Vasculitis on the run

By Warren R. Heymann, MD, FAAD
July 10, 2024
Vol. 6, No. 28

I am not a runner, but I live vicariously through my residents who are. This weekend, our first-year resident, Erika Tvedten, will run the Philadelphia marathon for the first time. I have been intrigued (and impressed!) by her compulsive devotion to her training schedule. After rounds last week, she informed me that she will also run the Black Canyon 100K (62 miles) Ultramarathon at the Sonoran Desert trails in the shadow of Arizona’s Bradshaw Mountains. To each their own — I was proud of completing the 2-mile Cooper-Norcross “Run/Walk the Bridge” event last weekend on the Ben Franklin Bridge between Camden and Philadelphia, with a personal best power walk of 30 minutes — Black Canyon, here I come!

Two days after the walk, I read a case report entitled “Bilateral lower extremity inflammatory lymphedema” by Robinson et al. (1), which I forwarded to Erika. (We want to keep our residents healthy!) The disorder inspired this commentary, but important background information must be addressed first.

In 2004, Ramelet discussed the concept of “exercise-induced purpura” in the following abstract:

Exercise-induced purpura (EIP) occurs on the lower legs after unusual or major muscular activity, as in marathon runners or as after long walks, especially in the mountains in hot weather. In leisure walkers, patients are otherwise healthy females. There is no relation with chronic venous disorder. Erythematous, urticarial or purpuric plaques arise on the lower leg, usually sparing the skin compressed by socks. Symptoms include itch, pain and a burning sensation. Histopathology demonstrates leukocytoclastic vasculitis. The lesions fade after some days, with frequent relapses at further muscular exercises and may be prevented in some cases by compression, intake of venoactive drugs and local application of steroids. EIP is not uncommon, even if very few descriptions have yet been published. It appears to be consecutive to venous stasis induced by an acute failure of the muscle pump of the calf and thermoregulation decompensation, after a prolonged and unusual exercise, such as running or walking in hot weather. (2)

Ramelet subsequently reported 23 otherwise healthy patients (22 females, 1 male) who developed lesions after walking or hiking in hot weather. Erythematous, urticarial, or purpuric plaque appeared on the lower legs, sparing areas compressed by socks. Symptoms included itch, pain, and a burning sensation. Lesions resolved within days. Relapses frequently occurred with further exercise and could be prevented in some cases by compression hosiery, manual lymphatic drainage, intake of edema protective agents, or steroids (local or systemic). Histopathology demonstrated leukocytoclastic vasculitis in five biopsies and urticarial vasculitis in one. Systemic investigations were negative in the six patients tested. There was no apparent relation with chronic venous disease. He concluded by naming the disorder “exercise-induced vasculitis” (EIV). (3)

Kelly et al. reported “Golfer’s vasculitis” (GV) in 2005. Seventeen cases were detailed. The eruption developed in 15 after playing 18 holes of golf and in three following prolonged hikes. The rash would usually develop over the summer months under hot conditions. Most patients were over 50 years of age when the tendency to develop the eruption began. Biopsies of the rash in the active phase showed leukocytoclastic vasculitis. The authors concluded that GV represents a leukocytoclastic vasculitis induced by prolonged exercise under hot conditions in healthy people, thereby negating the need for an extensive evaluation for vasculitis.

Paul and Scalzi reached the same conclusion after describing EIP in children (aged 5 to 15 years), most of whom had an erythematous purpuric rash above the sock line extending to the knees, associated with warm weather and prolonged activity. The authors acknowledge that EIP could be mistaken for Henoch-Schonlein purpura or as a manifestation of systemic vasculitis. Although a systemic work-up for vasculitis is unnecessary in classical cases, it should be considered with atypical cases (unusual location, systemic symptoms, or a prolonged duration). (5) Other authors contend that a vasculitis work-up should be performed, even in patients with a history suggestive of activity-induced vasculitis and a negative review of symptoms. (6) My approach to GV (I tend to use that imperfect term) is reassurance and observation. This summer, an anxious patient returned from her European tour, having been on her feet in scorching heat, distraught over the purpura on her legs. A careful explanation and rest were the elixir for her skin and psyche.

Li et al. offer a cogent summation of GV: “The etiology of golfer’s vasculitis is unknown. It is likely multifactorial and related to excessive heat production during prolonged exercise, leading to muscular hyperthermia and tissue damage, exercise-related immune system alteration, venous stasis, and alterations in skin blood flow. Histological features on skin biopsy range from urticarial vasculitis with eosinophils to typical leukocytoclastic vasculitis. Complement components C3 and C1q, immunoglobulin IgM, fibrinoid necrosis deposition, and erythrocyte extravasation can be present as well.” (7)

Fajardo et al. reported 55 Air Force basic trainees who developed bilateral lower extremity inflammatory lymphedema (BLEIL) during an 8.5-week basic training course. Fifty-four of the 55 incident cases (98%) of BLEIL occurred during the first 120 hours of training. (8) BLEIL presents with exquisite tenderness, erythema, and edema of the lower leg, ankle, and dorsal foot, resembling acute cellulitis. Histologic studies have confirmed leukocytoclastic vasculitis; direct immunofluorescence demonstrates C3 but is negative for IgG, IgA, or IgM. The presumption is that the lymphedematous changes are secondary. (9) The case of BLEIL presented by Robinson was a 54-year-old man who developed symptoms a few hours after finishing a 100-mile trail-running race. (He reported running continuously for > 30 hours!) His warm, swollen, distal legs were not purpuric (see image). A mild elevation of creatine kinase accompanied the disorder. Significant improvement was noted within 9 days of prescribed leg compression and elevation. (1)

Two days after the walk, I read a case report entitled “Bilateral lower extremity inflammatory lymphedema” by Robinson et al.

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After reviewing the literature, I suspect that EIV (EIP, GV) and BLEIL are on a spectrum of benign cutaneous leukocytoclastic vasculitis.

Mark Twain said, “I have never taken any exercise, except sleeping and resting, and I never intend to take any. Exercise is loathsome. And it cannot be any benefit when you are tired; I was always tired.” For those who push the envelope, however, entities such as EIV (EIP, GV) and BLEIL may be a reality, but fortunately, only a nuisance.

Point to Remember: Vigorous exercise may induce a self-limited cutaneous leukocytoclastic vasculitis, including the recently described bilateral lower extremity inflammatory lymphedema.

Our expert’s viewpoint

Chad Hivnor, MD, FAAD
Chief of Dermatology
South Texas Veterans Health Care System; U.S. Department of Veterans Affairs
Clinical Associate Professor Uniformed Services University Health Sciences

When you see that patient with cutaneous leukocytoclastic vasculitis (LCV) I personally mention to patients that there are hundreds of reasons to have that inflammation and reaction pattern. Dr. Heymann points out yet another, one we had extensive experience with Basic Trainees entering the Air Force. (8) We described it as bilateral lower extremity inflammatory lymphedema (BLEIL) but is likely the same thing as the LCV from golfing, running, or exercise. The Air Force had their epidemiology team explore the vast number of variables amongst our patients and found no specific trigger. This benign self-resolving condition eludes us yet again and again as some dermatologic conditions do.

At one point we just stopped performing biopsies on patients because it was the same pattern repeatedly and biopsies of the foot and ankle area do not heal well, especially when you want to get the patient back to basic training. There would be clusters of activity where, again, triggers could not be determined. Our team reported from a histologic perspective showing the LCV was in the deep vascular plexus. (9) This deeper involvement led to more of a lymphedematous and cellulitis picture. I have always felt there was a pressure related induction of inflammation analogous to dermatographism or pressure induced urticaria. Subtle at first, but with prolonged and persistent trauma this increases. Prolonged standing was the only thing common, yet this is a frequent occurrence in basic trainees. You can see this in prolonged exposures when individuals are in physical shape or with short exposures in those that may not be conditioned for that exercise. But this is conjecture based upon being a previous runner and with our experience in the basic trainees. Future endeavors should look at the specifics of prolonged standing, calf pump failure, immune complex deposition and a true vasculitis.

Supportive care was the most effective modality of improvement: compression and elevation. I personally felt that daily use of clobetasol ointment may have shortened the course in some cases.

1. Robinson WH, Willardson HB, Nye NS. Bilateral lower extremity inflammatory lymphedema after an ultramarathon. JAAD Case Rep. 2023 August 9;40:145-147. doi: 10.1016/j.jdcr.2023.08.002. PMID: 37817887; PMCID: PMC10562084.

2. Ramelet AA. Exercise-induced purpura. Dermatology. 2004;208(4):293-6. doi: 10.1159/000077837. PMID: 15178910.

3. Ramelet AA. Exercise-induced vasculitis. J Eur Acad Dermatol Venereol. 2006 Apr;20(4):423-7. doi: 10.1111/j.1468-3083.2006.01504.x. PMID: 16643140.

4. Kelly RI, Opie J, Nixon R. Golfer's vasculitis. Australas J Dermatol. 2005 Feb;46(1):11-4. doi: 10.1111/j.1440-0960.2005.00127.x. PMID: 15670170.

5. Paul SS, Scalzi LV. Exercise-Induced Purpura in Children. Pediatrics. 2019 Apr;143(4):e20182797. doi: 10.1542/peds.2018-2797. Epub 2019 March 7. PMID: 30846618.

6. Garg A, Goldberg D. Relapsing leukocytoclastic vasculitis triggered by activity in a young woman. Arch Dermatol. 2009 May;145(5):601-2. doi: 10.1001/archdermatol.2009.66. PMID: 19451515.

7. Li W, Moran A, Kim ES. Golfer's vasculitis. Vasc Med. 2019 Jun;24(3):265-266. doi: 10.1177/1358863X18820121. Epub 2019 February 27. PMID: 30813867.

8. Fajardo KA, Keller P, Kobayashi T, Hivnor CM, Webber BJ, Federinko SP, Tchandja J. Bilateral lower extremity inflammatory lymphedema in Air Force basic trainees: clinical and epidemiologic study of a new disease entity. JAMA Dermatol. 2015 Apr;151(4):395-400. doi: 10.1001/jamadermatol.2014.3794. PMID: 25607253.

9. McCann SE, Dalton SR, Kobayashi TT. Histopathology of bilateral lower extremity inflammatory lymphedema in military basic trainees: A leukocytoclastic vasculitis of the deep vascular plexus. J Cutan Pathol. 2017 May;44(5):500-503. doi: 10.1111/cup.12918. Epub 2017 March 8. PMID: 28195354.

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