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Cutaneous polyarteritis nodosa

Cutaneous polyarteritis nodosa
Literature review current through: Jan 2024.
This topic last updated: Mar 04, 2021.

INTRODUCTION — Cutaneous polyarteritis nodosa (cPAN) is a type of vasculitis affecting medium-sized vessels in the skin, a distinct subset of polyarteritis nodosa (PAN) first described in 1931 [1]. Whereas classic systemic PAN commonly affects the kidneys, joints, muscles, nerves, and gastrointestinal tract, as well as the skin, vasculitis in cPAN is skin-limited. (See "Clinical manifestations and diagnosis of polyarteritis nodosa in adults".)

Sometimes called "benign cutaneous PAN," cPAN can nevertheless result in significant morbidity due to painful skin nodules, digital infarcts, ulcerations, and other complications (picture 1A-E). Mild systemic symptoms, which must be distinguished from systemic vasculitis, may also develop.

The cutaneous manifestations of cPAN and systemic PAN are similar; therefore, all patients with cPAN should be evaluated for systemic involvement at the time of diagnosis. In addition, patients with cPAN should be monitored closely over time for progression to systemic PAN. Progression of cPAN to systemic PAN is rare but has been reported.

The clinical features, diagnosis, and treatment of cPAN will be reviewed here. Systemic PAN and the general approach to the diagnosis of vasculitis are reviewed separately. (See "Clinical manifestations and diagnosis of polyarteritis nodosa in adults" and "Treatment and prognosis of polyarteritis nodosa" and "Overview of and approach to the vasculitides in adults" and "Evaluation of adults with cutaneous lesions of vasculitis".)

EPIDEMIOLOGY — Polyarteritis nodosa (PAN) is itself a rare disease, with an estimated prevalence of roughly 31 cases per million [2]. cPAN is an even rarer subset of PAN for which the true prevalence is unknown [3]. cPAN may account for approximately 4 percent of PAN cases [4].

Systemic PAN is more common in men than women, but the reverse appears to be true of cPAN. A series of 79 patients revealed a female-to-male ratio of 1.7:1 [5], while two smaller series also found elevated rates of cPAN among women [6,7]. The disease most commonly presents in individuals in their 40s and 50s [5], though children also can be affected [8,9].

ETIOLOGY — The etiology and pathogenesis of polyarteritis nodosa (PAN) are unknown. Given the varied clinical manifestations of systemic and single-organ disease, "polyarteritis nodosa" may represent a spectrum of disease without a single pathophysiologic explanation. In some cases, immune complex deposition may be important. Deposition of C3 and immunoglobulin M (IgM) in vessel walls has been identified [10], as have IgM anti-phosphatidylserine-prothrombin complex antibodies, which may play a role in complement activation, vessel injury, and thrombosis [11]. How immune complex deposition leads to inflammation of medium-sized arteries but mostly spares the smaller vessels affected in other types of immune complex-mediated vasculitis is unclear; other pathophysiologic mechanisms likely play a role.

Mural inflammation of involved medium-sized arteries in PAN leads to luminal narrowing and thrombosis, as well as aneurysmal dilation and rupture. The resulting ischemia leads to downstream tissue damage and necrosis. In the case of the skin, manifestations such as tender subcutaneous nodules, retiform purpura, ulceration, and infarction result.

cPAN is most often idiopathic. An associated medical condition has been suggested in perhaps 40 percent of patients [5,6], including various infections, autoimmune diseases, and medications. Examples include Group A Streptococcus infection (most common) [5,12-17], hepatitis B virus infection [18-20], hepatitis C virus infection [21], recurrent urinary tract infection [5], parvovirus B19 infection [22], Mycobacterium tuberculosis infection [6,23], inflammatory bowel disease [5,24-26], and long-term exposure to minocycline [27-32].

Recessive loss-of-function mutations in CECR1, the gene encoding adenosine deaminase 2 (ADA2), a growth factor that is the major extracellular adenosine deaminase, have been linked to a PAN-like vasculitis with onset in childhood [33,34]. These findings suggest a genetic susceptibility in some patients with cPAN and may shed further light on the pathophysiology of the disease. (See "Vasculitis in children: Incidence and classification", section on 'Polyarteritis nodosa' and "Adenosine deaminase deficiency: Pathogenesis, clinical manifestations, and diagnosis".)

CLINICAL FEATURES — cPAN presents with skin findings indistinguishable from those seen in cases of systemic polyarteritis nodosa (PAN). These findings are generally indicative of medium vessel vasculitis and include tender subcutaneous nodules, livedo reticularis, retiform purpura, cutaneous ulceration, digital infarction, and necrosis (picture 1A-E).

The majority of patients with cPAN present with tender 0.5 to 2 cm subcutaneous nodules and livedo reticularis as initial manifestations, and approximately half develop cutaneous ulcerations [5,35]. Patchy, focal livedo reticularis in a "starburst" pattern is considered typical (picture 1A) [36]. cPAN most often affects the legs (97 percent of patients), followed by the arms (33 percent), and the trunk (8 percent) [5,36].

In addition to cutaneous findings, patients with cPAN are also frequently reported to develop extracutaneous manifestations such as fever (9 to 30 percent), arthralgias (9 to 69 percent), myalgias (27 to 31 percent), and peripheral neuropathy (22 to 32 percent) [3,5-7,11,36]. Such symptoms are typically mild and transient, in contrast to the more significant extracutaneous symptoms seen in systemic PAN. Some authors have suggested that muscle and nerve symptoms in cPAN are secondary to focal skin damage and should be localized to areas of skin lesions [7].

In all, more than 60 percent of patients with cPAN are reported to develop extracutaneous symptoms [6,7,36]. Their presence makes distinguishing between cutaneous and systemic PAN more difficult. Systemic PAN typically presents with systemic symptoms (eg, fatigue, weight loss, fever, arthralgias) and signs of multisystem involvement (table 1), such as hypertension, renal insufficiency, mononeuritis multiplex, and abdominal pain, as well as skin lesions (see "Clinical manifestations and diagnosis of polyarteritis nodosa in adults"). True cases of cPAN should exhibit neither visceral manifestations of vasculitis nor muscle or nerve symptoms separate from skin lesions.

HISTOPATHOLOGY — Characteristic histologic findings of cPAN include inflammation and destruction of medium-sized arteries near the junction of the dermis and subcutis (picture 2). A brisk inflammatory infiltrate composed primarily of neutrophils and lymphocytes and, in perhaps one-third of cases, eosinophils, infiltrates the vascular and perivascular tissue, obscuring the vessel border. Hyalinization of the vessel wall, with fibrinoid necrosis and narrowing, thrombosis, or obliteration of the vascular lumen, is seen. Disruption of the internal elastic lamina may be apparent on standard hematoxylin and eosin staining or highlighted with the help of an elastin stain. Surrounding smaller vessels, as well as nearby fat lobules, may be secondarily inflamed. In older lesions, fibrosis and neovascularization are seen, while inflammation may be less marked. It may be necessary to cut serial sections in order to identify the involved artery [5,14,36].

Direct immunofluorescence, if performed, may be positive for C3 and immunoglobulin M (IgM) in vessel walls, but these findings are variable and do not aid in distinguishing cPAN from systemic PAN or other vasculitides [10,11].

DIAGNOSIS — As with other types of vasculitis, careful clinicopathologic correlation is essential for the diagnosis of cPAN. In a patient with skin lesions suspicious for polyarteritis nodosa (PAN) (eg, subcutaneous nodules with livedo reticularis), a biopsy or biopsies should be performed and the results interpreted in the context of the clinical presentation. Once a diagnosis of medium vessel vasculitis is established in the skin, systemic organ involvement must be carefully ruled out. In addition, clinical and serologic clues should be sought to help confirm the specific type of vasculitis. (See "Evaluation of adults with cutaneous lesions of vasculitis".)

In sum, a diagnosis of cPAN can be made based upon the following:

Consistent cutaneous findings

Skin biopsy demonstrating vasculitis of medium-sized arteries

Exclusion of other types of vasculitis

Exclusion of systemic involvement

The importance of these features and a comprehensive assessment is reflected in proposed diagnostic criteria (table 2) [7].

History and physical examination — The clinical assessment of patients with suspected cPAN should include a thorough review of systems, medication history, and physical examination (including measurement of blood pressure).This assessment helps to exclude a diagnosis of systemic PAN and aids in the identification of triggers for cPAN, such as medication or inflammatory bowel disease. (See "Evaluation of adults with cutaneous lesions of vasculitis", section on 'Patient assessment' and 'Etiology' above.)

Skin biopsy — A skin biopsy of suspected PAN must be of adequate size and depth to sample medium-sized vessels in the deep dermis and subcutis [3]. This can be accomplished with an incisional biopsy, a deep punch biopsy, or a "telescoping" punch biopsy (also called the "double-trephine" technique) [37]. In a telescoping punch biopsy, a larger punch tool (eg, 6 mm diameter) is used to sample the epidermis and dermis, and a smaller punch (eg, 4 mm diameter) is used to acquire a deeper portion of subcutaneous fat within the resulting skin defect. Whichever technique is utilized, failure to submit a sufficient amount of subcutaneous tissue for review may lead to false negative results [3,37,38]. When nondiagnostic, skin biopsies may need to be repeated. (See 'Histopathology' above and "Skin biopsy techniques".)

Selection of the biopsy site is also important. In general, biopsy of a relatively "fresh" or new vasculitic lesion is most likely to show representative histologic changes. The biopsy should be centered over a tender nodule or purpuric lesion. If a PAN-associated ulcer is biopsied, ideally the central part of the ulcer should be sampled, along with the adjacent ulcer border and normal skin, taking care that an adequate amount of the subcutis is obtained [38].

A biopsy for direct immunofluorescence is unlikely to provide additional useful information and is therefore not routinely recommended in cases of suspected PAN. (See 'Histopathology' above.)

Laboratory tests — There is no specific serologic test that confirms a diagnosis of cPAN. However, patients in whom clinical and skin biopsy findings suggest PAN should have laboratory studies to assess for features suggestive of systemic involvement. The basic laboratory work-up includes:

Complete blood count

Basic metabolic panel

Liver function tests

Urinalysis with microscopic evaluation

Of note, mild anemia is fairly common in cPAN, affecting roughly 30 percent of patients. [5,36]. In addition, a normal urinalysis without hematuria or proteinuria does not rule out medium vessel vasculitis of the kidneys, which typically results in renovascular hypertension, not glomerulonephritis. Abnormalities in creatinine or liver function tests may suggest more significant involvement of renal or hepatic vessels with resulting end-organ damage.

The erythrocyte sedimentation rate (ESR) is the most frequent laboratory abnormality (elevated in 60 to 70 percent of patients with cPAN) [5,36]; however the value of this test in the setting of cPAN is unclear. Elevation of ESR or C-reactive protein (CRP) does not necessarily signify the presence of systemic disease, nor does a normal value rule it out.

Additional tests are recommended to evaluate for other types of vasculitis that can affect medium-sized vessels. The following studies are indicated for all patients:

Antinuclear antibodies

Antineutrophil cytoplasmic antibody (ANCA)

Rheumatoid factor (RF)

Serum cryoglobulins

Complement components (C3 and C4)

These studies are typically normal/negative in PAN but are helpful for evaluating for ANCA-associated vasculitis (ANCA), cryoglobulinemic vasculitis (RF, cryoglobulins, complement levels), and rheumatoid vasculitis (RF). (See 'Differential diagnosis' below and "Granulomatosis with polyangiitis and microscopic polyangiitis: Clinical manifestations and diagnosis" and "Overview of cryoglobulins and cryoglobulinemia" and "Clinical manifestations and diagnosis of rheumatoid vasculitis".)

In addition, a search for laboratory evidence of possible infectious triggers should be performed, including testing for hepatitis B and C virus infection, recent streptococcal infection, and tuberculosis [14]. In otherwise asymptomatic patients, our initial evaluation includes testing for hepatitis B surface antigen, hepatitis B core antibody, and hepatitis C antibody; an antistreptolysin-O titer; and either a tuberculin skin test or interferon gamma release assay. (See "Acute rheumatic fever: Clinical manifestations and diagnosis", section on 'Evidence of preceding GAS infection' and "Tuberculosis infection (latent tuberculosis) in adults: Approach to diagnosis (screening)".)

Additional tests for infection may be warranted based upon the patient history, clinical findings, and review of systems. (See 'Etiology' above.)

Other tests — Symptoms guide the need for further testing. Systemic PAN most often affects the kidneys, joints, muscles, nerves, and gastrointestinal tract. Additional evaluation may include nerve conduction studies (patients with paresthesias), muscle enzymes (patients with myalgias or muscle weakness), and stool guaiac testing (patients with abdominal pain), as dictated by the patient's specific symptoms [3,14].

Computed tomography (CT) or magnetic resonance imaging (MRI) angiography, or conventional mesenteric or renal angiography, may help identify visceral PAN and should be performed in patients with abdominal pain, hypertension, renal dysfunction, or other symptoms concerning for systemic PAN. The presence of aneurysmal dilation and narrowing of medium-sized vessels in the renal, mesenteric, or splenic circulation is characteristic of visceral disease. There are no data to support screening all patients with cPAN for systemic involvement with these advanced imaging modalities. (See "Clinical manifestations and diagnosis of polyarteritis nodosa in adults", section on 'Arteriography and cross-sectional imaging'.)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis for cPAN primarily consists of systemic polyarteritis nodosa (PAN), panniculitis, and other types of vasculitis:

Systemic PAN – The most important differential diagnosis for cPAN is systemic PAN, which may present identically in the skin but has a much less favorable prognosis due to the potential for renal, neurologic, gastrointestinal, cardiac, and other systemic manifestations. Because of the potential for misdiagnosis and for disease evolution, the evaluation for systemic disease should be careful and complete, and patients with presumed cPAN should be monitored over time. (See 'Diagnosis' above and 'Natural history' below and 'Follow-up' below and "Clinical manifestations and diagnosis of polyarteritis nodosa in adults".)

Panniculitis – The differential diagnosis for tender subcutaneous nodules predominately on the lower extremities also includes erythema nodosum and other types of panniculitis. Histologically, these diagnoses exhibit a primary septal or lobular panniculitis. In cPAN, any panniculitis is secondary to inflammation and destruction of nearby vessels. The presence of other clinical manifestations of medium vessel vasculitis, such as retiform purpura, ulceration, and livedo reticularis, favors cPAN. (See "Panniculitis: Recognition and diagnosis" and "Erythema nodosum".)

Erythema induratum (nodular vasculitis) is a type of panniculitis that also exhibits vasculitis. It is often associated with M. tuberculosis infection. The disorder presents with tender subcutaneous nodules, typically on the posterior lower legs. Ulceration may be present. Histologically, erythema induratum exhibits a mostly lobular granulomatous panniculitis with necrotizing vasculitis [39]. In contrast to the medium vessel involvement that occurs in cPAN, the vasculitis in erythema induratum usually involves venules. (See "Erythema induratum (nodular vasculitis)".)

Other vasculitides – Other types of vasculitis that can affect both small and medium-sized vessels include microscopic polyangiitis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, cryoglobulinemic vasculitis, and rheumatoid vasculitis. Cutaneous findings more typical of small vessel vasculitis (eg, palpable purpura) or characteristic systemic symptoms (eg, sinusitis) and laboratory findings (eg, antineutrophil cytoplasmic antibody [ANCA] or rheumatoid factor positivity) help differentiate these diseases. Additionally, an entity known as lymphocytic thrombophilic arteritis may mimic cPAN by presenting with hyperpigmented, reticulated macules, predominately on the extremities. Such cases demonstrate a lymphocyte-predominant vasculitis of medium-sized vessels and follow an indolent course. The precise nature of this entity and its relationship to cPAN remains controversial [40]. (See "Overview of and approach to the vasculitides in adults".)

NATURAL HISTORY — cPAN usually follows a chronic, relapsing and remitting course lasting several months to many years. Flares of tender nodules, ulcers, and other lesions may be painful and take many weeks or months to resolve. Cutaneous ulceration, increased C-reactive protein level, and elevated absolute neutrophil count, along with other inflammatory markers at the time of presentation, may predict an increased risk of relapse [41].

While systemic symptoms, such as arthralgias, fever, and malaise, are generally mild, complications such as ulceration or digital infarction and autoamputation can have a significant impact on quality of life. Secondary infections and treatment-related side effects can also be significant.

Patients initially diagnosed with cPAN have been reported to develop systemic complications such as renal, testicular, and cardiac polyarteritis nodosa (PAN) years after the initial diagnosis [18]. Some reports may be complicated by issues of case definition; accurately differentiating cPAN from systemic PAN can be difficult.

The incidence of progression to systemic PAN is unclear. Development of systemic disease has been reported to occur in up to 10 percent of patients based upon a study in which 2 of 20 patients with cPAN developed systemic medium vessel vasculitis 18 and 19 years, respectively, after their initial diagnosis [42]. However, other case series suggest progression from cutaneous to systemic disease is rare. In cohorts of 79 [5], 22 [7], and 22 [6] patients, respectively, with average follow-up ranging from three to seven years, no patients initially diagnosed with cPAN went on to develop visceral disease. Because of the uncertainty regarding risk for progression to systemic PAN, long-term follow-up is essential. (See 'Follow-up' below.)

TREATMENT — Because vasculitis in cPAN is skin-limited, therapeutic decisions should be tailored to the severity of the cutaneous manifestations and associated symptoms. Limited data are available to guide the management of cPAN. No prospective trial has been performed, and no specific regimen can be confidently recommended. The treatment suggestions provided here for various clinical presentations are based upon case reports, small case series, and expert opinion.

Mild disease — Mild cPAN manifesting primarily with subcutaneous nodules and livedo reticularis may improve with nonsteroidal anti-inflammatory drugs (NSAIDs), rest, and elevation of the affected limb(s) [3,15,26]. Agents with favorable risk profiles commonly used for skin-limited vasculitis, such as colchicine (0.6 mg twice daily) and dapsone (50 to 150 mg per day), are other reasonable choices for mild cPAN. In our experience, colchicine and dapsone yield greater improvement than NSAIDs. Therefore, we treat most patients with one of these agents. Colchicine and dapsone usually require several weeks of therapy before efficacy can be determined. An NSAID may be given concomitantly to aid in symptom relief.

Colchicine and dapsone are generally well tolerated. Dapsone can cause hemolytic anemia and should be avoided in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency because of risk for severe hemolytic anemia. Testing for G6PD deficiency should be performed prior to dapsone therapy. The adverse effects and monitoring recommendations for these drugs are reviewed separately. Refer to the Lexicomp drug information monographs for colchicine and dapsone included within UpToDate. (See "Colchicine: Drug information" and "Dapsone (systemic): Drug information".)

Topical therapy may be sufficient for superficial lesions (eg, local erythema), which may regress with potent topical corticosteroids (eg, clobetasol propionate) applied under occlusion twice daily over approximately four weeks [43].

Acute flares, ulceration, or extracutaneous symptoms — During acute flares of cPAN, particularly when associated with pain, ulceration, or extracutaneous symptoms such as arthralgias, myalgias, and paresthesias, systemic glucocorticoids are an appropriate initial therapy that tends to induce a satisfactory remission. Glucocorticoid-sparing agents are often added in an attempt to improve control and minimize the risk of glucocorticoid-induced side effects. (See "Major adverse effects of systemic glucocorticoids".)

Doses of prednisone of 30 mg per day or less may be sufficient for many adults [3,7,44-46]. However, higher doses (eg, 60 to 80 mg or 1 mg/kg of prednisone daily) should be given in the presence of more significant features such as severe ulceration or digital ischemia or when the response to lower doses is insufficient [5,8,14,15].

Once disease activity is controlled, the dose of glucocorticoids should be tapered slowly over a period of months, ranging from two to several depending on disease severity and the maximum dose required to achieve control. In some patients, the disease remits [36], but in others it flares with taper [5], and the adverse effects of chronic glucocorticoid therapy become dose-limiting. A glucocorticoid-sparing agent should be initiated if the disease flares with attempted glucocorticoid taper. Alternatively, one can be added at the time of initial therapy, especially for patients at high risk for glucocorticoid-related toxicities. Once remission has been achieved, the glucocorticoid taper can be resumed, and the glucocorticoid-sparing agent can be continued as long as it is tolerated and necessary to maintain disease control.

Nonimmunosuppressive glucocorticoid-sparing agents can be tried first unless disease manifestations are severe; benefit from colchicine, dapsone, sulfapyridine, hydroxychloroquine, and pentoxifylline has been described in case reports or case series [3,12,13,15,47]. Absent high-quality data to guide management, the choice of a particular glucocorticoid-sparing agent depends on several factors, including disease severity, clinician experience or comfort, and patient preference or comorbidities. Our initial choices for glucocorticoid-sparing therapy are typically colchicine (0.6 mg twice daily) or dapsone (50 to 150 mg per day), agents commonly used for other forms of cutaneous vasculitis. Patients who achieve only partial control or who remain glucocorticoid-dependent despite use of nonimmunosuppressive glucocorticoid-sparing agents may benefit from a switch to, or the addition of, an immunosuppressive glucocorticoid-sparing agent. (See 'Severe or refractory disease' below.)

cPAN associated with streptococcal infection — The role of antibiotic therapy for cPAN associated with streptococcal infection is unclear. Data from case series suggest that treatment or prophylaxis with penicillin may benefit patients with evidence of antecedent streptococcal infection or those whose symptoms seem to relapse or flare with recurrent infection [5,12,36,48]. We typically treat active streptococcal infections identified at the time of evaluation. Data are insufficient to recommend the routine use of prophylactic therapy.

Severe or refractory disease — In severe disease or cPAN refractory to systemic glucocorticoids, the addition of immunosuppressive agents to systemic therapy with glucocorticoids may be necessary. Azathioprine (0.5 to 2.5 mg/kg per day) or methotrexate (10 to 20 mg per week) are used frequently for these patients [5,12,44,49-52]. Some clinicians, including ourselves, check thiopurine methyltransferase (TPMT) enzyme activity prior to the initiation of azathioprine. Factors to consider regarding TPMT testing are reviewed separately. (See "Pharmacology and side effects of azathioprine when used in rheumatic diseases", section on 'Pharmacogenetics and azathioprine toxicity'.)

Patients whose disease course fails to improve with these agents may respond to cyclophosphamide, as would be more commonly used for systemic polyarteritis nodosa (PAN) [14,53]. The treatment of PAN with cyclophosphamide is reviewed in detail separately. (See "Treatment and prognosis of polyarteritis nodosa", section on 'Treatment of severe PAN'.)

The successful use of infliximab [54,55], etanercept [56], and intravenous immunoglobulin (IVIG) [47,57] has been described in case reports of a small number of patients. Such agents should be reserved for patients who are unresponsive to, or intolerant of, more commonly used drugs.

FOLLOW-UP — cPAN typically follows a chronic and relapsing course and has been reported to progress to systemic polyarteritis nodosa, albeit rarely. Because of the risk of progression, as well as the potential for initial misdiagnosis, careful follow-up is essential. A thorough review of systems and physical examination, blood pressure, and basic laboratory studies, including complete blood count and liver and renal function tests, should be performed regularly, at least every six months, even if the patient is otherwise asymptomatic [14].  

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Vasculitis".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

Basics topic (see "Patient education: Polyarteritis nodosa (The Basics)")

SUMMARY AND RECOMMENDATIONS

Cutaneous polyarteritis nodosa (cPAN) is a skin-limited vasculitis affecting medium-sized arteries. It closely resembles classic systemic polyarteritis nodosa (PAN) with respect to its cutaneous presentation but lacks the serious visceral complications of that disease. The diagnosis is most common in women in their 40s and 50s. (See 'Introduction' above and 'Epidemiology' above.)

Most cases of cPAN are idiopathic, but various infectious, autoimmune, and medication triggers have been described. The pathogenesis of the disease is poorly understood. Mural inflammation of medium-sized arteries leads to luminal narrowing and thrombosis, as well as aneurysmal dilation and rupture, with resulting downstream ischemic damage and necrosis. (See 'Etiology' above.)

Patients with cPAN typically present with 0.5 to 2 cm tender subcutaneous nodules and livedo reticularis (picture 1A-E). Approximately half develop cutaneous ulcerations. Retiform purpura, necrosis, and digital ischemia also occur. The legs are involved in nearly all cases, followed by the arms in one-third and, less commonly, the trunk. Patients may also develop mild systemic symptoms, including fever and arthralgias, as well as myalgias and peripheral neuropathy localized to areas of skin involvement. (See 'Clinical features' above.)

In a patient with skin lesions suspicious for cPAN, a biopsy or biopsies should be performed with adequate sampling of the deep dermis and subcutis, where medium-sized cutaneous vessels reside (picture 2). Biopsy findings should be interpreted in the context of the clinical presentation. No specific serologic test exists to aid in the diagnosis of cPAN. (See 'Histopathology' above and 'Diagnosis' above.)

The most important differential diagnosis of cPAN is systemic PAN, which may present identically in the skin but has a much less favorable prognosis due to the potential for renal, neurologic, gastrointestinal, cardiac, and other systemic manifestations. Because of the potential for misdiagnosis and, rarely, for disease evolution over time, evaluation for systemic disease should be careful and complete, and patients with presumed cPAN should be monitored over time. (See 'Differential diagnosis' above and 'Natural history' above and 'Follow-up' above.)

Limited data exist to guide the treatment of cPAN. Patients with mild cPAN manifesting as subcutaneous nodules and livedo reticularis can often be managed with nonsteroidal anti-inflammatory drugs and/or nonimmunosuppressive agents with activity in cutaneous vasculitis (eg, colchicine, dapsone). Rest and elevation of the affected limb(s) also may help to relieve symptoms. (See 'Treatment' above.)

For patients with acute disease flares, ulceration, or extracutaneous symptoms, we suggest systemic glucocorticoids as initial therapy (Grade 2C). Initiation of a glucocorticoid-sparing agent is indicated either at the time of initial therapy or if the disease flares upon tapering of the systemic glucocorticoid. (See 'Treatment' above.)

  1. Lindberg K. Ein Beitrax zur Kenntnis der Periarteritis nodosa. Acta Med Scand 1931; 76:183.
  2. Mahr A, Guillevin L, Poissonnet M, Aymé S. Prevalences of polyarteritis nodosa, microscopic polyangiitis, Wegener's granulomatosis, and Churg-Strauss syndrome in a French urban multiethnic population in 2000: a capture-recapture estimate. Arthritis Rheum 2004; 51:92.
  3. Morgan AJ, Schwartz RA. Cutaneous polyarteritis nodosa: a comprehensive review. Int J Dermatol 2010; 49:750.
  4. Pagnoux C, Seror R, Henegar C, et al. Clinical features and outcomes in 348 patients with polyarteritis nodosa: a systematic retrospective study of patients diagnosed between 1963 and 2005 and entered into the French Vasculitis Study Group Database. Arthritis Rheum 2010; 62:616.
  5. Daoud MS, Hutton KP, Gibson LE. Cutaneous periarteritis nodosa: a clinicopathological study of 79 cases. Br J Dermatol 1997; 136:706.
  6. Criado PR, Marques GF, Morita TC, de Carvalho JF. Epidemiological, clinical and laboratory profiles of cutaneous polyarteritis nodosa patients: Report of 22 cases and literature review. Autoimmun Rev 2016; 15:558.
  7. Nakamura T, Kanazawa N, Ikeda T, et al. Cutaneous polyarteritis nodosa: revisiting its definition and diagnostic criteria. Arch Dermatol Res 2009; 301:117.
  8. Merlin E, Mouy R, Pereira B, et al. Long-term outcome of children with pediatric-onset cutaneous and visceral polyarteritis nodosa. Joint Bone Spine 2015; 82:251.
  9. Bansal NK, Houghton KM. Cutaneous polyarteritis nodosa in childhood: a case report and review of the literature. Arthritis 2010; 2010:687547.
  10. Diaz-Perez JL, Schroeter AL, Winkelmann RK. Cutaneous periarteritis nodosa: immunofluorescence studies. Arch Dermatol 1980; 116:56.
  11. Kawakami T, Yamazaki M, Mizoguchi M, Soma Y. High titer of anti-phosphatidylserine-prothrombin complex antibodies in patients with cutaneous polyarteritis nodosa. Arthritis Rheum 2007; 57:1507.
  12. Fathalla BM, Miller L, Brady S, Schaller JG. Cutaneous polyarteritis nodosa in children. J Am Acad Dermatol 2005; 53:724.
  13. Assicot C, Bourrat E, Prigent F, et al. [Cutaneous polyarteritis nodosa in children: three cases]. Ann Dermatol Venereol 2002; 129:207.
  14. Bauzá A, España A, Idoate M. Cutaneous polyarteritis nodosa. Br J Dermatol 2002; 146:694.
  15. Choi SW, Lew S, Cho SD, et al. Cutaneous polyarteritis nodosa presented with digital gangrene: a case report. J Korean Med Sci 2006; 21:371.
  16. Stein RH, Phelps RG, Sapadin AN. Cutaneous polyarteritis nodosa after streptococcal necrotizing fasciitis. Mt Sinai J Med 2001; 68:336.
  17. Sheth AP, Olson JC, Esterly NB. Cutaneous polyarteritis nodosa of childhood. J Am Acad Dermatol 1994; 31:561.
  18. Minkowitz G, Smoller BR, McNutt NS. Benign cutaneous polyarteritis nodosa. Relationship to systemic polyarteritis nodosa and to hepatitis B infection. Arch Dermatol 1991; 127:1520.
  19. Van de Pette JE, Jarvis JM, Wilton JM, MacDonald DM. Cutaneous periarteritis nodosa. Hepatitis B surface antigen-containing immunocomplexes and polymorphonuclear-leukocyte lysosomal enzyme release. Arch Dermatol 1984; 120:109.
  20. Whittaker SJ, Dover JS, Greaves MW. Cutaneous polyarteritis nodosa associated with hepatitis B surface antigen. J Am Acad Dermatol 1986; 15:1142.
  21. Naouri M, Bacq Y, Machet MC, et al. [Interferon-alpha and ribavirin treatment in a patient with hepatitis C virus-associated cutaneous periarteritis nodosa]. Ann Dermatol Venereol 2006; 133:679.
  22. Durst R, Goldschmidt N, Ben Yehuda A. Parvovirus B19 infection associated with myelosuppression and cutaneous polyarteritis nodosa. Rheumatology (Oxford) 2002; 41:1210.
  23. Imanishi H, Tsuruta D, Oshimo T, et al. Cutaneous polyarteritis nodosa induced by Mycobacterium tuberculosis. J Dermatol 2012; 39:738.
  24. Magnant J, Lhommet C, Machet L, et al. [Cutaneous polyarteritis nodosa and Crohn's disease: An association not to be ignored]. Rev Med Interne 2009; 30:345.
  25. Komatsuda A, Kinoshita K, Togashi M, et al. Cutaneous polyarteritis nodosa in a patient with Crohn's disease. Mod Rheumatol 2008; 18:639.
  26. Tschetter AJ, Liu V, Wanat KA. Cutaneous polyarteritis nodosa presenting as a solitary blue toe. J Am Acad Dermatol 2014; 71:e95.
  27. Culver B, Itkin A, Pischel K. Case report and review of minocycline-induced cutaneous polyarteritis nodosa. Arthritis Rheum 2005; 53:468.
  28. Katada Y, Harada Y, Azuma N, et al. Minocycline-induced vasculitis fulfilling the criteria of polyarteritis nodosa. Mod Rheumatol 2006; 16:256.
  29. Schrodt BJ, Callen JP. Polyarteritis nodosa attributable to minocycline treatment for acne vulgaris. Pediatrics 1999; 103:503.
  30. Schaffer JV, Davidson DM, McNiff JM, Bolognia JL. Perinuclear antineutrophilic cytoplasmic antibody-positive cutaneous polyarteritis nodosa associated with minocycline therapy for acne vulgaris. J Am Acad Dermatol 2001; 44:198.
  31. Pelletier F, Puzenat E, Blanc D, et al. Minocycline-induced cutaneous polyarteritis nodosa with antineutrophil cytoplasmic antibodies. Eur J Dermatol 2003; 13:396.
  32. Odhav A, Odhav C, Dayal NA. Rare adverse effect of treatment with minocycline. Minocycline-induced cutaneous polyarteritis nodosa. JAMA Pediatr 2014; 168:287.
  33. Navon Elkan P, Pierce SB, Segel R, et al. Mutant adenosine deaminase 2 in a polyarteritis nodosa vasculopathy. N Engl J Med 2014; 370:921.
  34. Gonzalez Santiago TM, Zavialov A, Saarela J, et al. Dermatologic Features of ADA2 Deficiency in Cutaneous Polyarteritis Nodosa. JAMA Dermatol 2015; 151:1230.
  35. Munera-Campos M, Bielsa I, Martínez-Morillo M, et al. Manifestations, clinical course and prognostic markers in cutaneous polyarteritis nodosa. J Dtsch Dermatol Ges 2020; 18:1250.
  36. Diaz-Perez JL, Winkelmann RK. Cutaneous periarteritis nodosa. Arch Dermatol 1974; 110:407.
  37. Ha CT, Nousari HC. Surgical pearl: double-trephine punch biopsy technique for sampling subcutaneous tissue. J Am Acad Dermatol 2003; 48:609.
  38. Ricotti C, Kowalczyk JP, Ghersi M, Nousari CH. The diagnostic yield of histopathologic sampling techniques in PAN-associated cutaneous ulcers. Arch Dermatol 2007; 143:1334.
  39. Segura S, Pujol RM, Trindade F, Requena L. Vasculitis in erythema induratum of Bazin: a histopathologic study of 101 biopsy specimens from 86 patients. J Am Acad Dermatol 2008; 59:839.
  40. Vakili S, Zampella JG, Kwatra SG, et al. Lymphocytic Thrombophilic Arteritis: A Review. J Clin Rheumatol 2019; 25:147.
  41. Kato A, Hamada T, Miyake T, et al. Clinical and Laboratory Markers Associated With Relapse in Cutaneous Polyarteritis Nodosa. JAMA Dermatol 2018; 154:922.
  42. Chen KR. Cutaneous polyarteritis nodosa: a clinical and histopathological study of 20 cases. J Dermatol 1989; 16:429.
  43. Rogalski C, Sticherling M. Panarteritis cutanea benigna--an entity limited to the skin or cutaneous presentation of a systemic necrotizing vasculitis? Report of seven cases and review of the literature. Int J Dermatol 2007; 46:817.
  44. Flanagan N, Casey EB, Watson R, Barnes L. Cutaneous polyarteritis nodosa with seronegative arthritis. Rheumatology (Oxford) 1999; 38:1161.
  45. Borrie P. Cutaneous polyarteritis nodosa. Br J Dermatol 1972; 87:87.
  46. Khoo BP, Ng SK. Cutaneous polyarteritis nodosa: a case report and literature review. Ann Acad Med Singapore 1998; 27:868.
  47. Maillard H, Szczesniak S, Martin L, et al. [Cutaneous periarteritis nodosa: diagnostic and therapeutic aspects of 9 cases]. Ann Dermatol Venereol 1999; 126:125.
  48. Fink CW. The role of the streptococcus in poststreptococcal reactive arthritis and childhood polyarteritis nodosa. J Rheumatol Suppl 1991; 29:14.
  49. Boehm I, Bauer R. Low-dose methotrexate controls a severe form of polyarteritis nodosa. Arch Dermatol 2000; 136:167.
  50. Mimouni D, Ng PP, Rencic A, et al. Cutaneous polyarteritis nodosa in patients presenting with atrophie blanche. Br J Dermatol 2003; 148:789.
  51. Jorizzo JL, White WL, Wise CM, et al. Low-dose weekly methotrexate for unusual neutrophilic vascular reactions: cutaneous polyarteritis nodosa and Behçet's disease. J Am Acad Dermatol 1991; 24:973.
  52. Schartz NE, Alaoui S, Vignon-Pennamen MD, et al. Successful treatment in two cases of steroid-dependent cutaneous polyarteritis nodosa with low-dose methotrexate. Dermatology 2001; 203:336.
  53. Kawakami T, Okano T, Takeuchi S, et al. Complete resolution of refractory cutaneous arteritis by intravenous cyclophosphamide pulse therapy. Int J Dermatol 2015; 54:e323.
  54. Campanilho-Marques R, Ramos F, Canhão H, Fonseca JE. Remission induced by infliximab in a childhood polyarteritis nodosa refractory to conventional immunosuppression and rituximab. Joint Bone Spine 2014; 81:277.
  55. Vega Gutierrez J, Rodriguez Prieto MA, Garcia Ruiz JM. Successful treatment of childhood cutaneous polyarteritis nodosa with infliximab. J Eur Acad Dermatol Venereol 2007; 21:570.
  56. Valor L, Monteagudo I, de la Torre I, et al. Young male patient diagnosed with cutaneous polyarteritis nodosa successfully treated with etanercept. Mod Rheumatol 2014; 24:688.
  57. Lobo I, Ferreira M, Silva E, et al. Cutaneous polyarteritis nodosa treated with intravenous immunoglobulins. J Eur Acad Dermatol Venereol 2008; 22:880.
Topic 109628 Version 5.0

References

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