In July 2006, a 50-year-old female presented to the dermatology clinic with a complaint of painful skin changes in her bilateral lower extremities. She was employed as a dog groomer, and her past medical history was significant for type 2 diabetes mellitus with insulin requirements, gastritis, and severe valvular heart disease affecting the tricuspid, mitral, and aortic valves with surgical repair of the aortic valve. On physical examination, the patient was found to have linear, hyperpigmented macules on the bilateral lower legs with foci of scarring and ulceration. Two biopsies of the proximal and distal left lower leg suggested livedoid vasculopathy pending clinical correlation. She was additionally found to have an elevated antithrombin 3 activity of 124 (reference range 70.0-120.0), which is strongly suggestive of an underlying prothrombotic component to her condition. At this time, therapeutic options for livedoid vasculopathy were considered and offered to the patient.
The patient's preferences and past medical history presented several obstacles to treatment of her LV. She repeatedly refused anticoagulant therapy because her husband had previously had issues with the diet restrictions and INR monitoring mandated by the use of warfarin. Antiplatelet agents were avoided due to her history of severe gastritis that was onset prior to our management of her LV. Intravenous immunoglobulin was considered; however, the patient could not afford the co-pay and her cardiologist recommended against IVIG due to the risk of these hyperosmolar preparations causing fluid overload in this patient with severe valvular heart disease. The patient was eventually started on an acceptable treatment regimen consisting of oral dapsone 100 mg once daily and prednisone 10 mg once daily, with the addition of doxepin or tramadol for intermittent pain control. With these medications, she achieved intermittent remission of her LV for several years.
In 2015, she began having intermittent, painful flares of her LV which were managed by increasing her dapsone to 150 mg once daily and increasing her prednisone to 20 mg. She sometimes required burst doses of 60 mg once daily. Attempts to wean her prednisone back down to 10 mg were rarely successful, and this dosing became an ongoing concern in 2018 when she began having severe hyperglycemic episodes which resulted in a brief hospitalization. Her insulin delivery was also switched to a pump system.
In the fall of 2018, she presented to dermatology during an acute LV pain flare and was coincidentally found to have an erythematous papule at the right dorsal forearm, which she attributed to a possible insect bite or a scratch from her dog. Three weeks later, she reported worsening of this right forearm lesion as well as new onset of two painful, ulcerative lesions on her right thigh and right forearm. On examination, the right dorsal forearm was now found to have two firm, tender erythematous papulonodules, one with central ulceration (Figure 1). The right lateral thigh was found to have a single purpuric patch with central ulceration and necrosis (Figure 2). The bilateral forearms additionally had a few scattered linear superficial abrasions consistent with animal scratches. No other new lesions were found on examination. She perceived these lesions as dissimilar from her typical LV, but at this time mycophenolate mofetil 500 mg twice daily was added for her ongoing LV flares. A 4 mm punch biopsy of a right dorsal forearm lesion revealed suppurative, granulomatous inflammation in the deep reticular dermis with demonstration of acid-fast organisms on AFB stain (Figure 3).
The patient was subsequently evaluated for systemic mycobacterial disease. A chest X-ray showed no evidence of pulmonary mycobacterial disease. Laboratory testing was negative for HIV, AFB blood culture, and Tb QuantiFERON. Her CRP was elevated at 13.3, and the CBC revealed a mild leukocytosis of 13.00 with mild neutrophilia of 79.4%, elevated absolute neutrophils (10.3), and absolute immature granulocytes (0.4).
The state Department of Health identified rapidly growing Mycobacterium abscessus/chelonae on her right forearm tissue culture. Susceptibility testing and treatment guidance was subsequently provided by a national center specializing in mycobacterial consultation. Susceptibility results revealed resistance to cefoxitin, doxycycline, sulfamethoxazole-trimethoprim, and amoxicillin-clavulanic acid and sensitivity to clarithromycin, azithromycin, linezolid, imipenem, and amikacin. There was also intermediate sensitivity to ciprofloxacin and moxifloxacin.
The physicians of the Dermatology and Infectious Disease departments then coordinated management of her simultaneously flaring livedoid vasculopathy and disseminated cutaneous mycobacterial infection. The patient had a PICC line placed for her antimycobacterial regimen which consisted of oral azithromycin 250 mg once daily, intravenous imipenem 500 mg every 12 hours, and finally intravenous amikacin 12-15 mg/kg on Mondays, Wednesdays, and Fridays. Additional treatment with fluoroquinolones was not considered because she had a previously documented allergic reaction of a blistering skin eruption. This regimen was initially to be continued for a total of 8-12 weeks depending on her response, followed by oral azithromycin monotherapy for at least an additional 6 months. Lifelong suppression with oral monotherapy is also being considered pending her clinical response and tolerance to azithromycin.
At 10 weeks of treatment her physical exam revealed improvement of the ulcers of the right forearm, right thigh, and left foot. However, she also developed three new left knee ulcers consistent in appearance with her other mycobacterial lesions. For this reason, her current regimen is to be continued until her follow-up appointment for PICC line removal at 17 weeks of treatment. At that time, she will transition to daily maintenance therapy of oral azithromycin if she demonstrates adequate improvement in the existing lesions.
Meanwhile, the treatment of her livedoid vasculopathy was optimized by the dermatology team. Her prednisone was tapered down to 10 mg once daily, and both the dapsone and mycophenolate mofetil were discontinued. She has since been started on warfarin 1 mg once daily. This low dose was chosen due to reports of supratherapeutic INR from interaction of warfarin and azithromycin. Her LV was found to be stable at her follow-up appointment 9 weeks after initiating and continuing the same dose of warfarin.