Lipschütz ulcers: Not only for women
By Warren R. Heymann, MD
March 24, 2021
Vol. 3, No. 12
Superstar dermatologists do not throw softball questions to presenters at the Annual Meeting of the American Academy of Dermatology. A few years ago, following my presentation on the cutaneous manifestations of Epstein-Barr infection, Dr. Jeffrey Callen, one of the world’s premier dermatologists, asked me “why don’t Lipschütz ulcers (LU) appear in boys?” All I could do was shrug my shoulders. Dr. Callen, I can now give you a better answer.
LU (aka ulcus vulvae acutum, non-sexually related acute genital ulcers) are painful ulcerations of the external genitalia occurring primarily in adolescent females, with a mean age of onset of 14.5 years. They are often misdiagnosed as herpes simplex virus infection or Behçet disease, and may prompt an evaluation for sexual abuse, causing significant physical and emotional distress for the patient and parents. Nonspecific prodromal symptoms, including fatigue, anorexia, headache, and low-grade fever, often precede the appearance of ulcers. Patients typically present with ≥1 very painful ulcer with characteristic purple-red ragged edges, most commonly on the medial or outer surface of the labia minora. To date EBV is the most commonly identified infectious cause. LU related to EBV usually occur as a solitary episode, a feature that distinguishes them from herpes and aphthosis, which tend to be recurrent. Other infectious agents implicated include CMV, Mycoplasma pneumoniae, mumps, group A Streptococcus, Salmonella, Toxoplasma, and influenza A virus. (1)
Based on 60 cases of LU derived from 21 publications, Sandoghi et al proposed the following diagnostic algorithm for LU defined by two major and four minor criteria. The major criteria are:
acute onset of one or more painful ulcerous lesions in the vulvar region and;
exclusion of infectious (notably herpes, primary syphilis, chancroid, etc.) and non‐infectious causes for the ulcer (Beçhet, autoimmune bullous disease, Crohn disease, etc.).
The minor criteria are:
localization of ulcer at vestibule or labia minora;
no history of sexual intercourse (i.e. either virginal status or no sexual intercourse within the last 3 months);
flu‐like symptoms; and/or
systemic infection within 2–4 weeks prior to onset of vulvar ulcer.
If both of the major criteria and at least 2 of the minor criteria are invoked, then a diagnosis of LU is warranted. (2)
Some readers of DWI&I have noticed that I appreciate medical articles with intriguing titles. I had to read further when I happened upon “Juvenile gangrenous vasculitis of the scrotum — a diagnosis not to forget.” You cannot forget something you never knew in the first place. What is juvenile gangrenous vasculitis of the scrotum (JGVS)?
Gomes et al described the case of an 18-year-old man in good health who presented with rapidly developing scrotal ulcers unaccompanied by lymphadenopathy; 5 days earlier he had pharyngitis treated with amoxicillin/clavulanic acid. Laboratory studies (appropriate bacteriologic, PCR, and serologic) were negative for syphilis, HSV, EBV, CMV, and parovirus B19. A neutrophilia was noted on his CBC. A biopsy demonstrated a neutrophilic infiltrate without frank leukocytoclastic vasculitis. The ulcers resolved completely without scars in a month. (3)
In their reply to Gomes et al, Jiminez-Cauhe et al state: “JGVS was described in 1974 by Piñol et al., and it remains a rare and barely known entity. However, it has a very recognizable presentation with specific features, and it is probably under‐ or misdiagnosed. It presents as acute scrotal ulcers in young and healthy men, nonsexually related (both in history and microbiological investigations), preceded and/or accompanied by an infectious prodrome with fever (mainly tonsillitis) and elevated acute phase reactants. This presentation is particularly similar to Lipschütz ulcers in women, a widely known entity among dermatologists.” They presented 5 cases (3 from a prior publication); importantly only one had evidence of EBV infection. They also noted that the histologic term vasculitis may be misleading as the histology tends to be non-specific. (4)
The etiology of JGVS is obscure but is likely a reactive phenomenon to an infectious etiology in predisposed patients. Caputo et al questioned if the entity is a variant of pyoderma gangrenosum (PG). (5) The fact that surgical debridement had a good result without pathergy in an 18-year-old man with JGVS mitigates against a diagnosis of PG. The authors note that surgery is not recommended as first-line therapy — they were considering Fournier gangrene as a diagnosis (which usually is observed in obese, diabetic men > 50 years old). (6) Most patients have been treated with antibiotics and steroids in the literature. It is not clear (to me) what treatment is optimal – certainly if there is any treatable documented infection, that should be addressed. Appropriate pain management and steroids (systemic or topical) may be valuable. There is no existing literature regarding other therapies for aphthous-like disorders (e.g., colchicine, apremilast, calcineurin inhibitors, etc.) Regardless, lesions will heal spontaneously and not recur.
The term JGVS is problematic for several reasons: 1) although patients are mostly young adults, the condition may be observed into middle age; 2) gangrenous implies a more severe prognosis; and 3) most cases are not frank vasculitis. Perhaps the simplest approach is considering JGVS as the male counterpart of the Lipschütz ulcer. I steadfastly concur with the conclusion reached by Chen and Plewig in their comparison of LU to JGVS: “We propose to denote Lipschütz genital ulcer to describe the acute excruciating genital ulcers of first‐time onset with self‐limited non‐recurrent course in association with gravely symptomatic systemic infections, in women as well as in men, in which a primary EBV infection is probably the most common aetiology.”
Residents and junior faculty understandably worry about not knowing the answers to questions posed to them following their presentations. My advice is to take a deep breath and say: “That’s a great question, and I don’t know the answer. I will look into it and get back to you.” Dr. Callen, I’m sorry it took so long.
Point to Remember: Juvenile gangrenous vasculitis of the scrotum should be recognized as the probable male equivalent of the Lipschütz ulcer.
Our expert’s viewpoint
Jeffrey Callen, MD
Chief, Division of Dermatology
University of Louisville
I am flattered that Dr. Heymann has considered me to be a “premier” dermatologist. I have always merely tried to be inquisitive, asking questions regarding issues that did not seem clear to me and attempting to get answers from the literature or from clinical or basic studies that could be easily designed and performed.
I asked Warren the question because I had recently seen a teenage boy on consultation at our children’s hospital with several scrotal necrotizing ulcers and cultures for HSV, bacteria, etc. were negative. He had recently had infectious mononucleosis and I felt that this was a Lipschütz ulcer, but all the literature at the time defined LU as something that occurred in women. His disease was self-limited and shortly after discharge we lost him to follow-up.
As Dr. Heymann has so elegantly discussed, the name for scrotal ulcers is problematic. I agree with his conclusion and the assessment from our colleagues in Europe, that this is a similar process to the Lipschütz ulcer but occurring in men.
Dr. Callen had disclosed financial relationships with the following to the AAD at the time of publication: Abbott Laboratories, AbbVie, Allergan, Inc, Amgen, Arena Pharmaceuticals, Celgene, CVS/Caremark, Elsevier Inc., Johnson and Johnson, Merck & Co., Inc, Pfizer Inc., Principia Biopharma Inc, Procter & Gamble Company, 3M Pharmaceuticals, UpToDate, Inc. Full disclosure information is available at coi.aad.org.
Hall LD, Eminger LA, Hesterman KS, Heymann WR. Epstein-Barr virus: Dermatologic associations and implications. Part I. Mucocutaneous manifestations of Epstein-Barr virus and nonmalignant disorders. J Am Acad Dermatol 2015; 72: 1-19.
Sadoghi B, Stary G, Wolf P, Komericki P. Ulcus vulvae acutum Lipschütz: A systematic literature review and a diagnostic and therapeutic algorithm. J Eur Acad Dermatol Venereol 2019 Dec 19. doi: 10.1111/jdv.16161. [Epub ahead of print]
Gomes N, Costa-Silva M, Nogueira A, Marques A, et al. Juvenile gangrenous vasculitis of the scrotum – a diagnosis not to forget. Int J Dermatol 2020; 59: e49-e50.
Jiminez-Cauhe J, Buendia-Castaño D, Ferrer-Gomez A, Prieto-Barrios M, Fernandez-Nieto D. Reply to “Juvenile gangrenous vasculitis of the scrotum – a diagnosis not to forget”. Int J Dermatol 2020 Mar 1. doi: 10.1111/ijd.14842. [Epub ahead of print]
Caputo R. Marzano AV, Di Benedetto A, Ramoni S, Camgiaghi S. Juvenile gangrenous vasculitis of the scrotum: Is it a variant of pyoderma gangrenosum? J Am Acad Dermatol 2006; 55: S50-53.
Nettleton J, Crawford-Smith H, Adimonye A, McMeekin F. Scrotal necrosis and Fournier’s in sight: A rare case of juvenile gangrenous vasculitis. BMJ Case Rep 2019 Feb 21;12(2). pii: e226530. doi: 10.1136/bcr-2018-226530.
Chen W, Plewig G. Lipschütz genital ulcer revisited: Is juvenile gangrenous vasculitis of the scrotum the male counterpart? J Eur Acad Dermatol Venereol 2019; 33:1660-1666.
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