DIAGNOSTIC DILEMMA Thomas J. Marrie, MD, Section Editor
Inner Peace: Cutaneous Polyarteritis Nodosa Konstantinos Parperis, MD,a,b Fawad Rast, MDc a c
Division of Rheumatology, Department of Medicine, University of Arizona College of Medicine, Tucson; bDivision of Rheumatology and Department of Internal Medicine, Maricopa Medical Center, Maricopa Integrated Health System, Phoenix, Ariz.
PRESENTATION Skin discoloration indicated that the patient had a vascular disorder, but her prognosis proved better than might have been expected. A 42-year-old Hispanic woman presented with a worsening, painful rash on both lower extremities. Her symptoms began 4 months earlier as a pruritic, erythematous rash around her ankles. It then spread to the rest of her body, including her palms, soles, and face. She subsequently developed arthralgia in her knees, wrists, and hands. The patient was first seen at an outside facility, where a skin biopsy was performed. Nonspecific findings of spongiotic dermatitis with superficial perivascular chronic inflammation were revealed. She was treated with a short course of prednisone, 10 mg daily. Her skin lesions and joint pain improved, but 1 month prior to admission at our hospital, the rash recurred and was associated with painful, necrotic skin lesions. She had no significant past medical history.
ASSESSMENT On initial evaluation, the patient’s temperature was 36.3 C (97.3 F), her pulse rate was 93 beats per minute, and her blood pressure was 112/70 mm Hg. Her respiratory rate was 16 breaths per minute with an oxygen saturation of 98% on ambient air. Features of livedo racemosa and retiform purpura were seen on both of the patient’s upper and lower extremities (Figure 1). The results from a complete blood count and basic metabolic panels were within normal limits. Her erythrocyte sedimentation rate (96 mm/h) and C-reactive protein level (32.48 mg/dL) were elevated. Funding: None. Conflict of Interest: None. Authorship: Both authors were involved in the conception and design of the study, acquisition of data, data analysis, and the drafting, revision, and approval of the final version of the manuscript. Requests for reprints should be addressed to Fawad Rast, MD, Department of Internal Medicine, Maricopa Medical Center, 2601 East Roosevelt Street, #OD10, Phoenix, AZ 85008. E-mail address:
[email protected] 0002-9343/$ -see front matter Ó 2017 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjmed.2017.02.006
Determining the cause of retiform purpura, the most concerning of the patient’s lesions, can be difficult. The differential diagnosis is broad and includes vasculitis, antiphospholipid syndrome, calciphylaxis, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, warfarin-induced necrosis, and myeloproliferative disorders.1 An autoimmune work-up disclosed an elevated gamma globulin level of 2.1 g/dL on serum protein electrophoresis and low levels of complements 3 and 4. Tests for antinuclear antibodies, antineutrophilic cytoplasmic antibodies, myeloperoxidase antibody, serine proteinase 3 antibody, rickettsia antibody, and human immunodeficiency virus antibody were all negative. Similarly, a hepatitis panel, a Quantiferon-TB Gold in-tube test (Quest Diagnostics, Madison, NJ), a rapid plasma reagin titer, and blood cultures were negative.
DIAGNOSIS Because the work-up at the first hospital was inconclusive, a new skin biopsy was performed. This time, a neutrophilic infiltrate with leukocytoclastic debris surrounded small- and medium-sized vessels within the superficial and deep dermis; fibrin deposition and vascular necrosis were evident as well (Figures 2-4). The findings were consistent with polyarteritis nodosa. Computed tomography angiography of the patient’s abdomen and pelvis did not show vascular stenosis, aneurysm, or ischemic lesions in the internal organs. On the basis of her presentation, biopsy results, and the lack of evidence of systemic involvement, a diagnosis of cutaneous polyarteritis nodosa was made. Cutaneous polyarteritis nodosa, a rare form of vasculitis in small- to medium-sized arteries, was first recognized as a variant restricted to the skin in 1931.2,3 An assortment of lesions, including subcutaneous nodules, livedo reticularis, livedo racemosa, retiform purpura, and ulcers, mainly form on the lower extremities, and no internal organs are injured.4 Retiform purpura, the net-like pattern of red-purple necrotic lesions, can be the first manifestation of the disease.1,5 It occurs when blood flow to the dermal and subcutaneous vasculature is occluded.
Parperis and Rast
Cutaneous Polyarteritis Nodosa
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Figure 3 A biopsy sample was also obtained from the right medial knee. Necrosis was identified in a medium-sized artery.
histopathologic findings in the skin lesions; notably, segmentary leukocytoclastic vasculitis in the smallto medium-sized arteries of the deep dermis or hypodermis.11
MANAGEMENT Figure 1 Features of livedo racemosa and retiform purpura were evident on the patient’s legs.
Although the pathogenesis of cutaneous polyarteritis nodosa remains unknown, deposition of immune complexes and complement activation within the arterial walls are thought to be components.6,7 Among possible triggers are hepatitis B and C infections, inflammatory bowel disease, parvovirus B19, Mycobacterium tuberculosis, streptococcal infections, and certain medications, such as minocycline.8-10 Our patient’s case appears to have been idiopathic. No specific tests are available, so diagnosis is based on the patient’s clinical symptoms and
Figure 2 A punch biopsy was performed on the right medial lower leg. Prominent fibrin deposition was seen within a blood vessel.
Unlike systemic polyarteritis nodosa, the cutaneous form has a more favorable prognosis, and while it is possible for patients to develop the systemic features of the disease, most do not.5 First-line treatment includes nonsteroidal antiinflammatory drugs, colchicine, and topical or low-dose oral steroids. Patients with refractory and severe symptoms can receive glucocorticoids in dosages up to 1 mg/kg daily.11 Our patient was initially treated with prednisone, 60 mg daily, with a weekly taper. However, her cutaneous lesions recurred after the prednisone dosage was reduced below 10 mg daily. As a result, mycophenolate mofetil was added to her regimen, and a few weeks later, we were able to taper her off the prednisone with excellent control of her symptoms. She remained on the mycophenolate, though at this time, there are insufficient data to define the most effective mode and duration of treatment. The disease is chronic, so she may experience relapses.
Figure 4 The same necrotic, medium-sized artery in the knee is shown here at higher magnification.
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The American Journal of Medicine, Vol 130, No 7, July 2017 6. Diaz-Perez JL, Schroeter AL, Winkelmann RK. Cutaneous periarteritis nodosa: immunofluorescence studies. Arch Dermatol. 1980;116(1):56-58. 7. Kawakami T, Yamazaki M, Mizoguchi M, Soma Y. High titer of antiphosphatidylserinee prothrombin complex antibodies in patients with cutaneous polyarteritis nodosa. Arthritis Rheum. 2007;57(8):1507-1513. 8. Ramos F, Figueira R, Fonseca JE, et al. Juvenile cutaneous polyarteritis nodosa associated with streptococcal infection. Acta Reumatol Port. 2006;31(1):83-88 [in Portuguese]. 9. Whittaker SJ, Dover JS, Greaves MW. Cutaneous polyarteritis nodosa associated with hepatitis B surface antigen. J Am Acad Dermatol. 1986;15(5 Pt 2):1142-1145. 10. Culver B, Itkin A, Pischel K. Case report and review of minocyclineinduced cutaneous polyarteritis nodosa. Arthritis Rheum. 2005;53(3): 468-470. 11. Bauzá A, España A, Idoate M. Cutaneous polyarteritis nodosa. Br J Dermatol. 2002;146(4):694-699.
