Dermatology Online Journal

Alopecia syphilitica-report of a patient with secondary syphilis presenting as moth-eaten alopecia and a review of its common mimickers
Ming Yang Bi AB¹, Philip R Cohen MD^2,3,4, Floyd W Robinson BS², James M Gray MD²
Dermatology Online Journal 15 (10): 6

1. Medical school, Baylor College of Medicine, Houston, Texas
2. University of Houston Health Center, University of Houston, Houston, Texas
3. Department of Dermatology, University of Texas-Houston Medical School, Houston, Texas
4. Department of Dermatology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas. mitehead@aol.com

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Abstract

Alopecia syphilitica is an uncommon manifestation of secondary syphilis, occurring in only 4 percent of these individuals. It is non-inflammatory and non-cicatricial hair loss that can present in a diffuse pattern, a moth-eaten pattern, or a combination of both. A 38-year-old, otherwise asymptomatic, homosexual man is described whose initial presentation of syphilis was patchy, moth-eaten, alopecia. In addition, differentiating features of alopecia syphilitica and other similar appearing non-cicatricial alopecias are reviewed. Conditions that mimic moth-eaten alopecia include other localized and non-cicatricial alopecias, such as alopecia areata, alopecia neoplastica, tinea capitis, and trichotillomania. The distinguishing clinical and laboratory features of alopecia syphilitica include other mucocutaneous changes associated with secondary syphilis, when present, and a positive serology for syphilis. The treatment of choice is a single intramuscular injection 2.4 million units of benzathine penicillin G for patients without immunocompromise; however, our patient was treated with three weekly doses because of concern about possible HIV positivity. The hair loss usually resolves within 3 months of treatment.

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Introduction

Alopecia syphilitica is an uncommon manifestation of secondary syphilis. It is non-inflammatory and non-cicatricial hair loss that can present in a diffuse pattern, a moth-eaten pattern, or a combination of both [1]. The scalp is the most commonly affected area. However, eyebrows, eyelashes, axilla, pubis, chest, and legs can also be affected [1-8]. Alopecia syphilitica often accompanies other mucocutaneous symptoms of secondary syphilis, but it can be the only presenting symptom. Individuals in whom diffuse alopecia syphilitica was the only initial presentation of secondary syphilis have been described [1]; however, there is a paucity of recent reports in which moth-eaten alopecia syphilitica was the only initial presentation. A 38-year-old homosexual man in whom moth-eaten alopecia was the only presenting manifestation of secondary syphilis is reported and differentiating features of similar appearing non-cicatricial alopecias are reviewed.

Case report

A 38-year-old, otherwise healthy, homosexual man presented with hair loss since March 2009. He reported progressive hair loss in 1 cm patches on his posterior scalp. His only medication was Astelin (azelastine HCl) nasal spray, which he started using a few weeks prior to presentation for seasonal allergies. The patient reported a stable domestic partner. However, he did not deny promiscuity outside of this relationship.

Figure 1

Examination of the posterior scalp showed moth-eaten alopecia in 1 cm patches (Fig. 1). These areas of alopecia were free from other cutaneous lesions. No hair loss was noted in his axilla, pubis, eyebrows, and eyelashes. Genital exam was normal and there was no lymphadenopathy or other mucocutaneous lesions.

Complete blood count and platelets, basic serum chemistries, liver function tests, thyroid function tests, and anti-nuclear antibodies were within normal limits or absent; his RPR was reactive with a titer of 1:256. Testing to determine the presence or absence of human immunodeficiency virus (HIV) was recommended. However, the patient refused further evaluation.

The patient was treated with three, weekly intramuscular injections of 2.4 million units of benzathine penicillin G. Upon completion of treatment, the patient reported no further progression of his alopecia.

Discussion

History

In 1940 McCarthy described two types of syphilis-associated alopecia. "Symptomatic syphilitic alopecia" can present as diffuse or moth-eaten alopecia, accompanied by other lesions of secondary syphilis on the scalp or elsewhere [1]. "Essential syphilitic alopecia" can present as diffuse alopecia, moth-eaten alopecia, or a combination of the two; the patient is otherwise free from any other cutaneous manifestations of secondary syphilis [1].

Epidemiology

The prevalence of reported alopecia syphilitica in secondary syphilis ranges from 4 percent to 12.5 percent [2, 9, 10, 11], with a predominance in homosexual men [10]. The largest study that examined the prevalence of alopecia syphilitica in secondary syphilis is a retrospective review of 854 patients with secondary syphilis between 1965-1984 at Middlesex Hospital in London. These patients included 72 (8.7%) heterosexual men, 695 (84.3%) homosexual men, and 57 (6.9%) women. From those with secondary syphilis, about 4 percent had developed alopecia syphilitica. Of those with alopecia syphilitica, 5 (15.6%) were heterosexual men, 24 (75.0%) were homosexual men, and 3 (9.4%) were women. The HIV-status of these patients was not specified [10]. In another study of 89 untreated patients with secondary syphilis at the University Teaching Hospital in Lusaka, Zambia, between February and December 1984, 10 (11.2%) patients were noted to have alopecia on the scalp. Again, the HIV status of these patients was not specified [2].

Studies have shown that HIV co-infection is common in patients with syphilis. Rates of HIV co-infection have been reported as high as 60 percent in Los Angeles and San Francisco, 51 percent in Chicago, and 34 percent in Houston [12]. These data raise the question as to whether there is a difference in the prevalence of alopecia syphilitica between those who are HIV positive and those who are HIV negative.

In a study of 24 HIV positive patients with syphilis treated at the Infectious Dermatology Outpatient Clinic of the Evandro Chagas Clinical Research Institute from 1997-2003 in Rio De Janeiro, Brazil, 3 (12.5%) patients presented with patchy alopecia [9]. Whether the percentages of alopecia syphilitica differ between HIV negative and HIV positive patients could not be concluded based on this study secondary to the small number of patients.

A predominance of men, especially homosexual men, presenting with alopecia syphilitica has been noted in the above reviews as well as reported cases [1-10]. This observation is not surprising given that more than 60 percent of new cases of syphilis occur in men who have sex with men [12].

Clinical presentation

Alopecia syphilitica is non-inflammatory and non-cicatricial hair loss associated with secondary syphilis. It can present either by itself without other mucosal or cutaneous lesions of secondary syphilis as "essential syphilitic alopecia," or with other symptoms of secondary syphilis, as "symptomatic syphilitic alopecia" [1]. Alopecia syphilitica is not seen in primary syphilis unless it is associated with a chancre of the scalp [11].

Alopecia in secondary syphilis can present as localized patches called moth-eaten alopecia, as diffuse alopecia, or as a combination of both [1]. Of these, moth-eaten alopecia is most common and most characteristic of alopecia syphilitica [11, 13].

The diffuse pattern of syphilis-associated alopecia is seldom reported in the current literature. Uncommonly, diffuse hair loss on the scalp and on other areas of the body has been observed as the only presenting symptoms of secondary syphilis [1]. Similarly, moth-eaten alopecia as the only presenting symptom of secondary syphilis, as demonstrated in our patient, has not recently been described.

Alopecia syphilitica can involve any area with hair, but most commonly, it involves the scalp [1-7]. Patients with alopecia syphilitica have also been reported in whom hair loss occurred on the eyebrows [4, 5, 6, 7], eyelashes [4, 5], chest [6], legs [6, 7], axilla [1], and pubis [1, 3].

Pathology

Distinguishing histopathologic features of alopecia syphilitica have not yet been established because of the lack of agreement amongst previous studies based on a limited number of biopsies. However, characteristics that are more commonly present or absent in alopecia syphilitica can be used as a guideline until larger studies are done.

In a histopathological study of 12 patients with moth-eaten alopecia in South Africa, Jordaan and Louw described the characteristic features of alopecia syphilitica: "follicular plugging, a sparse, perivascular and perifollicular lymphocytic infiltrate, and telogenization and follicle-oriented melanin clumping" [13].

Lee and Hsu also conducted a histopathological study of 9 patients with alopecia syphilitica in Taiwan. Four patients had moth-eaten alopecia and the remaining 5 had a diffuse but slightly moth-eaten pattern. Their key findings include a normal dermoepidermal junction, decreased number of hair follicles, catagenization, telogenization, and the presence of sparse lymphocytes around hair bulbs and fibrous tracts. Plasma cells were noted in 4 of the 9 specimens. In 2 of the 4 specimens with plasma cells, only 1 or 2 plasma cells were noted; in the remaining 2 biopsies, slightly more numerous plasma cells were seen. With the exception of follicular changes, these histopathologic findings resemble macular/maculopapular syphilides outside the scalp. With follicular changes, alopecia syphilitica bore a close resemblance to alopecia areata [14].

According to Lee and Hsu, alopecia areata can be differentiated from alopecia syphilitica by the presence of peribulbal eosinophils. A peribulbal eosinophilic infiltrate was not noted in all 9 specimens of alopecia syphilitica but was noted in 9 (69%) of 13 specimens of alopecia areata. These results were statistically significant by Fisher's exact probability test (p=0.00144) [14].

Jordaan and Louw, however, found that 3 out of 12 biopsies of alopecia syphilitica contained eosinophils and concluded that a larger study is needed to determine the utility of eosinophils in distinguishing alopecia syphilitica from alopecia areata. Instead, they concluded that the sparse lymphocytic infiltrate and the absence of small or abnormal anagen hair follicles in alopecia syphilitica most reliably distinguish it from alopecia areata [13].

Differential Diagnosis

Diffuse alopecia syphilitica may mimic telogen effluvium or possibly androgenic alopecia, but common mimickers of moth-eaten alopecia syphilitica include other localized, non-cicatricial alopecias. These include alopecia areata, alopecia neoplastica, tinea capitis, and trichotillomania (Table 1) [13-20].

Alopecia Areata. Alopecia areata presents as a sudden, well-demarcated, localized hair loss that is most common on the scalp. It can affect any area with hair, such as the beard or eyebrows. The etiology and pathogenesis of alopecia areata are unclear. Its association with human leukocyte antigen as well as an increased frequency of auto-antibodies and other autoimmune diseases point to an organ-specific autoimmune disorder [15].

Characteristic "exclamation point hairs" that taper proximally and thicken distally can be found in or at the periphery of the patch of alopecia. During regrowth, hairs may initially lack pigment, resulting in blonde or white hairs. Nails may also be involved; associated nail plate changes can include pitting, trachyonychia, Beau lines, or onychorrhexis [15].

A biopsy would show dense, CD₄+ and CD₈+ T lymphocyte infiltrates in the peribulbar region, described as a "swarm of bees." In addition, there can be an increased number of catagen and telogen follicles and eosinophilic infiltration in the stellae. Along the basement membrane of the inferior part of hair follicles, immunofluorescence studies have detected deposits of C3, IgG, and IgM [15].

Because alopecia areata can be associated with other autoimmune diseases such as thyroid disorders and pernicious anemia, laboratory evaluation (including thyroid function tests, thyroid antibodies, and a complete blood count and platelets) may be considered. Corticosteriods (intralesional, topical, or systemic) have been used to halt disease activity [15].

Alopecia Neoplastica. Alopecia neoplastica is defined as hair loss due metastasis of a visceral malignancy to the scalp [16, 17]. In a review of 25 patients with alopecia neoplastica, 22 patients presented with alopecia months or years after the primary tumor was diagnosed. Of the remaining 3 patients, alopecia was the initial presentation of cancer in 2 patients and alopecia and cancer were concurrent diagnoses in 1 patient [16].

When alopecia is the first presenting sign of malignancy, a biopsy would give a definitive diagnosis. Histologic examination would show infiltration of tumor cells from the primary malignancy. Treatment involves managing the primary neoplasm, although subsequent diffuse alopecia is a common transient side effect of antineoplastic therapy [16].

Tinea Capitis. Tinea capitis is an infection of hair follicles by dermatophytes and can present as inflammatory or non-inflammatory alopecia. In North America, Trichophyton tonsurans and Microsporum canis are responsible for the majority of the cases [18]. This infection is commonly seen in African American children under the age of 12 [19].

Infections with dermatophytes can be either endothrix or ectothrix. Endothrix invasions are typically caused by T. tonsurans in North America. This infection is characterized by fungal invasion of the hair shaft, while the cuticle of the hair remains intact. Hairs infected this way break at the scalp and do not fluoresce when examined with an ultraviolet Wood light [19].

Ectothrix invasion are typically caused by M. canis in North America. This infection is characterized by invasion of the hair cuticle, resulting in brittle hair and breakage distal to the scalp. This type of invasion fluoresces green under Wood light [19].

When lesions become secondarily infected, a kerion may develop. A kerion manifests as an erythematous plaque with pustules, which may result in scaring [19].

Diagnosis of tinea capitis can be made by light microscope examination of scalp scrapings after applying 10 percent potassium hydroxide and fungal culture on Sabouraud's medium [19]. Systemic antifungal treatment is needed to penetrate hair follicles and should be continued for 6-8 weeks [18].

Trichotillomania. Trichotillomania, an impulse control disorder, is characterized by chronic, compulsive pulling of one's own hair, usually in response to stress or as a manifestation of psychiatric disorders. Hair-pulling may take place during dedicated times (when the patient devotes all his or her attention to hair-pulling) or during sedentary activities, such as watching television or reclining in bed [20].

Clinically, trichotillomania presents as irregular, localized patches of alopecia predominantly in the vertex, occipital, and parietal regions. On close exam, patches of hair loss show broken hairs of varying lengths [20].

Histologically, torn away hair follicles with exudates or hemorrhage are diagnostic, but this is seen only in the minority of patients. Trichomalacia, or complete distortion of a fully developed terminal hair in the bulb, is also diagnostic for the disorder and is also noted in a small percentage of patients. Inflammation of the hair bulb and atrophic anagen hairs are both absent [20].

A diagnosis can be made when patients admit to hair-pulling. A scalp biopsy is indicated when patients are unable to communicate. Therapy involves parental support and education, behavioral therapy, pharmacotherapy, and/or psychiatric evaluation, depending on the age of the patient, the severity of the problem, and the presence of psychiatric co-morbidities [20].

Pathogenesis

The pathogenesis of syphilis and alopecia syphilitica has not been completely elucidated. Because of limited information from human studies, the postulated pathogenesis of syphilis is largely derived from animal models [21].

It is postulated that Treponema pallidum penetrates through small breaks in the skin [21]. Singh and Romanowski reviewed the postulated mechanisms of pathogenesis and summarized earlier relevant studies. One study involving intracutaneous inoculation of the spirochete in rabbits showed that the size of the inoculum was directly related to the probability that dark-field positive lesions were produced. Although on average, a chancre appears 3 weeks after the initial inoculation, a study showed that with a larger inoculum, a shorter incubation period was observed, such that with an inoculum of 107 organisms, a chancre appeared in 5-7 days. In another study with human volunteers inoculated with these organisms, similar results were obtained. Animal studies also showed that upon inoculation, organisms appeared in lymph nodes within minutes and disseminated throughout the body within hours [21].

T. pallidum has been shown to attach to mammalian cells in vitro. Although the exact mechanism by which the spirochete enters mammalian cells is unknown, it has been postulated that the organism enters via binding to specific ligands. T. pallidum has been shown to penetrate endothelial cell monolayers and intact membranes; this invasion seems to be a critical virulence factor [21].

In primary lesions, T. pallidum were invariably detected with silver stain; in secondary lesions, spirochetes were detected in 70 percent of the patients [21]. Hence, since spirochetes are not detected in all secondary lesions, it remains to be determined if spirochetes are directly responsible for alopecia syphilitica.

The pathogenesis of alopecia syphilitica has not been elucidated due to failure to consistently demonstrate the presence of spirochetes in hair follicles. In 1991, Lee and Hsu speculated that the peribulbal inflammation seen in 9 scalp biopsies suggests that alopecia syphilitica is caused by locally present spirochetes, although they were unable to detect any organism with the modified Steiner stain. They did note, however, that other than the follicular changes, the histopathological findings were similar to those of macular/macularpapular sphilides outside the scalp [14]. This finding suggests that the same pathologic process that occurs in mucocutaneous syphilides could also be responsible for alopecia syphilitica.

In 2006, Nam-Cha et al. detected T. pallidum in an immunohistochemical study of a biopsy of a 24-year-old, HIV positive Hispanic man with alopecia syphilitica. The spirochete was detected in the peribulbar region and penetrated into the follicle matrix. The authors utilized the avidin-biotin-peroxidase complex technique that involved a heat-induced epitope retrieval buffer and a primary antibody against T. pallidum. This was the first time that organisms were detected in hair follicles, supporting the speculation that T. pallidum may be responsible for alopecia syphilitica [22].

Treatment

The preparation, dosage, and duration of treatment vary, depending on the stage of syphilis, HIV status of the patient, and presence of neurosyphilis [23, 24, 25, 26]. The remainder of this discussion focuses on treatment for alopecia syphilitica, which is the same as for secondary syphilis.

There is a paucity of randomized, controlled trials comparing different drugs or preparations in the treatment of syphilis. Consequently, current treatment recommendations are based on opinions of experts, findings in case series, and results from non-randomized trails [24]. Guidelines from different regions vary and depend on regional traditions, preferences for oral versus parenteral medications, and availability of resources [24].

According to the Center for Disease Control and Prevention 2006 guidelines, a single intramuscular injection of 2.4 million units of benzathine penicillin G is the treatment of choice for secondary syphilis in patients without immunocompromise [23]. Alopecia usually resolves within 3 months of treatment [6]. However, serologic failure rate up to 25 percent has been reported [25].

For those allergic to penicillin, oral doxycycline 100 mg twice daily for 2 weeks or tetracycline 500 mg 4 times daily for 2 weeks or azithromycin 500 mg daily for 1 week can be given [23, 26]. These drugs, however, poorly penetrate the blood-brain barrier; therefore, they cannot reliably treat or prevent neurosyphilis, even in non-HIV infected patients [25]. Furthermore, studies have reported macrolide-resistant T. pallidum in the United States and resistance has been reported as high as 88 percent in Ireland [23, 24]. The Center for Disease Control and Prevention advises caution when using these alternative drugs because data is limited to support their use in treating early syphilis [23].

For patients who are HIV positive and who have syphilis without neurologic symptoms, the Center for Disease Control and Prevention recommends a single dose (or additional treatments such as 3 weekly doses) of 2.4 million units of benzathine penicillin G [23]. Because patients have progressed to neurosyphilis after a single dose [25], the more conservative approach of 3 weekly doses may be needed for those who are HIV positive or for those whose HIV status is unknown [23, 26]. It is unclear, however, whether repeated doses or larger doses of benzathine penicillin would prevent neurosyphilis [25].

For patients with neurosyphilis, the Center for Disease Control and Prevention recommends aqueous crystalline penicillin G 3-4 million units given intravenously every 4 hours, or as continuous infusion totaling 18-24 million units per day, for 10-14 days [23].

Treatment guidelines for syphilis change throughout the years; therefore, referring to the latest guidelines is recommended prior to treatment.

Conclusion

Alopecia syphilitica is an uncommon manifestation of secondary syphilis. It is non-inflammatory and non-citracrical hair loss that can present in a diffuse pattern, a moth-eaten pattern, or a combination of both [1]. It most commonly affects the scalp. However, any area with hair can be affected [1-7]. Patients often present with other mucocutaneous symptoms of secondary syphilis.

Clinical conditions that mimic diffuse alopecia syphilitica include telogen effluvium and androgenic alopecia; those that mimic moth-eaten alopecia syphilitica include alopecia areata, alopecia neoplastica, tinea capitis, and trichotillomania. When patients present with a non-inflammatory and non-cicatricial alopecia with a moth-eaten pattern, syphilis should be in the differential diagnosis. A complete skin examination for other mucocutaneous lesions of secondary syphilis and serological tests evaluating for syphilis should be done to confirm the diagnosis.

Histologically, plasma cells may be present in the perifollicular infiltrate of alopecia syphilitica lesions. The other pathologic changes of alopecia syphilitica can closely resemble those observed in alopecia areata [14]. However, features that can distinguish alopecia syphilitica from alopecia areata include absence of eosinophils [14], sparse lymphocytic infiltrate [13], and absence of small or abnormal anagen hair follicles [13].

The treatment of choice is a single intramuscular injection of 2.4 million units of benzathine penicillin G [23]. However, 3 weekly doses should be given to those who are HIV positive or to those whose HIV status is unknown [23, 26]. Alopecia is expected to resolve within 3 months of treatment [6].

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