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Abstract: Tertiary syphilis may present a diagnostic challenge due to negative nontreponemal serologies in up to 30% of cases and frequent lack of identifiable spirochetes on histopathology or other direct detection tests. We report 2 cases of round bodies staining with Treponema pallidum immunohistochemistry by light microscopy in biopsies from cutaneous syphilitic gummata. In 1 case, the finding was validated 3 times by 2 independent laboratories; in the other case, T. pallidum was detected by polymerase chain reaction in the biopsy sample. Spirochete round bodies have previously been reported in the setting of electron microscopy and fluorography, but to the best of our knowledge, have not been reported by light microscopy in a routine skin biopsy. Although the clinical implications are unclear, this may represent a helpful new paradigm for the diagnosis of tertiary syphilis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The authors declare no conflicts of interest.

Condyloma lata, a cutaneous manifestation of secondary syphilis, usually appear as verrucous papules and plaques in the anogenital area. Involvement of the umbilicus is very uncommon. Thus, awareness of this presentation, along with appropriate history, physical exam, and laboratory testing may aid clinicians in prompt and accurate diagnosis. We describe a patient with an unusual presentation of condyloma lata on the umbilicus.

The number of cases of syphilis continues to rise in the UK, USA and elsewhere and may present to a variety of clinical specialties. We report a complex case of early acquired disseminated syphilis causing an ulceronodular rash (lues maligna), orchitis, osteitis and lung nodules in an immunocompetent man who has sex with men who presented to the genitourinary medicine clinic. Syphilis should be considered in the differential diagnoses of multiple clinical presentations and optimal management should involve multidisciplinary care., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Syphilis is a venereal disease caused by treponema pallidum, historically known as "great mimicker" because of its variable presentations. Secondary syphilis usually presents with maculopapular or papulosquamous rash. Rare manifestations include papulonodular, annular and lichenoid lesions. Nodules are usually found in benign tertiary syphilis. We present a case of a young boy who presented with five months' history of nodular skin lesions and hoarseness of voice. Venereal disease research laboratory (VDRL) was initially negative owing to prozone phenomenon. However, histopathology was confirmatory and he responded to benzathine penicillin. We present this case because of rare clinical presentation with persistent nodular lesions, unusual age group, and negative initial VDRL test.

Syphilis is an infection caused by Treponema pallidum, mainly transmitted by sexual contact. Since 2001, primary and secondary syphilis rates started to rise, with an epidemic resurgence. The authors describe an exuberant case of secondary syphilis, presenting with annular and lichen planus-like lesions, as well as one mucocutaneous lesion. Physicians must be aware of syphilis in daily practice, since the vast spectrum of its cutaneous manifestations is rising worldwide.

The typical finding in secondary syphilis stage is a generalized non-pruritic maculopapular eruption. We report a case of secondary syphilis in an HIV-infected patient presenting with pruritic crusted nodules showing numerous eosinophils on the histopathological examination.

Early malignant syphilis is a rare and severe variant of secondary syphilis. It is clinically characterized by lesions, which can suppurate and be accompanied by systemic symptoms such as high fever, asthenia, myalgia, and torpor state. We report a diabetic patient with characteristic features of the disease showing favorable evolution of the lesions after appropriate treatment.

Acquired syphilis can be divided into primary, secondary, latent, and tertiary stages. About 25% of patients with untreated primary syphilis will develop late signs that generally occur after three to five years, with involvement of several organs. The authors present an immunocompetent female who developed a tertiary stage syphilis presenting with long-standing nodular plaques., Competing Interests: None.

Syphilis is a sexually transmitted disease caused by Treponema pallidum and divided into three stages according to the duration of the disease: primary, secondary and tertiary. Secondary syphilis has diverse clinical presentations, such as papular-nodular lesions. This presentation is rare, with 15 cases reported in the literature over the past 20 years. We report a case of secondary syphilis with papular-nodular lesions in a healthy 63-year-old patient, who has presented treponema in immunohistochemical examination of the skin lesions.

Background: Secondary syphilis has a wide spectrum of clinical and histologic manifestations., Objective: We sought to determine the frequency of histopathological features characterizing secondary syphilis, and which are most common in specimens displaying few diagnostic findings., Methods: In a multicenter, retrospective analysis of biopsy-proven secondary syphilis, cases were subcategorized by the number of histologic characteristics present., Results: The 106 cases mostly had 5 to 7 of the features studied. Many features were scarcer in cases with 5 or fewer features, including endothelial swelling (87.7% overall vs 72.4% ≤5 features), plasma cells (69.8% vs 48.3%), and elongated rete ridges (75.5% vs 27.6%). Specimens with 5 or fewer features were more likely to be truncal (61.1% vs 34.4% overall), demonstrate rete ridge effacement (44.8% vs 19.8%), and have pityriasis rosea (33.3% vs 17.2%) or drug eruption (33.3% vs 10.9%) in the clinical differential. An interstitial inflammatory pattern was the most common characteristic of specimens with 5 or fewer features (75.9%)., Limitations: This was a retrospective review., Conclusion: The independent value of many histologic features of syphilis may be overestimated. Combinations of endothelial swelling, interstitial inflammation, irregular acanthosis, and elongated rete ridges should raise the possibility of syphilis, along with the presence of vacuolar interface dermatitis with a lymphocyte in nearly every vacuole and lymphocytes with visible cytoplasm., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

A previously healthy 24-year-old man presented with an erythematous, non-pruritic and painless papulonodular skin rash affecting the trunk, upper arms (excluding palms), neck, face, forehead and scalp. He had a penile ulcer for the past 2 weeks, almost healed at the time of observation. The patient tested positive for syphilis and HIV-1; he claimed being negative for HIV 6 months earlier. As the palms were not affected, we performed a skin biopsy for the differential diagnosis between secondary lues and acute HIV seroconversion reaction. Benzathine penicillin (2,400,000 units) was administrated and antiretroviral therapy started. Although the skin biopsy was compatible with secondary syphilis, there was no change in the skin rash 3 weeks after the first penicillin administration. Another 2 doses of penicillin were given but 4 weeks later the rash persisted. A second biopsy revealed a mucinous skin infiltration, compatible with nodular mucinosis., (2015 BMJ Publishing Group Ltd.)

Syphilis has extremely variable manifestations that produce an extremely broad differential diagnosis. Care must be taken to consider syphilis in dermatologic and other systemic disorders as is relevant.

Malignant lues is a rare form of secondary syphilis mostly associated with HIV infection. It is an uncommon presentation of syphilis even rarer in immunocompetent patients. We present the case of a 57-year-old homosexual man referred to our department due to a 4-month history of a disseminated, slightly painful, nodular-ulcerative cutaneous eruption associated with low-grade fever, malaise and aesthenia. Regarding the clinical features and serological and histopathological findings, the diagnosis of syphilis maligna was assumed. Serology for HIV was repeatedly negative. This case is interesting, not only because a very uncommon form of secondary syphilis was identified but also for being diagnosed in an immunocompetent patient. Lack of awareness of this type of presentation delays the diagnosis and treatment, leading to an increase in morbidity and spread of infection., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Syphilis is a well-known sexually transmitted infection infamous for its protean cutaneous manifestations. Over the last decade, the rate of infection in the USA has risen, particularly among human immunodeficiency virus (HIV)-infected individuals and certain ethnic groups. Although the primary chancre developing at the site of inoculation usually has typical and well-characterized features, cutaneous manifestations of secondary syphilis span a wide spectrum and mimic those of other dermatoses. This may be particularly evident in patients with HIV. Such deviations from the expected typical papulosquamous eruption may present a diagnostic challenge and delay diagnosis and therapy. Given the increasing incidence of syphilis among the immunosuppressed patient population, recognition of atypical cutaneous manifestations is critical for adequate management. We review a range of cutaneous manifestations of secondary syphilis and the skin diseases it may mimic., (© 2014 The International Society of Dermatology.)

History and Clinical Findings: A 49-year-old, otherwise healthy man presented at his dermatologist with tuberous skin changes that had be present for several weeks on head, arm and leg. These were asymptomatic, but disturbed him cosmetically. A skin biopsy was performed., Investigations: The skin biopsy showed a granulomatous inflammation with prominent plasma cells, consistent with granulomatous infiltrate. Serologic tests confirmed a Treponema pallidum-infection. In addition, the patient was tested positive for hepatitis C and HIV (CDC stage A1). The clinical neurological examination did not show any pathological findings, however, analysis of the cerebrospinal fluid revealed a mild pleocytosis, elevation of protein and the glucose quotient and a normal Treponema pallidum TPPA-antibody index. A mesaortitis was excluded., Therapy and Course: We diagnosed a tertiary syphilis (stage III). The patient refused prolonged inpatient treatment with penicillin G i.v., as recommended as first-line therapy in the national guidelines for asymptomatic neurosyphilis. Therefore, after a single oral administration of 100 mg prednisolone he received ceftriaxone intravenously for 14 days. The skin changes resolved. With regard to the HIV infection anti-retro-viral therapy was not yet indicated., Conclusions: In view of the increasing incidence of syphilis in Germany clinicians should consider this diagnosis when confronted with oligosymptomatic skin lesions., (© Georg Thieme Verlag KG Stuttgart · New York.)

A 62-year-old male presented with a 10-day history of a diffuse, erythematous papular rash sparing the palms and soles. Histopathologic examination of a skin lesion showed loose non-caseating granulomas in a lymphoplasmacytic background. Scattered spirochetes were identified by Treponema pallidum immunohistochemistry, in keeping with a diagnosis of secondary syphilis. Granulomatous inflammation in secondary syphilis is uncommon. A review of the literature reveals that the majority of prior reported cases of granulomatous secondary syphilis share similar characteristics to this case; namely, a papular or nodular clinical presentation, sparing of the palms and soles, and collections of epithelioid histiocytes with associated lymphocytes and variable numbers of plasma cells., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We report the case of a 21-year-old woman with symmetrically distributed, ulcerated nodules and plaques on the face, neck and arms. Initial differential diagnoses included pyoderma or sarcoidosis based on the clinical presentation and histopathology with non-caseating granulomas. After inefficient treatment with topical and systemic fusidic acid and steroids, we diagnosed nodular secondary syphilis owing to positive serology and immunohistochemical staining of Treponema pallidum in lesional skin. After treatment with benzathine penicillin, skin lesions improved and antibody titres declined significantly within 3 months. Nodular skin lesions in secondary syphilis are rare with 15 reported cases within the last 20 years. Furthermore, the granulomatous histology is often misleading. Our patient's case suggests that the physicians should be aware of syphilis as a possible differential diagnosis also in patients outside a high-risk population for sexually transmitted diseases and with an unusual clinical presentation.

There are limited reports on the ultrastructure of syphilis skin lesions. The aim of this study has been to perform an electron microscopic investigation of the morphology and the tissue distribution of treponemes in primary and secondary cutaneous lesions. Three cases of primary syphilitic chancre and one case of secondary syphilis were included. Prominent epidermal abnormalities in the primary chancre and a perivascular inflammatory infiltrate in the secondary lesion were found by light microscopy. Ultrastructurally, spirochetes were located mainly in the blood vessel walls and dermal tissue of the chancre lesions. In the secondary syphilis case, spirochetes were more abundant between epidermal keratinocytes. Most of them adjusted to the intercellular spaces. Occasionally, the electron microscopy images were highly suggestive of an intracellular location. Both the ultrastructural and immunohistochemical examination of the primary and secondary syphilis lesions showed a paradoxical distribution of the causative microorganisms compared to the light microscopic changes. In addition, the ultrastructural findings strongly suggest that Treponema pallidum subspecies pallidum invades tissues, not only through an intercellular, but also through a transcellular pathway.

A granulomatous tissue response may be observed in untreated, long-standing lesions of secondary syphilis. In addition to poorly defined granulomatous inflammation, leprosy-like sarcoidal and palisaded granulomatous inflammation has been documented in literature reports of lues. Herein, we report a 47-year-old man who presented with a 3-month history of a generalized non-pruritic macular and papular rash located on the trunk and extremities. Histopathologically, there was an interstitial arrangement of histiocytes with occasional multinucleated giant cells positioned among collagen bundles without associated necrosis, thereby closely mimicking interstitial granuloma annulare. A clue to the diagnosis was the presence of admixed plasma cells. To the best of our knowledge, this is the first reported case of secondary syphilis showing an interstitial granulomatous pattern mimicking interstitial granuloma annulare., (Copyright © 2011 John Wiley & Sons A/S.)

There has been a recent increase in the incidence of syphilis in Slovenia, similar to other countries. Secondary syphilis can manifest with various clinical and histopathological presentations. We report the case of a 52-year-old patient that presented with nonpruritic nodular lesions on the face, trunk, and insteps that clinically mimicked lymphoma or sarcoidosis. Histopathological findings showed granulomatous inflammation. The serology revealed positive non-treponemal and treponemal tests. Treatment with benzathine penicillin G was successful.

A 77 year old man complained of vision loss and presented psoriasiform skin manifestations. A bilateral panuveitis was observed and after extensive investigation including vitrectomy the patient was diagnosed with secondary syphilis with ocular involvement. Syphilis has shown an increasing incidence in Sweden especially within the group of men who have sex with men. This case report reminds us of the diversity of symptoms which syphilis may present and the importance of PCR to demonstrate Treponema pallidum.

A case of secondary syphilis acquired by nonsexual household contact in a prepubertal girl is presented.

Seventy-nine cases of syphilis were the material of this study. Unusual presentations of primary syphilis were found in 42.5% of cases; explanations are given for these findings. Other aspects of the unusual presentations of the disease were studied with special stress on the occurrence of itching in the course of secondary syphilis. The authors emphasize that pruritus as a presenting symptom in the presence of skin lesion suggestive of syphilis should not blind the physician to the possibility that Treponema pallidum may be the etiologic agent.