Benzathine Penicillin G Shortage and Secondary Syphilis.

Syphilis is a sexually transmitted infection caused by the bacterium Treponema pallidum. This disease is characterized by four different stages, each presenting with a variety of manifestations or asymptomatic disease. These stages can be further broken down into early-stage syphilis, which includes primary and secondary syphilis, and late-stage syphilis, which includes tertiary syphilis. It is crucial to recognize and treat syphilis early because the later stages of the disease are marked by irreversible damage to the central nervous system (CNS) and cardiovascular system, and can even increase mortality risk. The primary recommended treatment for early-stage syphilis is intramuscular (IM) benzathine penicillin G (BPG). In this case report, we present a patient with secondary syphilis who exhibited red papules and nonspecific skin eruptions. Due to the unavailability of BPG, the patient initially received doxycycline as an alternative treatment. After eight days of searching multiple facilities and pharmacies, a dose of BPG was finally located and administered to the patient. We highlight crucial information about the BPG shortage, including supply and demand challenges, infrastructure issues, and the broader impact on numerous other antimicrobials. We emphasize the importance of recognizing this issue and provide alternatives for managing the disease in resource-limited settings.

[Translated article] AEDV Expert Consensus for the Management of Syphilis.

Syphilis -the "great simulator" for classical venereologists-is re-emerging in Western countries despite adequate treatment; several contributing factors have been identified, including changes in sexual behaviour, which won't be the topic of this article though. In 2021, a total of 6613 new cases of syphilis were reported in Spain, representing an incidence of 13.9×100 000 inhabitants (90.5%, men). Rates have increased progressively since 2000. The clinical presentation of syphilis is heterogeneous. Although chancroid, syphilitic roseola and syphilitic nails are typical lesions, other forms of the disease can be present such as non-ulcerative primary lesions like Follmann balanitis, chancres in the oral cavity, patchy secondary lingual lesions, or enanthema on the palate and uvula, among many others. Regarding diagnosis, molecular assays such as PCR have been replacing dark-field microscopy in ulcerative lesions while automated treponemal tests (EIA, CLIA) are being used in serological tests, along with classical tests (such as RPR and HAART) for confirmation and follow-up purposes. The interpretation of these tests should be assessed in the epidemiological and clinical context of the patient. HIV serology and STI screening should be requested for anyone with syphilis. Follow-up of patients under treatment is important to ensure healing and detect reinfection. Serological response to treatment should be assessed with the same non-treponemal test (RPR/VDRL); 3-, 6-, 12-, and 24-month follow-up is a common practice in people living with HIV (PLHIV). Sexual contacts should be assessed and treated as appropriate. Screening is advised for pregnant women within the first trimester of pregnancy. Pregnant women with an abortion after week 20 should all be tested for syphilis. The treatment of choice for all forms of syphilis, including pregnant women and PLHIV, is penicillin. Macrolides are ill-advised because of potential resistance.

Treponema pallidum Periplasmic and Membrane Proteins Are Recognized by Circulating and Skin CD4+ T Cells.

BACKGROUND: Histologic and serologic studies suggest the induction of local and systemic Treponema pallidum-specific CD4+ T-cell responses to T. pallidum infection. We hypothesized that T. pallidum-specific CD4+ T cells are detectable in blood and in the skin rash of secondary syphilis and persist in both compartments after treatment. METHODS: Peripheral blood mononuclear cells collected from 67 participants were screened by interferon-γ (IFN-γ) ELISPOT response to T. pallidum sonicate. T. pallidum-reactive T-cell lines from blood and skin were probed for responses to 89 recombinant T. pallidum antigens. Peptide epitopes and HLA class II restriction were defined for selected antigens. RESULTS: We detected CD4+ T-cell responses to T. pallidum sonicate ex vivo. Using T. pallidum-reactive T-cell lines we observed recognition of 14 discrete proteins, 13 of which localize to bacterial membranes or the periplasmic space. After therapy, T. pallidum-specific T cells persisted for at least 6 months in skin and 10 years in blood. CONCLUSIONS: T. pallidum infection elicits an antigen-specific CD4+ T-cell response in blood and skin. T. pallidum-specific CD4+ T cells persist as memory in both compartments long after curative therapy. The T. pallidum antigenic targets we identified may be high-priority vaccine candidates.

A Case of Perianal Annular Rash: Atypical Presentation of Recurrent Secondary Syphilis.

Syphilis is a complex, systemic infectious disease caused by Treponema pallidum subspecies pallidum. Secondary syphilitic lesions typically manifest within 3 months following initial exposure to T. pallidum. The predominant cutaneous manifestations of secondary syphilis are macula and papule. Certain individuals with syphilis may present with an atypical rash during the secondary stage owing to immunosuppression and other factors. Herein, we report a rare case of atypical recurrent secondary syphilis around the anus in a 65-year-old woman. Based on cerebrospinal fluid findings and skin biopsy results, the patient was ultimately diagnosed as neurosyphilis and recurrent secondary syphilis. Following intravenous antibiotic therapy, the patient's rash improved significantly. This case underscores the importance for physicians to remain vigilant regarding the possibility of syphilis when encountering cases exhibiting unusual clinical manifestations, as a definitive diagnosis necessitates a comprehensive evaluation.

Syphilitic Stomatitis: Raising Awareness on an Often-Overlooked Presentation of Secondary Syphilis.

Syphilis, a disease caused by the bacteria Treponema pallidum, has a multitude of clinical manifestations and is classified into primary syphilis, secondary syphilis and tertiary syphilis, based on clinical presentations and the time elapsed since the primary infection. The secondary stage of the disease can affect multiple organs and systems, and some of these involvements may be general and non-specific, justifying its name as 'the great imitator'. We present a case of a 30-year-old woman with a history of painful neck lymph nodes with progressive enlargement, persistent headache, weight loss, myalgia and alopecia. During investigations, stomatitis on the dorsal face of the tongue developed. A secondary study showed serum positive for rapid plasma reagin (RPR) and T. pallidum haemagglutination (TPHA), negative RPR in cerebrospinal fluid and normal MRI, thus the diagnosis of secondary syphilis was made. The patient was treated with a single dose of penicillin with complete resolution of symptoms. The case highlights the need for an exhaustive clinical examination, especially in cases presenting with non-specific and general symptoms, and raises awareness for this disease which has increased its prevalence in the last decades. LEARNING POINTS: Syphilis is a resurgent infection with increasing prevalence, and its manifestations in the secondary stage of the disease are general and non-specific, being able to affect every organ system.The oral mucosa may be involved at any stage of the disease and the tongue, often a neglected organ, can be particularly affected and should be routinely observed.The internist, integrating a cornerstone speciality able to manage and diagnose systemic diseases, must be aware of the individual aspects of the physical examination, notably the appreciation and interpretation of each clue and sign found.

AEDV Expert Consensus for the Management of Syphilis. / Documento de expertos de la AEDV para el manejo de la sífilis.

Syphilis -the "great simulator" for classical venereologists-is re-emerging in Western countries despite adequate treatment; several contributing factors have been identified, including changes in sexual behaviour, which won't be the topic of this article though. In 2021, a total of 6613 new cases of syphilis were reported in Spain, representing an incidence of 13.9×100 000 inhabitants (90.5%, men). Rates have increased progressively since 2000. The clinical presentation of syphilis is heterogeneous. Although chancroid, syphilitic roseola and syphilitic nails are typical lesions, other forms of the disease can be present such as non-ulcerative primary lesions like Follmann balanitis, chancres in the oral cavity, patchy secondary lingual lesions, or enanthema on the palate and uvula, among many others. Regarding diagnosis, molecular assays such as PCR have been replacing dark-field microscopy in ulcerative lesions while automated treponemal tests (EIA, CLIA) are being used in serological tests, along with classical tests (such as RPR and HAART) for confirmation and follow-up purposes. The interpretation of these tests should be assessed in the epidemiological and clinical context of the patient. HIV serology and STI screening should be requested for anyone with syphilis. Follow-up of patients under treatment is important to ensure healing and detect reinfection. Serological response to treatment should be assessed with the same non-treponemal test (RPR/VDRL); 3-, 6-, 12-, and 24-month follow-up is a common practice in people living with HIV (PLHIV). Sexual contacts should be assessed and treated as appropriate. Screening is advised for pregnant women within the first trimester of pregnancy. Pregnant women with an abortion after week 20 should all be tested for syphilis. The treatment of choice for all forms of syphilis, including pregnant women and PLHIV, is penicillin. Macrolides are ill-advised because of potential resistance.

Secondary syphilis presenting with alopecia and leukoderma in a stable HIV-positive patient in a resource-limited setting: a case report.

BACKGROUND: Syphilis is an infection caused by the bacteria Treponema pallidum. It is mainly transmitted through oral, vaginal and anal sex, in pregnancy and through blood transfusion. Syphilis develops in primary, secondary, latent and tertiary stages and presents with different clinical features at each stage. Infected patients can remain asymptomatic for several years and, without treatment, can, in extreme cases, manifest as damage in several organs and tissues, including the brain, nervous tissue, eyes, ear and soft tissues. In countries with a high human immunodeficiency virus (HIV) burden, syphilis increases the risk of HIV infections. We report the case of a young HIV-positive black woman who presented with alopecia and hypopigmentation as features of secondary syphilis. CASE PRESENTATION: A virologically suppressed 29-year-old woman on Anti-retroviral Therapy (ART) presented with a short history of generalized hair loss associated with a non-itchy maculopapular rash and skin depigmentation on the feet. Limited laboratory testing confirmed a diagnosis of secondary syphilis. She was treated with Benzathine Penicillin 2.4MU. After receiving three doses of the recommended treatment, the presenting features cleared, and the patient recovered fully. CONCLUSION: This case demonstrates the importance of a high index of clinical suspicion and testing for syphilis in patients presenting with atypical clinical features of secondary syphilis, such as hair loss and hypopigmentation. It also highlights the challenges in diagnosing and clinically managing syphilis in a resource-limited setting.

Malignant syphilis requiring differentiation from Kaposi's sarcoma.

Malignant syphilis (MS) is a rare variant of secondary syphilis. Also known as rupioid syphilis, MS is characterized by the presence of multiple papules, papulopustules, black lamellate crust that may resemble an oyster shell, or nodules with ulceration lacking central clearing. MS is often associated with immunodeficiency and frequently co-occurs with HIV infection. We here report a case of MS in a patient with HIV infection. HIV infection can cause atypical clinical symptoms of syphilis. In this case, unlike previous cases, cutaneous lesions of MS were limited to the face, making the diagnosis challenging based on clinical findings alone. However, his laboratory findings, appearance of the Jarisch-Herxheimer reaction, and a dramatic response to antibiotic therapy are characteristic of MS, making the diagnosis even more certain. Our case suggests the importance of physicians considering the possibility of MS when observing black-crusted lesions.

All Eyes and Ears: A Case of Neurosyphilis Presenting With Simultaneous Ocular and Otic Involvement.

This report details a case of neurosyphilis manifesting as concurrent ocular and otosyphilis, an uncommon presentation of the disease. Here, we describe the diagnosis and treatment of a 27-year-old immunocompetent Caucasian male who presented with uveitis and tinnitus. Physical exam was consistent with uveitis and audiometric testing revealed bilateral sensorineural hearing loss. Serum rapid plasma reagin (RPR) was reactive at 1:512 with a follow-up cerebrospinal fluid (CSF) venereal disease research laboratory (VDRL) test likewise reactive at 1:2, confirming neurosyphilis. The patient was treated with intravenous penicillin G with improvement of symptoms and with subsequent improvement of serum and CSF RPR. However, he ultimately represented with recurrent symptoms and fluctuating serum RPR levels, necessitating repeat treatment and ongoing clinical monitoring. Neurosyphilis can occur at any point during the course of a syphilis infection and may present with a variety of nonspecific findings. This case documents a particularly uncommon instance of simultaneous ocular and otosyphilis, a presentation of neurosyphilis that has only been described a handful of times.

Secondary Syphilis Presents as Palmoplantar Hyperpigmented Maculopapules: A Case Report.

Syphilis is a worldwide chronic systemic sexually transmitted infection caused by the spirochete bacterium Treponema pallidum. Here, we report a 28-year-old homosexual male who presented to the dermatology clinic with a six-month history of asymptomatic persistent skin lesions. A review of systems revealed unintentional weight loss of about 40 kg within one year. Skin examination revealed multiple scaly and non-scaly hyperpigmented macules and patches on the palms and soles. Hair, nail, and mucus membrane examinations were normal. There was no lymphadenopathy. A skin biopsy revealed psoriasiform acanthosis, lichenoid infiltrates with moderately dense mononuclear lymphohistiocytic cells, few plasma cells, and eosinophils. Laboratory investigations revealed positive rapid plasma reagin (RPR) with a titer of 1:128. Treponema pallidum hemagglutination test (TPHA) was positive. The HIV test by western blot was positive. Based on the above clinicopathological and laboratory findings, a diagnosis of secondary syphilis was made in this patient, who also tested positive for HIV. He was given a single dose of penicillin G benzathine (2.4 units) intramuscularly. He was also started on Dolutegravir 50 mg tablet once daily and Tenofovir alafenamide fumarate + Emtricitabine tablet once daily. Three months after penicillin G benzathine treatment, the RPR test turned negative, and the skin lesions disappeared.

Clinicopathologic assessment of secondary syphilis avoids misdiagnosis: results of comprehensive evaluation of 114 cases.

Introduction: Secondary syphilis is well-known for its protean cutaneous manifestations and therefore very easy to be misdiagnosed. Aim: The current study was to observe the frequency of histopathological features characterizing secondary syphilis, and summarize the diseases most likely to be misdiagnosed. Material and methods: In this study a total of 129 pathological specimens from 114 patients with biopsy-proven secondary syphilis were retrospectively analysed and categorized according to clinicopathologic characteristics. The frequency of histopathological features characterizing secondary syphilis were analysed by comparison with clinical features. Results: We found that in a single sample there is at least one feature or at most 13 features exist concurrently, and most demonstrated between 5 and 9 diagnostic features. Plasma cells (97.6% overall vs. 94.0% ≤ 6 features), endothelial swelling (86.8% vs. 74.0%), epidermis hyperplasia (73.6% vs. 62.0%) especially irregular acanthosis, lymphocytes infiltration (71.3% vs. 52.0%) and interstitial patterns (69% vs. 72.0%) were the most common findings in all cases as well as in cases with ≤ 6 features. Granulomatous inflammation is an uncommon histopathologic pattern in secondary syphilis (12.4%). The rash morphologies of our biopsies mainly manifesting as macules and maculopapules were more likely to have 6 or fewer features, which were not only easily misdiagnosed for pityriasis rosea, tinea and erythema multiforme, but also mostly taken from the trunk and genitalia. Atypical morphologies can be combined with plasma cell infiltration and T. pallidum immunohistochemical stain to confirm the diagnosis. Conclusions: In this study plasma cells from superficial and deep perivascular distribution to nodular infiltration were a crucial clue for diagnosis of secondary syphilis.

Moth eaten alopecia as the only manifestation of syphilis: a case from Nepal.

This paper presents a case of Moth-Eaten Alopecia as the only clinical manifestation of secondary syphilis in a 28-year-old man from Nepal. The patient exhibited progressive hair loss in the occipitoparietal region without associated pain or itching. With a positive Rapid Plasma Reagin (RPR) test (1:256), the patient received a three-week course of Benzathine Penicillin G, resulting in complete hair regrowth within four months. This case underscores the significance of recognizing moth eaten alopecia as a potential dermatological sign of secondary syphilis, especially when it appears as the sole clinical symptom.

Secondary syphilis presenting with non-arteritic anterior ischemic optic neuropathy (NAION).

Syphilis is a sexually transmitted disease caused by the spirochete bacterium Treponema pallidum. Syphilis is a significant public health issue, notably in (HIV) positive patients. Due to the absence of pathognomonic signs in secondary syphilis and its ability to present and mimic a wide variety of clinical findings, it gained the name "the Great imitator '(mimicker).' Herein, we describe a case of a 51-year-old man who presented with acute painless loss of vision of the right eye preceded by a few erythematous plaques with thick scales over bilateral legs and multiple discrete and confluent scaly papules over the palms and soles. During the hospital stay, a diagnosis of non-arteritic anterior ischemic optic neuropathy (NAION) as a manifestation of neurosyphilis is made. To the best of our knowledge, this is the first reported case of NAION as the presenting symptom of neurosyphilis in secondary syphilis in an immunocompetent patient.

A Case of Oropharyngeal Syphilis.

We present a case of a 50-year-old male who complained of a sore throat persisting for 2 months. Upon physical examination, multiple mucous patches were observed in the oropharynx region, but no skin lesions were found. Fiberoptic laryngoscopy confirmed these findings. The Treponema pallidum particle agglutination test and toluidine red unheated serum test (TRUST) were positive with a titer of TRUST 1:64. The patient admitted to engaging in extramarital sexual activities with several females but no males. Based on the clinical manifestations and laboratory test results, a diagnosis of secondary syphilis of the oropharynx was established. He was treated with 2.4 million units of benzathine penicillin G by intramuscular injection once a week for 3 weeks. After 1 month, the lesions completely disappeared without any symptoms. The titer of TRUST reduced to 1:2 in 1-year follow-up. This report aims to enhance physicians' understanding and recognition of oropharyngeal syphilis, enabling timely diagnosis and effective management.

Syphilitic unorthodoxy: A case of Lues Maligna in a human immunodeficiency virus-negative 28-year-old Filipino male

@#Lues maligna, also known as malignant syphilis, is an uncommon variant of syphilis at the secondary stage – more commonly reported in immunocompromised patients or those with concomitant human immunodeficiency virus (HIV) infection. In this report, we present a case of a 28‑year‑old HIV‑negative male with a 9‑month history of multiple, well‑defined, irregularly‑shaped, erythematous papules, and small plaques evolving to ulcerated plaques and nodules with crusts, associated with pain, pruritus, and episodes of fever, arthralgia, and weight loss. Positive treponemal and nontreponemal tests, aided by histopathologic findings consistent with syphilis led to the diagnosis of lues maligna. Significant improvement of lesions was noted with 3 weekly doses of 2.4 million units of benzathine penicillin G. For patients presenting with painful and pruritic erythematous ulcerated plaques with crusts associated with systemic symptoms, and with a significant sexual history despite testing negative for HIV infection, a high index of suspicion for uncommon presentations of other sexually transmitted infections such as syphilis could aid in early diagnosis and subsequent treatment.