Malignant syphilis (MS) is a rare form of secondary syphilis with grotesque skin lesions, systemic manifestation and life-threatening complications. This article presents a case of MS in an immunocompetent 41-year-old female, who initially manifested with a generalized nonpruritic erythematous rash and systemic symptoms. She was mistreated for generalized impetigo and hepatitis attributed to chronic alcoholism. After partial recovery and a 3-month latent period, she developed infiltrated plaques with crusts on the trunk, head and neck; pharyngitis and laryngeal lesions; generalized lymphadenopathy and nonspecific systemic symptoms. Serologic tests confirmed syphilis, and cerebrospinal fluid analyses indicated the presence of anti-treponemal antibodies. Urine drug screening was positive for cannabinoids. The polymerase chain reaction from skin biopsy samples identified T. pallidum, confirmed with Warthin-Starry staining. Immunohistochemical analysis was uncharacteristic. Tertiary syphilis, neurosyphilis, ocular syphilis and otosyphilis were excluded. However, the patient was treated for neurosyphilis with benzylpenicillin (18 million IU intravenously daily, 14 days) and corticosteroids. No Jarisch-Herxheimer reaction occurred. Ten months after treatment, residual scars were visible, and 1 year later, she attempted suicide. Since MS can resemble other diseases, it should be suspected in a mentally ill patient with chronic drug abuse, systemic nonspecific manifestations and dermatological abnormalities, including the head and neck region.

UNASSIGNED: Although a rare disease, the incidence of congenital syphilis is on the rise in the US. We report a case of early congenital syphilis in a 1-day-old premature boy with positive Rapid plasma reagin titer, respiratory insufficiency, disseminated intravascular coagulation, and encephalopathy, born to a mother with known syphilis infection. Skin examination showed diffuse truncal petechiae, desquamation of the distal extremities, and violaceous, retiform plaques on the buttocks and lower extremities. A biopsy was performed to rule out an infectious etiology or vasculitis. Histopathologic examination revealed irregular epidermal acanthosis with orthokeratosis and parakeratosis. There were foci of neutrophilic infiltrate forming rare pustules within the stratum corneum and focal intraepidermal eosinophils, neutrophils, and rare dyskeratotic keratinocytes. In the dermis, there was some minimal endothelial swelling with a perivascular, interstitial, and periadnexal infiltrate of lymphocytes, eosinophils, and rare plasma cells. A Treponema pallidum immunostain highlighted spirochetes present within the epidermis and within the eccrine ducts. Penicillin G therapy was administered for 10 days. The infant\'s Rapid plasma reagin titer trended downward until it was negative 6 months after birth. Literature review reveals 8 case reports within the last 20 years describing the histopathology of rashes in congenital syphilis. Herein we summarize the reported histopathology of rashes in congenital syphilis and compare it to the histopathology of rashes in secondary syphilis in adults.

Approximately 1 in 5 adults in the US had a sexually transmitted infection (STI) in 2018. This review provides an update on the epidemiology, diagnosis, and treatment of gonorrhea, chlamydia, syphilis, Mycoplasma genitalium, trichomoniasis, and genital herpes.
From 2015 to 2019, the rates of gonorrhea, chlamydia, and syphilis increased in the US; from 1999 to 2016, while the rates of herpes simplex virus type 1 (HSV-1) and HSV-2 declined. Populations with higher rates of STIs include people younger than 25 years, sexual and gender minorities such as men and transgender women who have sex with men, and racial and ethnic minorities such as Black and Latinx people. Approximately 70% of infections with HSV and trichomoniasis and 53% to 100% of extragenital gonorrhea and chlamydia infections are asymptomatic or associated with few symptoms. STIs are associated with HIV acquisition and transmission and are the leading cause of tubal factor infertility in women. Nucleic acid amplification tests have high sensitivities (86.1%-100%) and specificities (97.1%-100%) for the diagnosis of gonorrhea, chlamydia, M genitalium, trichomoniasis, and symptomatic HSV-1 and HSV-2. Serology remains the recommended method to diagnose syphilis, typically using sequential testing to detect treponemal and nontreponemal (antiphospholipid) antibodies. Ceftriaxone, doxycycline, penicillin, moxifloxacin, and the nitroimidazoles, such as metronidazole, are effective treatments for gonorrhea, chlamydia, syphilis, M genitalium, and trichomoniasis, respectively, but antimicrobial resistance limits oral treatment options for gonorrhea and M genitalium. No cure is available for genital herpes. Effective STI prevention interventions include screening, contact tracing of sexual partners, and promoting effective barrier contraception.
Approximately 1 in 5 adults in the US had an STI in 2018. Rates of gonorrhea, chlamydia, and syphilis in the US have increased, while rates of HSV-1 and HSV-2 have declined. Ceftriaxone, doxycycline, penicillin, moxifloxacin, and the nitroimidazoles are effective treatments for gonorrhea, chlamydia, syphilis, Mycoplasma genitalium, and trichomoniasis, respectively, but antimicrobial resistance limits oral therapies for gonorrhea and Mycoplasma genitalium, and no cure is available for genital herpes.

OBJECTIVE: To systematically evaluate the diagnostic performance of procalcitonin (PCT) and C-reactive protein (CRP) for distinguishing bacterial infections from lupus flares in systemic lupus erythematosus (SLE) via meta-analysis.
METHODS: Electronic databases were comprehensively searched. The pooled standard mean difference (SMD) and 95% confidence interval (CI) were calculated to estimate the differences of serum PCT and CRP levels between bacterial infections and flares in SLE. Sensitivity, specificity and summary receiver operating characteristics (SROC) curve were used to assess the diagnostic values of PCT and CRP. The use of fixed or random effects model depended on heterogeneity.
RESULTS: Fifteen studies were included in the analysis. Serum PCT and CRP levels were significantly higher in SLE patients with bacterial infections compared to SLE patients with flares (PCT: SMD = 1.035, 95 %CI = 0.708 to 1.362; CRP: SMD = 1.000, 95 %CI = 0.758 to 1.242). The overall sensitivity, specificity, area under the SROC curve, positive likelihood ratios (PLR) and negative likelihood ratios (NLR) of PCT were 0.62, 0.88, 0.862, 6.63 and 0.36, respectively, while the same indicators for CRP were 0.72, 0.70, 0.784, 2.45 and 0.38, respectively.
CONCLUSIONS: Serum PCT and CRP levels were significantly increased in SLE with bacterial infections. PCT had a better diagnostic performance than CRP. PCT had a high value of PLR and could serve as a rule-in marker, while CRP testing may result in a high false-positive rate due to low PLR; both markers had a suboptimal value of NLR and are not appropriate for ruling out bacterial infections.

Reactive syphilis serologies are investigated by health departments to determine if they represent new infection, reinfection, or treatment failure. Serologies prioritized for investigation based on nontreponemal test titer and age (using a \"reactor grid\") undergo manual record search and review. We developed a computerized algorithm that automates the record search and review.
We developed and tested the algorithm using a Florida Department of Health data set containing serologies reported January 2016 to December 2018 and previous records linked to each individual. The algorithm was based on the syphilis case definition, which requires (except primary cases with signs and symptoms) (1) a positive treponemal test result and a newly positive nontreponemal test result or (2) a 4-fold increase in nontreponemal test titer. Two additional steps were added to avoid missing cases. New York City Department of Health and Mental Hygiene validated this algorithm.
The algorithm closed more investigations (49.9%) than the reactor grid (27.0%). The algorithm opened 99.4% of the individuals investigated and labeled as cases by the health department; it missed 75 cases. Many investigations opened by the algorithm were closed by the reactor grid; we could not assess how many would have been cases. In New York City, the algorithm closed 70.9% of investigations, likely because more individuals had previous test in the database (88.2%) compared with Florida (56.5%).
The automated algorithm successfully searched and reviewed records to help identify cases of syphilis. We estimate the algorithm would have saved Florida 590 workdays for 3 years.

Penicillin is the conventional treatment for all stages of syphilis, including ocular and neurosyphilis, according to the recommendations by the Centre for Disease Control and Prevention Sexually Transmitted Disease. This case series highlighted three cases of ocular syphilis which showed prompt treatment response as early as 24 h after the adjunctive intravitreal ceftazidime injection.
Case Series.
In case 1, there was significant improvement in the vision and vitritis after 24 h of a single intravitreal ceftazidime injection. In case 2, the patient achieved his best vision after a total of three intravitreal injections in his left eye and one in his right eye. In case 3, there was a further resolution of perivascular sheathing and retinal haemorrhages seen 1 week after a single intravitreal ceftazidime injection.
The efficacy of intravitreal ceftazidime injection as a local adjunctive therapy in ocular syphilis treatment is noteworthy. It can be considered in cases which show suboptimal or slower treatment response despite early commencement of systemic penicillin to prevent devastating ocular sequelae.

Mother-to-child transmission of syphilis remains a leading cause of neonatal death and stillbirth, disproportionally affecting women in low-resource settings where syphilis prevalence rates are high and testing rates low. Recently developed syphilis point-of-care tests (POCTs) are promising alternatives to conventional laboratory screening in low-resource settings as they do not require a laboratory setting, intensive technical training and yield results in 10-15 minutes thereby enabling both diagnosis and treatment in a single visit. Aim of this review was to provide clarity on the benefits of different POCTs and assess whether the implementation of syphilis POCTs is associated with decreased numbers of syphilis-related adverse pregnancy outcomes.
Following the PRISMA guidelines, three electronic databases (PubMed, Medline (Ovid), Cochrane) were systematically searched for intervention studies and cost-effectiveness analyses investigating the association between antenatal syphilis POCT and pregnancy outcomes such as congenital syphilis, low birth weight, prematurity, miscarriage, stillbirth as well as perinatal, fetal or infant death.
Nine out of 278 initially identified articles were included, consisting of two clinical studies and seven modelling studies. Studies compared the effect on pregnancy outcomes of treponemal POCT, non-treponemal POCT and dual POCT to laboratory screening and no screening program. Based on the clinical studies, significantly higher testing and treatment rates, as well as a significant reduction (93%) in adverse pregnancy outcomes was reported for treponemal POCT compared to laboratory screening. Compared to no screening and laboratory screening, modelling studies assumed higher treatment rates for POCT and predicted the most prevented adverse pregnancy outcomes for treponemal POCT, followed by a dual treponemal and non-treponemal POCT strategy.
Implementation of treponemal POCT in low-resource settings increases syphilis testing and treatment rates and prevents the most syphilis-related adverse pregnancy outcomes compared to no screening, laboratory screening, non-treponemal POCT and dual POCT. Regarding the benefits of dual POCT, more research is needed. Overall, this review provides evidence on the contribution of treponemal POCT to healthier pregnancies and contributes greater clarity on the impact of diverse diagnostic methods available for the detection of syphilis.

BACKGROUND: Septic cardiomyopathy has been observed in association with influenza, indicating that not only bacteria but also other infective agents can cause this condition. There has been no systematic study as to whether Treponema pallidum infection induces septic cardiomyopathy, and we are the first to report this possibility.
METHODS: We report two cases of a 48-year-old man and a 57-year-old man who were diagnosed with syphilis-related septic cardiomyopathy. The diagnosis of cardiomyopathy was made based on elevation of cardiogenic markers and decrease in ejection fraction evaluated by echocardiography. Screen for infective pathogens was negative except for syphilis, which supported our diagnosis. The two patients recovered following effective anti-syphilis treatment and advanced life support technology. Syphilis serology became negative after treatment.
CONCLUSIONS: Syphilis has the potential to cause septic cardiomyopathy. Clinicians should consider Treponema pallidum in cases of septic cardiomyopathy with unknown pathogens. However, the specific pathophysiological mechanism of syphilis-associated septic cardiomyopathy has not been elucidated, and more specific studies are needed.

The articles in this supplement address key questions on syphilis diagnostics, provide reference tables of test performances, and discuss optimal specimens and knowledge gaps. Laboratory-developed genetic direct detection tests could be most useful at the point of care and add to the currently available serologic methods of nontreponemal and treponemal tests.

We reviewed relevant syphilis diagnostic literature and conducted a meta-analysis to address the question, \"What is the sensitivity and specificity of the Syphilis Health Check, a rapid qualitative test for the detection of human antibodies to Treponema pallidum.\" The Syphilis Health Check is the only rapid syphilis test currently cleared by the Food and Drug Administration (FDA). We conducted a systematic review and a meta-analysis using Bayesian bivariate random-effects and fixed-effect models to create pooled estimates of sensitivity and specificity of the Syphilis Health Check. We identified 5 test evaluations published in the literature and 10 studies submitted to the FDA and for a Clinical Laboratory Improvement Amendments waiver application. The pooled sensitivity (95% CI) from the laboratory evaluations (n = 5) was 98.5% (92.1-100%), while pooled specificity was 95.9% (81.5-100.0%). The pooled sensitivity for prospective studies (n = 10) was 87.7% ( 71.8-97.2%), while pooled specificity was 96.7% (91.9-99.2%). Using nontreponemal supplemental testing, the sensitivity improved to a pooled sensitivity of 97.0% (94.8-98.6%). The Syphilis Health Check may provide accurate detection of treponemal antibody.