A case of a recalcitrant painful skin ulceration

Case report

A 57‐year‐old African American female with a past medical history of avascular necrosis of the bilateral hips and shoulder, longstanding smoking, miscarriage, diabetes, chronic kidney disease, and hepatitis C presented for a several months' history of an extremely painful ulceration on her right lateral malleolus (Figure 1). The patient described the lesion as worse in the summertime. She was previously treated with topical and systemic steroids and antibiotics with no improvement. Physical exam revealed a tender stellate deep ulcer overlying the right lateral malleolus with peripheral hyperpigmentation and pinpoint white scarring. Serology was notable for elevated levels of ANA, C4, lipoprotein A, and rheumatoid factor levels, with a heterozygous mutation of the MTHFR A1298C.

Figure 1.

Ulceration of the right lateral malleolus

Histopathology showed hyalinization and focal fibrin deposition within the small vessel wall, vascular congestion and extravasated red blood cells within the deep dermis, and focal thrombosis at the interface of the deep dermis and subcutaneous tissue (Figure 2). The patient was started on high potency topical steroids, aspirin 325 mg daily, indomethacin 25 mg twice daily, and doxycycline 100 mg twice daily. Smoking cessation was strongly advised and, after a doppler ultrasound and a normal ankle‐brachial index of 0.99 ruled out any underlying arterial compromise, compression stockings were also recommended. A follow‐up visit at 2 months showed remarkable ulcer improvement and resolution in her pain (Figure 3).

Figure 2.

Histologic tissue sample from the ulcer at the right lateral malleolus demonstrated hyalinization and focal fibrin deposition within the small vessel wall leading to thickening (box), vascular congestion and extravasated red blood cells within the deep dermis, and focal thrombosis (arrow) at the interface of the deep dermis and subcutaneous tissue. (Hematoxylin and eosin, ×400)

Figure 3.

Healing ulceration of the right lateral malleolus

What is your diagnosis: A) Polyarteritis nodosa, B) Cryoglobulinemia, C) Livedoid vasculopathy, or D) Ischemic ulcer

Diagnosis

C. Livedoid vasculopathy.

Discussion

Livedoid vasculopathy (LV) was originally described as atrophie blanche en plaque by Milian in 1929; however, it is also known as livedo reticularis with summer ulcerations, livedoid vasculitis, livedo vasculitis, and segmental hyalinizing vasculitis. ¹ Similar to our patient, the classic patient is a middle‐aged female with exquisitely painful purpuric plaques or papules that often progress to ulcerations overlying the malleoli, often with a background of livedo reticularis or retiform purpura, suggesting an underlying vasculopathy. Just as our patient's ulcer onset occurred in the summertime, LV tends to flare during warm temperatures. Lesions heal with porcelain‐white scarring with surrounding telangiectasias, known as atrophie blanche. ² LV more commonly occurs in young adult females, possibly due to sex‐specific physiologic conditions such as pregnancy, connective tissue disorders, and inherited coagulation abnormalities. ³

The pathogenesis of LV is not entirely clear but likely hinges on aberrancies in coagulation leading to thrombus formation in dermal microcirculation and subsequent ischemia and infarction, with little to no perivascular inflammation. In accordance, histopathology reveals dermal vessels with thrombosis, vessel wall thickening, endothelial proliferation, and hyaline degeneration of the subintimal layer. ⁴ Reaching a diagnosis of LV requires both clinical and pathologic correlation. Once a diagnosis is reached, interdisciplinary collaboration with hematology/oncology colleagues is critical in addressing the underlying coagulation disorder. Our patient's history of avascular necrosis of both hips, and shoulder requiring several replacement and arthroplasty surgeries as well as miscarriages, underscore how the diagnosis of LV is often delayed and requires interdisciplinary collaboration.

A systematic review of the association of genetic variants and LV in 256 patients identified the MTHFR A1298C mutation, the variant present in our patient, as the fourth most commonly associated mutation. ⁵ Mutations in MTHFR may lead to hyperhomocysteinemia, which promotes a pre‐thrombotic state due to endothelial cell damage by homocysteine. For this reason, we believe mutation analysis testing is an appropriate step in determining the etiology of LV in a patient. Treatment for livedoid vasculopathy includes managing the patient's pain, proper wound care, pharmacotherapy and recommending smoking cessation. A recent systematic review of 339 LV patients found that anticoagulants were the most commonly prescribed monotherapy, and this therapy achieved a favorable response in 98% of patients. ⁶ Anabolic steroids, intravenous immunoglobulins, and antiplatelets were the second, third, and fourth most commonly employed treatments, respectively. ⁶ A search of the literature did not reveal how the prognosis of LV associated with mutations in the MTHFR gene compares to primary LV or other secondary causes of the disease.

Our case is a classic example of LV, a rare disease where dermatologists can play a critical role in early diagnosis and intervention, as well as in screening and addressing any associated underlying hypercoagulable state. We theorize that our patient's MTHFR mutation aided in the development of her disease. Unfortunately, due to economic barriers, the patient was unable to see rheumatology to pursue further workup and has lost follow‐up with our clinic. While the vast majority of reported cases of LV are in lighter skin phototypes, we hope that this case of LV in a skin of color patient will add to the image repository and aid dermatologists in improving competency in reaching a diagnosis in all skin types.