Disseminated Lyme Disease Presenting With Nonsexual Acute Genital Ulcers | Critical Care Medicine | JAMA Dermatology | JAMA Network
[Skip to Navigation]
Sign In
Case Report/Case Series
November 2014

Disseminated Lyme Disease Presenting With Nonsexual Acute Genital Ulcers

Author Affiliations
  • 1Department of Dermatology, University of Connecticut School of Medicine, Farmington
  • 2Department of Internal Medicine, University of Connecticut School of Medicine, Farmington
  • 3Generations Health Center, Willimantic, Connecticut
JAMA Dermatol. 2014;150(11):1202-1204. doi:10.1001/jamadermatol.2014.1072

Importance  Nonsexual acute genital ulceration (NAGU) is a rare vulvar skin condition typically affecting girls and young women, characterized by acute onset of singular or multiple painful vaginal ulcers. The etiology of this ulcerative dermatosis has not been identified, although it has been associated with systemic infections. To our knowledge, this is the first report of an association with Lyme disease.

Observations  A case of a woman with early disseminated Lyme disease presenting with NAGU is reported. A thorough workup ruled out other causes of genital ulceration, and the ulcers completely resolved after treatment with topical steroids and oral doxycycline.

Conclusions and Relevance  Although the etiology of NAGU is unknown, the vulvar ulcers may result from an exuberant immune response to infection. Most patients with NAGU exhibit nonspecific symptoms such as myalgias and fever, suggesting an infectious agent, but the majority have no identifiable pathogen. In addition to previously reported associations with systemic infection, which are reviewed herein, Lyme disease should be considered in women presenting with acute-onset genital ulcers.

Report of a Case

A previously healthy woman in her 50s presented to the dermatology clinic with a 3-week history of rapidly expanding painful vaginal ulcers, neck and back pain, fever, malaise, and a tender “sunburn” on her shoulders. Skin evaluation 10 days prior at her primary care clinic revealed similar smaller genital ulcers and an annular erythematous patch on her abdomen with a “central raised mole.” Lyme titer testing had negative results. The patient denied sexual activity in more than 12 years. She had no history of sexually transmitted infection including genital herpes; no ocular symptoms including eye pain, redness, or visual changes; no oral ulcers or any previous history of genital ulcers. She took no long-term medications. The ulcers continued to progress despite treatment with oral ciprofloxacin (for a concomitant urinary tract infection), oral prednisone (6-day tapering protocol beginning at 24 mg/d), and topical neomycin ointment.

On examination, she had multiple well-defined, punched-out, painful, 2- to 12-mm diameter purulent ulcers on her labia minora (Figure 1). Symmetrically distributed across her shoulders and arms was a large, poorly demarcated tender erythematous patch consistent with a sunburn. Her oropharynx was normal. Multiple biopsies of her vaginal ulcers were performed, and she was prescribed lidocaine hydrochloride gel, 5%, and triamcinolone gel, 0.1%, twice daily.

Figure 1.  Genital Ulcers
Genital Ulcers

The patient presented with these multiple painful ulcers distributed bilaterally on the vulvar labial mucosa.

Biopsies of vaginal ulcerations showed an epidermal ulcer with adjacent polymorphous inflammatory infiltrate. There were no viral cytopathic features or changes of vasculitis. Immunohistochemical and special stains for fungal elements, bacteria, parasites, spirochetes, and herpes simplex virus (HSV) had negative results. Direct immunofluorescence testing had negative results. Tissue cultures were negative for bacteria and viruses. Additional laboratory tests demonstrated a positive result for HSV-2 IgG, elevated serum C-reactive protein level (186 mg/L; reference value, <5 mg/L [to convert to nanomoles per liter, multiply by 9.524]), and weakly positive antinuclear antibody test result (1:40). Normal laboratory values were obtained for rapid plasma reagin, tests for Chlamydia and Neisseria gonorrhoeae, complete blood cell count, and tests for antibodies to Borrelia burgdorferi, Babesia, Ehrlichia, human immunodeficiency virus (HIV) types 1 and 2, HSV-1, and double-stranded DNA. Serologic testing for Epstein-Barr virus was not performed.

Two weeks later, the patient presented with worsening fatigue, myalgias, neck and back pain, and new-onset headaches. Her fevers had waned, and the treated vaginal ulcers had improved slightly. Skin examination now demonstrated multiple 5- to 20-cm diameter pink, annular patches on her back and shoulders (Figure 2).

Figure 2.  Erythema Migrans
Erythema Migrans

Multiple erythema migrans lesions are distributed on the trunk and arms, representing disseminated (stage 2) Lyme disease.

The patient was prescribed doxycycline 100 mg twice daily for suspected secondary Lyme disease, and within 48 hours, she noted resolution of all symptoms including fatigue, neck pain, and rash and rapid improvement of the vulvar ulcers. Repetition of the Lyme enzyme-linked immunosorbent assay and Western blot test now revealed positive results. A punch biopsy of the edge of a patch showed interstitial histiocytic dermatitis with focal interface changes. Additional laboratory testing at this time included a nutrition panel, which had unremarkable results. A pathergy test was performed and had negative results. Her vaginal ulcers completely resolved without scarring, and she had not experienced any recurrence of the ulcers at 12-month follow-up.


Nonsexual acute genital ulceration (NAGU), formerly referred to as Lipschütz ulcers, is characterized by acute onset of singular or multiple painful vaginal ulcers with no identifiable etiology and nonspecific pathologic analysis in women and girls with no prior history of oral or genital ulcers. Most women with NAGU exhibit nonspecific systemic symptoms, such as myalgias or fever. This suggests an infectious etiology, but in more than 75% of patients, no pathogen is identified.1 In other cases, NAGU has been associated with systemic infection due to Epstein-Barr virus,2Mycoplasma, aerobic bacteria, HIV, mumps, cytomegalovirus, influenza A, and Toxoplasma gondii.3 To our knowledge, this is the first reported case of NAGU associated with Lyme disease.

The differential diagnosis of vaginal ulcerations is long and includes sexually transmitted infections, inflammatory diseases (most notably Behçet disease and complex aphthosis), systemic illness, and drug reactions.1 Our patient took no medication and had no sexually transmitted infections. Although her HSV-2 IgG serologic test had positive results, she had no history of genital herpes, and lesional tissue demonstrated negative viral culture results, absence of viral cytopathic changes, and negative HSV-2 immunostaining. In the absence of any oral or ocular lesions, gastrointestinal disorder, autoimmune disorder, or pathergy, Behçet disease is unlikely. Complex aphthosis is a diagnosis of exclusion,4 sometimes associated with nutritional deficiencies, which were not identified in our patient. Unfortunately, Epstein-Barr virus serologic analyses were not performed.

The simultaneous onset of acute genital ulcers with Lyme disease, worsening with progression of Lyme disease, and dramatic improvement without recurrence on treatment of Lyme disease support the diagnosis of Lyme-associated NAGU. In retrospect, the patient’s “sunburn” was probably an ill-defined patch of erythema migrans, and it is possible that the “raised mole” found at her visit to a different clinic was a tick located in the center of her primary erythema migrans.

Although the etiology of NAGU is unknown, the vulvar ulcers may result from an exuberant immune response to infection.5 Immunologic phenomena are not foreign to Borrelia infection: lymphocytoma cutis is a well-recognized manifestation of tick bite, and reports of immunologic manifestations of Lyme disease include lichen sclerosus et atrophicus,6 Behçet disease,7,8 morphea, Parry-Romberg syndrome, cutaneous B-cell lymphoma, eosinophilic fasciitis, granuloma annulare, infantile papular acrodermatitis, and urticarial vasculitis.9


With the case presented herein, we can consider NAGU among the protean immunologic manifestations of Lyme disease. Lyme titer analysis should be considered for women presenting with genital ulcers of unclear etiology.

Back to top
Article Information

Corresponding Author: Justin J. Finch, MD, Department of Dermatology, University of Connecticut, 21 South Rd, Farmington, CT 06030 (finch@uchc.edu).

Accepted for Publication: April 27, 2014.

Published Online: August 27, 2014. doi:10.1001/jamadermatol.2014.1072.

Author Contributions: Dr Finch had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Finch, Wald.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Finch, Wald.

Critical revision of the manuscript for important intellectual content: Finch, Ferenczi, Khalid, Murphy.

Administrative, technical, or material support: Finch.

Study supervision: Finch, Murphy.

Conflict of Interest Disclosures: None reported.

Chanal  J, Carlotti  A, Laude  H, Wallet-Faber  N, Avril  MF, Dupin  N.  Lipschütz genital ulceration associated with mumps.  Dermatology. 2010;221(4):292-295.PubMedGoogle ScholarCrossref
Farhi  D, Wendling  J, Molinari  E,  et al.  Non-sexually related acute genital ulcers in 13 pubertal girls: a clinical and microbiological study.  Arch Dermatol. 2009;145(1):38-45.PubMedGoogle ScholarCrossref
Huppert  JS.  Lipschutz ulcers: evaluation and management of acute genital ulcers in women.  Dermatol Ther. 2010;23(5):533-540.PubMedGoogle ScholarCrossref
Letsinger  JA, McCarty  MA, Jorizzo  JL.  Complex aphthosis: a large case series with evaluation algorithm and therapeutic ladder from topicals to thalidomide.  J Am Acad Dermatol. 2005;52(3, pt 1):500-508.PubMedGoogle ScholarCrossref
Berlin  C.  The pathogenesis of the so-called ulcus vulvae acutum.  Acta Derm Venereol. 1965;45(3):221-222.PubMedGoogle Scholar
Fistarol  SK, Itin  PH.  Diagnosis and treatment of lichen sclerosus: an update.  Am J Clin Dermatol. 2013;14(1):27-47.PubMedGoogle ScholarCrossref
Galeone  M, Colucci  R, D'Erme  AM, Moretti  S, Lotti  T.  Potential infectious etiology of Behçet’s disease.  Patholog Res Int.2012;2012:595380.Google Scholar
di Meo  N, Quaranta  L, Crisman  G, Trevisan  G.  Adamantiades Behçet disease triggered by a tick bite and or Borrelia infection.  J Eur Acad Dermatol Venereol. 2009;23(10):1198-1199.PubMedGoogle ScholarCrossref
Bhate  C, Schwartz  RA.  Lyme disease: part I. advances and perspectives.  J Am Acad Dermatol. 2011;64(4):619-636.PubMedGoogle ScholarCrossref