discovery of HIV-1 seropositivity in four of nine cases. Fifteen eyes were affected. Ocular manifestations were: iridocyclitis in three eyes, vitreitis in one eye, retinitis or neuroretinitis in five eyes, papillitis in two eyes, optic perineuritis in two eyes, and retrobulbar optic neuritis in two eyes. Three patients diagnosed with acquired immune deficiency syndrome (AIDS) had the worst initial visual acuities. Six of nine patients had evidence of concomitant central nervous syndrome (CNS) involvement with syphilis. Benzathine penicillin was administered intramuscularly to three patients. All three had relapses. Seven of nine patients treated intravenously with high-dose penicillin had dramatic responses to therapy with improvement in vision and serologies and no evidence of relapse. Regimens accepted for the treatment of neurosyphilis appear to be adequate for the treatment of ocular syphilis in HIV-1-infected patients though further long-term follow-up will be required.