Research

Case Report/Case Series

Disseminated Lyme Disease Presenting

With Nonsexual Acute Genital Ulcers
Justin J. Finch, MD; Jenna Wald, MD; Katalin Ferenczi, MD; Saima Khalid, MD, MPH; Michael Murphy, MD

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
Author Affiliations: Department of
ulcers completely resolved after treatment with topical steroids and oral doxycycline. Dermatology, University of
Connecticut School of Medicine,
CONCLUSIONS AND RELEVANCE Although the etiology of NAGU is unknown, the vulvar ulcers Farmington (Finch, Ferenczi,
Murphy); Department of Internal
may result from an exuberant immune response to infection. Most patients with NAGU
Medicine, University of Connecticut
exhibit nonspecific symptoms such as myalgias and fever, suggesting an infectious agent, but School of Medicine, Farmington
the majority have no identifiable pathogen. In addition to previously reported associations (Wald); Generations Health Center,
with systemic infection, which are reviewed herein, Lyme disease should be considered in Willimantic, Connecticut (Khalid).

women presenting with acute-onset genital ulcers. Corresponding Author: Justin J.

Finch, MD, Department of
Dermatology, University of
JAMA Dermatol. 2014;150(11):1202-1204. doi:10.1001/jamadermatol.2014.1072 Connecticut, 21 South Rd,
Published online August 27, 2014. Farmington, CT 06030
(finch@uchc.edu).

Figure 1. 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 expand-
ing painful vaginal ulcers, neck and back pain, fever, mal-
aise, and a tender “sunburn” on her shoulders. Skin evalua-
tion 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 sexu-
ally transmitted infection including genital herpes; no ocu-
lar 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 con-
tinued 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. The patient presented with these multiple painful ulcers distributed bilaterally
On examination, she had multiple well-defined, punched- on the vulvar labial mucosa.

out, painful, 2- to 12-mm diameter purulent ulcers on her la-

bia minora (Figure 1). Symmetrically distributed across her Biopsies of vaginal ulcerations showed an epidermal ulcer
shoulders and arms was a large, poorly demarcated tender ery- with adjacent polymorphous inflammatory infiltrate. There were
thematous patch consistent with a sunburn. Her oropharynx no viral cytopathic features or changes of vasculitis. Immuno-
was normal. Multiple biopsies of her vaginal ulcers were per- histochemical and special stains for fungal elements, bacteria,
formed, and she was prescribed lidocaine hydrochloride gel, parasites, spirochetes, and herpes simplex virus (HSV) had nega-
5%, and triamcinolone gel, 0.1%, twice daily. tive results. Direct immunofluorescence testing had negative re-

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 Disseminated Lyme Disease With Genital Ulcers Case Report/Case Series Research

sults. Tissue cultures were negative for bacteria and viruses. Ad-
Figure 2. Erythema Migrans
ditional laboratory tests demonstrated a positive result for HSV-2
IgG, elevated serum C-reactive protein level (186 mg/L; refer-
ence value, <5 mg/L [to convert to nanomoles per liter, multi-
ply by 9.524]), and weakly positive antinuclear antibody test re-
sult (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 vi-
rus (HIV) types 1 and 2, HSV-1, and double-stranded DNA. Se-
rologic testing for Epstein-Barr virus was not performed.
Two weeks later, the patient presented with worsening fa-
tigue, myalgias, neck and back pain, and new-onset head-
aches. 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).
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 Multiple erythema migrans lesions are distributed on the trunk and arms,
of the Lyme enzyme-linked immunosorbent assay and Western representing disseminated (stage 2) Lyme disease.
blot test now revealed positive results. A punch biopsy of the edge
of a patch showed interstitial histiocytic dermatitis with focal in- HSV-2 immunostaining. In the absence of any oral or ocular le-
terface changes. Additional laboratory testing at this time in- sions, gastrointestinal disorder, autoimmune disorder, or
cluded a nutrition panel, which had unremarkable results. A pathergy, Behçet disease is unlikely. Complex aphthosis is a di-
pathergy test was performed and had negative results. Her vagi- agnosis of exclusion,4 sometimes associated with nutritional de-
nal ulcers completely resolved without scarring, and she had not ficiencies, which were not identified in our patient. Unfortu-
experienced any recurrence of the ulcers at 12-month follow-up. nately, 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 dra-
matic improvement without recurrence on treatment of Lyme
Discussion disease support the diagnosis of Lyme-associated NAGU. In ret-
Nonsexual acute genital ulceration (NAGU), formerly re- rospect, the patient’s “sunburn” was probably an ill-defined
ferred to as Lipschütz ulcers, is characterized by acute onset patch of erythema migrans, and it is possible that the “raised
of singular or multiple painful vaginal ulcers with no identi- mole” found at her visit to a different clinic was a tick located
fiable etiology and nonspecific pathologic analysis in women in the center of her primary erythema migrans.
and girls with no prior history of oral or genital ulcers. Most Although the etiology of NAGU is unknown, the vulvar ul-
women with NAGU exhibit nonspecific systemic symptoms, cers may result from an exuberant immune response to
such as myalgias or fever. This suggests an infectious etiol- infection.5 Immunologic phenomena are not foreign to Borrelia
ogy, but in more than 75% of patients, no pathogen is infection: lymphocytoma cutis is a well-recognized manifesta-
identified.1 In other cases, NAGU has been associated with sys- tion of tick bite, and reports of immunologic manifestations of
temic infection due to Epstein-Barr virus,2 Mycoplasma, aero- Lyme disease include lichen sclerosus et atrophicus,6 Behçet
bic bacteria, HIV, mumps, cytomegalovirus, influenza A, and disease,7,8 morphea, Parry-Romberg syndrome, cutaneous B-cell
Toxoplasma gondii.3 To our knowledge, this is the first re- lymphoma, eosinophilic fasciitis, granuloma annulare, infan-
ported case of NAGU associated with Lyme disease. tile papular acrodermatitis, and urticarial vasculitis.9
The differential diagnosis of vaginal ulcerations is long and
includes sexually transmitted infections, inflammatory diseases
(most notably Behçet disease and complex aphthosis), systemic
Conclusions
illness, and drug reactions.1 Our patient took no medication and
had no sexually transmitted infections. Although her HSV-2 IgG With the case presented herein, we can consider NAGU among
serologic test had positive results, she had no history of geni- the protean immunologic manifestations of Lyme disease.
tal herpes, and lesional tissue demonstrated negative viral cul- Lyme titer analysis should be considered for women present-
ture results, absence of viral cytopathic changes, and negative ing with genital ulcers of unclear etiology.

ARTICLE INFORMATION Published Online: August 27, 2014. Author Contributions: Dr Finch had full access to
Accepted for Publication: April 27, 2014. doi:10.1001/jamadermatol.2014.1072. all of the data in the study and takes responsibility

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 Research Case Report/Case Series Disseminated Lyme Disease With Genital Ulcers

for the integrity of the data and the accuracy of the 2. Farhi D, Wendling J, Molinari E, et al. 6. Fistarol SK, Itin PH. Diagnosis and treatment of
data analysis. Non-sexually related acute genital ulcers in 13 lichen sclerosus: an update. Am J Clin Dermatol.
Study concept and design: Finch, Wald. pubertal girls: a clinical and microbiological study. 2013;14(1):27-47.
Acquisition, analysis, or interpretation of data: All Arch Dermatol. 2009;145(1):38-45. 7. Galeone M, Colucci R, D'Erme AM, Moretti S,
authors. 3. Huppert JS. Lipschutz ulcers: evaluation and Lotti T. Potential infectious etiology of Behçet’s
Drafting of the manuscript: Finch, Wald. management of acute genital ulcers in women. disease. Patholog Res Int. 2012;2012:595380.
Critical revision of the manuscript for important Dermatol Ther. 2010;23(5):533-540.
intellectual content: Finch, Ferenczi, Khalid, 8. di Meo N, Quaranta L, Crisman G, Trevisan G.
Murphy. 4. Letsinger JA, McCarty MA, Jorizzo JL. Complex Adamantiades Behçet disease triggered by a tick
Administrative, technical, or material support: Finch. aphthosis: a large case series with evaluation bite and or Borrelia infection. J Eur Acad Dermatol
Study supervision: Finch, Murphy. algorithm and therapeutic ladder from topicals to Venereol. 2009;23(10):1198-1199.
thalidomide. J Am Acad Dermatol. 2005;52(3, pt 1): 9. Bhate C, Schwartz RA. Lyme disease: part I.
Conflict of Interest Disclosures: None reported. 500-508. advances and perspectives. J Am Acad Dermatol.
REFERENCES 5. Berlin C. The pathogenesis of the so-called ulcus 2011;64(4):619-636.
vulvae acutum. Acta Derm Venereol. 1965;45(3):
1. Chanal J, Carlotti A, Laude H, Wallet-Faber N, 221-222.
Avril MF, Dupin N. Lipschütz genital ulceration
associated with mumps. Dermatology. 2010;221(4):
292-295.

NOTABLE NOTES

Leishmaniasis
A Disease With Many Names
Gianluca Nazzaro, MD; Marco Rovaris, MD; Stefano Veraldi, MD

Leishmaniasis is known by a myriad of popular names: Aleppo boil, “On the Possibility of the Occurrence of Trypanosomiasis in India” in the
Aleppo button, and Aleppo evil; Baghdad boil; Biskra button and Biskra British Medical Journal. In the same year, Charles Donovan, professor
nodule; Calcutta ulcer; chiclero ulcer; Delhi boil; Jericho button; Kanda- of physiology at Madras University in India, reported similar findings
har sore; Lahore sore; Oriental button and Oriental sore; Pian bois; Uta and concluded that Leishman bodies were a new parasite distinct from
for cutaneous leishmania; black fever; dum-dum fever; and Kala-azar for Trypanosoma. British physician Ronald Ross sought the link between these
visceral leishmania.1 organisms and Kala-azar and named them Leishmania donovani.
Cutaneous leishmaniasis—or Oriental sore—is an ancient disease from In the New World, the disease is believed to be autochthonous; in fact,
the Old World. The first reference was found in the Ebers Papyrus (2000 some pre-Colombian sculptures depict comparable, erosive lesions. More-
BC), an Egyptian medical papyrus in which “Nile furuncle” is named. Fur- over, Incan texts from the 15th and 16th centuries mention the presence
thermore, cutaneous leishmania may be 1 of the 12 plagues of Egypt de- of skin ulcers on seasonal agricultural workers returning from the Andes.
scribed in the Old Testament. In the 10th century, the Persian writer Avi- The lesions were attributed to the “valley sickness” or “Andean sickness,”
cennadescribedwhathecalled“Balkhsore”innorthernAfghanistan.There and later, because of the resemblance with leprosy, they were also known
is also other evidence from various places in the Middle East of an entity as “white leprosy.” In Central America (Belize, Guatemala, Mexico), cuta-
known as “Baghdad boil” or “Jericho button.” In India, visceral leishmani- neous leishmania is considered an occupational disease. It is known as
asis was known by the term Kala-azar (“black fever” in Hindi), indicative chiclero ulcer because it is endemic among forest workers who collect the
of the terrifying effect of the disease. In 1756, Alexander Russell clinically chicle latex from which chewing gum is produced.2
described the cutaneous disease in a Turkish patient and called it “Aleppo
Author Affiliations: Dipartimento di Fisiopatologia medico-chirurgica e dei
boil” owing to the ugly scar that remained after its healing. In 1885, David trapianti, Università degli Studi di Milano, Fondazione IRCCS Ca’ Granda
Douglas Cunningham, a physician of the Indian Army in Calcutta, India, de- Ospedale Maggiore Policlinico, Milan, Italy.
scribed what he thought to be the spores of an ulcer of “Delhi boil.” He pos- Corresponding Author: Gianluca Nazzaro, MD, Dipartimento di Fisiopatologia
tulated, therefore, that cutaneous leishmaniasis had a fungal etiology. In medico-chirurgica e dei trapianti, Università degli Studi di Milano, Fondazione
1898, Peter Borovsky, a Russian military surgeon working in Tashkent Mili- IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Pace 9, 20122 Milan, Italy
tary Hospital (in what is now Uzbekistan), discovered the protozoan re- (gianluca.nazzaro@gmail.com).
sponsiblefor“theOrientalsore.”Threeyearslater,WilliamLeishman,aScot- 1. Ul Bari A. Chronology of cutaneous leishmaniasis: an overview of the history
tish army doctor, identified peculiar bodies in the spleen pulp of a soldier of the disease. J Pak Assoc Dermatol. 2006;16:24-27.
who had died of “dum-dum fever,” and in 1903, he published his work 2. Abu-Laban RB. “Chiclero’s ulcer.” CMAJ. 1986;134(3):216.

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