Follmann’s balanitis: An heterogeneous clinical manifestation of primary syphilis

Introduction

Sexually transmitted infection (STI) rates have experienced a remarkable increase in the last two decades in Western world. Some populations such as men who have sex with men (MSM) have been especially affected. Besides, several outbreaks have been described in MSM like hepatitis A virus, ¹ lymphogranuloma venereum (LGV) ² or Shigella p. ³ Major vulnerability to infections is multifactorial; higher average number of sexual partners, lesser use of barrier measures, use of illicit drugs, or pre-exposure prophylaxis (PrEP) are different factors that could contribute. ⁴ HIV infection is the only one that has decreased in the later years in Spain thanks to universal treatment and PrEP. ⁵

The syphilis rate in Spain has increased from 2.32/100.000 cases in 2003 to 17.1/100.000 in 2022. ⁶ The clinical course of this infection includes periods with symptoms and others without (latent periods) where the only way to diagnose is through serology. ⁷ The first symptomatic period is primary syphilis, and its main characteristic is the chancre, a solitary, painless and indurated ulcer typically located on the genitals, anus or oral mucosae. Secondary syphilis can manifest in many different ways. The most common is a cutaneous rash affecting palms and soles. In secondary syphilis, the central nervous system can be affected, including ocular and auditory nerves.

Atypical manifestations of syphilis as Follman’s balanitis (FB) are rare. Nevertheless, due to the increasing rates of syphilis cases in the last decade, these rare presentations are more frequently seen.

FB is an atypical entity present in primary syphilis. Instead of the classical chancre, an extensive, erythematous, erosive lesion on the glans penis characterizes FB. ⁸ In addition, exudation and small papular lesions within have been described, in addition to bilateral lymphadenopathy. ⁹

Despite being described for first time in 1948, ¹⁰ literature on this matter is scarce. Only 23 articles have been published, mainly case descriptions.

The proposal of this article is to describe FB cases diagnosed in an STI Unit in Barcelona over the last 20 years.

Methods

This is a retrospective, descriptive study of FB cases at Vall d’Hebron – Drassanes STI Unit, from January 2003 to February 2023. All clinical records were analysed and epidemiological, clinical and microbiological data were collected.

Definition of FB criteria was an erosive balanitis plus at least one of these criteria: (1) a positive dark field, (2) positive molecular test (NAATs) for Treponema pallidum, (3) a serological positive test (two treponemal positive test positive or a treponemical and reaginical positive test).

NAAT performed was an in-house developed technique. We used the reverse algorithm for serological diagnosis. The first test done was CLIA for anti-treponemal antibodies (Treponemal Enzyme Immunoassay. Siemens Healthcare Diagnostics, Germany). If positive, TPHA (T. pallidum particle hemagglutination test. Biokit, Spain) and RPR (Rapid Plasma Reagin. Biokit, Spain) were subsequently added.

Continuous variables were described as median and interquartile range (IQR) and categorical variables were described as percentages, unless otherwise specified. IBM SPSS statistics software for Windows (Version 21; IBM, Armonk, NY, USA) was used for statistical analyses. The study protocol was approved by the Ethics Committee of Vall d’Hebron University Hospital (PR(AG) 410/2021.

Results

Twenty cases were collected along the period studied. During this time, 3585 early syphilis cases were diagnosed. FB prevalence was 5.5/1000 infections.

All patients except one transgender women who had sex men, were cisgender MSM (2 (10.5%) of them also had sex with women). Median age was 33 years (IQR 30.5–41.75), 11 (55%) were born in Spain, 3 (15%) in Latin America and 3 (15%) in Europe. Ten persons (50%) had had at least one STI before, and 5 (25%) one previous episode of syphilis. HIV infection was present in 6 (30%). Median time living with HIV at the time of diagnosis was 3 years (IQR 1.75–4.5). There were no new HIV diagnoses at the moment of FB presentation. Viral and immune data were available in five persons. Median CD4 count was 790 cells/mcL (IQR 576–875). Three had an undetectable viral load and two had 1980 and 144 copies/mL respectively.

The most frequent lesion described was erosive balanitis (Figure 1), with different variants in its appearance (see Table 1). Fifteen percent (4) had also a chancre and 50% (10) lymphadenopathy.OPEN IN VIEWER

OPEN IN VIEWER

Table 1.

Clinical manifestations and microbiological results of the cases of Follmann Balanitis.

	Clinical Manifestations	Gender	Orientation	HIV	Previous syphilis	Drugs	Dark field	PCR TP	RPR	Other test
1	Balanitis	Mc	MSM	neg	Yes	NIA	ND	ND	1/4	NIA
2	Múltiple non-indurated erythematous lesions on the glans	Mc	MSM	pos	Yes	NIA	neg	pos	1/2	HSV neg
3	Balanoposthitis	Mc	MSM	pos	No	NIA	ND	ND	1/32	NIA Initially treated with valaciclovir, with no clinical improvement
4	Erosive balanitis	Mc	MSM	neg	No	NIA	ND	ND	1/16	NIA
5	Balanitis	Mc	MSM	neg	No	NIA	ND	ND	1/4	NIA
6	Inflammation with exudate and significant preputial oedema, balanitis and indurated erosion at the balanopreputial junction	Mc	MSM	neg	NIA	NIA	pos	pos	RPR neg, TPHA+	HSV neg
7	Significant balanoposthitis with whitish exudate	Mc	MSM	neg	NIA	Yes	pos	pos	1/64 con TPHA+++	HVS neg Culture: strep pyogenes
8	Erosive/erythematous lesions at gland and the balanopreputial junction	Mc	MSMW	neg	No	Yes	neg	neg	1/8	HSV Neg culture neg
9	Erosive balanitis of the glans and a lesion suggestive of chancre at the balanopreputial junction	Mc	MSM	neg	NIA	NIA	pos	pos	1/4	HSV neg
10	Balanoposthitis	Mc	MSM	neg	Yes	NIA	pos	ND	1/32	NIA
11	Erosive lesion progressing to irregular shiny erythematous perimeatal plaque with small satellite macula	Mc	MSM	pos	Yes	NIA	neg	pos	1/32	HSV neg Initially treated with mupirocin, with no clinical improvement
12	Perimeatal erosive balanitis	Mc	MSM	pos	No	Yes	pos	pos	1/8	NIA
13	Erosive balanitis in the glans, with geographical borders, and postitis.	Mc	MSMW	neg	No	No	ND	pos	1/8	HSV Culture neg
14	Erosive balanitis in the glans, two ulcers on the shaft of the penis and postitis	Wt	WSM	neg	No	No	pos	pos	1/32	HSV neg
15	Balanitis with erythematous lesions with small excoriation	Mc	MSM	neg	No	No	ND	pos	neg	HSV neg
16	Erosive erythematous and exudative lesions on the glans	Mc	MSM	neg	No	NIA	neg	ND	1/2	HSV neg
17	Erosive and erythematous perimeatal area, faint macular rash on trunk	Mc	MSM	pos	No	NIA	ND	ND	1/2	NIA
18	Geographic not indurated ulcers at glans	Mc	MSM	neg	No	NIA	pos	pos	1/4	HSV neg
19	Erosive balanoposthitis and an indurated lesion near the sulcus. Left inguinal lymphadenopathy.	Mc	MSM	neg	No	No	neg	pos	1/4	HSV neg
20	Single hypopigmetanda lesion with punctate lesions in the gland and the balanopreputial junction	Mc	MSM	pos	Yes	NIA	ND	pos	neg	HSV neg Initially treated with clotrimazole, with no clinical improvement

Mc: cisgender man, Wt: transgender woman MSM: men who have sex with men. MSMW: men who have sex with men and women. WSM: women who have sex with men. Pos: positive. Neg: negative. ND: not done, NIA: no information available.

In 12 persons, a dark field was conducted, being positive in seven (58.3%). Treponema pallidum NAAT was positive in 12 out of 13 (92%). Median RPR titre was 1/4 (IQR 1/2–1/16). Three had a negative RPR and one had RPR 1/64. All of them were treated with Benzathine penicillin G 2.4 MU IM single dose.

Discussion

Follmann’s balanitis is a rare primary syphilis manifestation. The incidence in literature has been described as about 0.3–0.5%; ⁸ in our study the incidence was 10 times lower.

Audry and Chartellier published the first case in 1921, describing an erosive balanitis. ⁸ Ten years later, Follmann suggested that this syndrome could be related to Treponema pallidum primary infection. ¹⁰ He described a case of an erosive balanitis, with lymphadenopathy and absence of chancre in which dark field from the lesion was positive. Lejman published first histological description in 1975. ¹¹ He demonstrated the presence of Treponema in the epidermis and basal membrane probably due to hematogenous dissemination.

Most publications about FB are case descriptions.^12–14 In total, fewer than 100 cases have been reported, observing an increase in the last two decades (11 publications). This increase could be explained because of the rising rates that STIs have experienced. In Europe, the syphilis rate has doubled in the last 10 years, thus atypical manifestations are also more common. ¹⁵

Among the literature, there are two case series of five and three patients respectively.^8,13 As in our study, clinical symptoms are heterogeneous. Chancre can be present together with erosive balanitis or appear later on. ⁹ Balanitis characteristics can also vary between erosive, scaly, erythematous or indurated.^8,9 The typical location is the penis glans and the number of lesions is variable with confluent borders. These lesions can produce oedema.

Diagnosis is based in primary syphilis techniques like dark field, and NAATs. In our study median RPR was 1/4 but 45% had an RPR 1/8 or higher. A possible hypothesis is that, if FB is actually explained through an hematogenous dissemination, the immune reaction could begin sooner and RPR titers could be higher than usual. Knowing all clinical manifestations of Follman balanitis is key, as it can be confounded with secondary syphilis patterns, though in the latter lesions are not usually erosive.

Recently, Vezzoni et al. ¹⁶ questioned the usefulness of dermatoscopy for diagnosis. They described one case with “homogeneously distributed glomerular vessels and focused linear curved vessels on an erythematous background with hyperpigmented post-inflammatory area” which could be helpful for differential diagnosis. ¹⁶ Treatment does not differ from primary syphilis, with a correct evolution.

Conclusions

Our study is the largest series of cases published until today. We observed an incidence of 5.5/1000 infections. Clinical presentation is very variable, and chancre or lymphadenopathy can be present. RPR titres to be higher than in typical primary syphilis, though in occasions it can also be negative. FB has to be suspected in cases of an erosive balanitis, especially in key populations as MSM or persons with previous STIs, where syphilis is more frequent.