Published on 19/03/2015 by admin
Filed under Dermatology
Last modified 22/04/2025
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Cindy E. Owen and Jeffrey P. Callen
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
Polyarteritis nodosa (PAN) is a necrotizing vasculitis that involves small or medium-sized arterioles. Classic PAN is characterized by fever, weight loss, cutaneous ulcers, livedo reticularis, myalgias and weakness, arthralgias or arthritis, neuropathy, abdominal pain, ischemic bowel, testicular pain, hypertension, and renal failure. Microscopic polyarteritis (MPA) involves the same-sized vessels as well as smaller vessels, and is manifest clinically as a glomerulonephritis and a pulmonary capillaritis with alveolar hemorrhage. Patients with MPA may develop small vessel vasculitis (palpable purpura), livedo reticularis with or without nodules, and/or ulcerations of the skin. Cutaneous PAN (cPAN), sometimes termed benign cutaneous polyarteritis, is characterized by livedo reticularis, nodules and ulceration, usually of the leg; it has been postulated to be a localized necrotizing arteritis that does not affect internal organs, and runs a chronic but benign course. Many reports, however, have linked cPAN to inflammatory bowel disease, streptococcal upper respiratory infection, or hepatitis B or C infection. Occasional reports have linked cPAN to antiphospholipid antibodies, cryoproteins, or antineutrophil cytoplasmic antibodies. One recent report has demonstrated that interleukin-6 is elevated in roughly 40% of patients (Kawakami, T., et al., 2012. Acta Derm Venereol 8;92 (3), 322–323). Some cases have occurred in patients treated with propylthiouracil and minocycline. cPAN appears to be more prevalent in children. Although it is generally benign, there have been reports of associated neuropathy, as well as visceral involvement.
cPAN causes pain and discomfort and may ulcerate, thereby causing disability. Therapy may include local measures, e.g., gradient pressure stockings, or systemic therapies, including systemic corticosteroids, methotrexate, azathioprine, pentoxifylline, and intravenous immuneglobulin (IVIG). Most of the reports are anecdotes or small case series.
Skin biopsy
Serology for hepatitis B and C, anti-streptolysin O antibody titers, antineutrophil cytoplasmic antibodies, antiphospholipid antibodies, and cryoproteins
Assessment for systemic involvement
Assessment for inflammatory bowel disease
Assessment for drugs that have been linked to cPAN
Daoud MS, Hutton KP, Gibson LE. Br J Dermatol 1997; 136: 706–13.
This retrospective analysis of 79 patients evaluated the clinical and histological features of cPAN and attempted to identify any clinical, pathological, and immunological differences that may distinguish those cases likely to have a prolonged course. During the course of their illness 39 patients had ulcers. Women were affected more than men. Painful nodules on the lower extremities, with edema and swelling, were the most common clinical finding; 22% of patients had some evidence of neuropathy. Most of the laboratory findings were non-specific. There was no evidence for hepatitis B infection in the 37 patients tested, and hepatitis C infection was present in only one of the 20 patients tested. Five patients had inflammatory bowel disease (four had Crohn disease and one had ulcerative colitis). Ten patients had rheumatoid arthritis. Most patients (60%) had no associated medical condition. The disease course was prolonged but benign, and systemic PAN did not develop in any patient. The ulcerative form of disease was more prolonged and frequently associated with neuropathy. Therapy was varied, and the patients with non-ulcerative disease responded better than those with ulcers. Observations suggested that agents such as corticosteroids, azathioprine, pentoxifylline, and hydroxychloroquine were effective in individual patients.
This study highlights the associations that might occur in up to 40% of patients, the fact that neuropathy is relatively common, and that the course and response to treatment are dependent on the presence of ulceration.
Matsumara Y, Mizuno K, Okamoto H, Imamura S. Br J Dermatol 2000; 142: 561–2.
The authors report a case of cPAN in association with ulcerative colitis in a 69-year-old woman.
cPAN has been reported in conjunction with inflammatory bowel disease on numerous occasions. A careful focused history is the preferred method of evaluation. Radiologic or endoscopic studies are not generally necessary.
Kawakami T, Yamazaki M, Mizoguchi M, Soma Y. Arthritis Rheum 2007; 57: 1507–13.
In this study anti-phosphatidylserine–prothrombin complex and/or anti-cardiolipin antibodies were positive in all 16 cPAN patients tested compared to none in the control group.
Soufir N, Descamps V, Crickx B, Thibault V, Cosnes A, Bécherel PA, et al. Arch Dermatol 1999; 135: 1001–2.
These authors studied 16 patients with cPAN and found antibodies to hepatitis C in five. One patient was co-infected with HIV, and one had evidence of a prior hepatitis B infection.
Hepatitis C serology should be performed in patients with cPAN. Livedo reticularis with cryoglobulinemia can be seen with hepatitis C infection.
Kermani T, Ham E, Camilleri M, Warrington K. Semin Arthritis Rheum 2012; 42: 213–21.
This is a case series of nine patients with PAN-like vasculitis in the context of minocycline use. Four of the patients had isolated cutaneous disease. All patients had positive pANCA. Minocycline was discontinued and six patients required immunosuppressive therapy.
Vasculitic conditions mimicking cPAN have been reported with isotretinoin and amphetamines.
Jorizzo JL, White WL, Wise CM, Zanolli MD, Sherertz EF. J Am Acad Dermatol 1991; 24: 973–8.
These authors reported three patients with cPAN who responded dramatically to low-dose weekly methotrexate therapy.
Kawakami T, Soma Y. J Am Acad Dermatol 2011; 64: 1213–14.
This antimetabolite/immunosuppressive agent is not available in the US, but has been regularly used in Japan for PAN and cPAN.
Kluger N, Guillot B, Bessis D. J Dermatolog Treat 2011; 22: 175–7.
This is a single case report and combines a second-line and third-line therapy.
Marie I, Miranda S, Girszyn N, Soubrane JC, Vandhuick T, Levesque H. Intern Med J 2012; 42: 459–62.
This report describes three patients with refractory cPAN, resulting in painful ulcers involving the lower limbs and causing toe necrosis who were treated with IVIG 1 g/kg/day for 2 days monthly. After the second infusion, skin signs dramatically improved and completely healed after the third infusion.
Calderon MJ, Landa N, Aguirre A, Diaz-Perez JL. Br J Dermatol 1993; 12: 706–8.
A patient who failed to respond to aspirin and penicillin was treated with pentoxifylline. Withdrawal of the pentoxifylline resulted in a relapse that again responded to therapy.
Cvancara JL, Meffert JJ, Elston DM. J Am Acad Dermatol 1998; 39: 643–6.
Tamoxifen, an anti-estrogenic agent, at a dose of 10–20 mg daily, led to control of disease in a patient that seemed to worsen with conjugated estrogen therapy. Relapse occurred within 5 days of interruption of the therapy and rapidly responded with re-initiation of the tamoxifen.
Garcia-Porrua C, Gonzalez-Gay MA. Clin Exp Rheumatol 2003; 21: S138.
This is a report of an observation in a single patient.
Vega Gutierrez J, Rodriguez Prieto MA, Garcia Ruiz JM. J Eur Acad Dermatol Venereol 2007; 21: 570–1.
This is a single case report documenting efficacy of infliximab.
Misago N, Mochizuki Y, Sekiyama-Kodera H, Shirotani M, Suzuki K, Inokuchi A, et al. J Dermatol 2001; 28: 719–27.
In this report of four patients, two treated with tonsillectomy had resolution of their disease. The authors proposed that chronic streptococcal disease might be responsible for cPAN.
Kawakami T, Soma Y. J Am Acad Dermatol 2010; 63: 602–6.
This is a case series describing three patients with cPAN and anti-phosphatidylserine–prothrombin complex antibodies who experienced resolution of skin manifestations on sustained warfarin therapy.
Treatment of Skin Disease Comprehensive Therapeutic Strategies 4e
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Local measures, i.e., support stockings, local wound care
Non-steroidal anti-inflammatory drugs, penicillin (if antecedent streptococcal infection), systemic corticosteroids
Immunosuppressants: azathioprine, methotrexate, mycophenolate mofetil, mizoribine
Intravenous immunoglobulin
Pentoxifylline
Tamoxifen
Infliximab
Tonsillectomy
Warfarin
