Polyangiitis microscopic cutaneous M30.0

Lindberg 1931; Fisher and Orkin 1964

Rare, eminently chronic, relapsing progressive (monoorganic), dermal minus variant of systemic (ANCA-positive) polyarteritis nodosa with a disease pattern that affects the medium-sized arteries at the border between the dermis and subcutis. There is usually no systemic involvement as in the systemic form of polyarteritis nodosa.

w>m (in contrast to systemic PAN); cutaneous PAN is more common than classic systemic PAN but does not merge into it. However, the manifestations of ADA2 mutations show some overlapping similarities.

Not confirmed; detection of immunoglobulins in the small arteries. Frequent association with hepatitis B/C infections. Also infections caused by parvovirus B19 and Mycobacterium tuberculosis. In children also streptococcal infections.

Noteworthy is the occurrence of cutaneous polyarteritis nodosa after COVID vaccination/ChAdOx1 nCoV-19 (Su HA et al. 2022).

Drugs are also listed as a cause. Minocycline appears to play a special role here as part of acne therapy.

In a larger collective of cutaneous PAN patients (n=50), antiphospholipid antibodies were found in a high percentage (90%). This triggers endothelial activation with an inflammatory and procoagulatory vascular reaction.

The mean age of onset of the disease is 40-50 (with a wide range of 11-74) years (Kato A et al. 2018). Patients with ulcerated cutaneous PAN seem to be somewhat older.

Mainly located on the extensor sides of the lower extremities.

Painful nodules and plaques: often beginning with recurrent, 1.0 - 5.0 cm large, coarse, usually very pressure-dolent, also spontaneously painful, reddish to livid colored vasculitic plaques or nodules (iceberg phenomenon).

Painful ulcers (60%): due to the vasculitis with consecutive thrombosis of medium-sized vessels, painful ulcers develop (very painful ulcers may be the main clinical symptom). Healing of the ulcers with the formation of flat, sometimes hyperpigmented scars.

Livedo racemosa (90%) of the legs, especially the lower legs. Remark: The localized livedo racemosa is an important indicative phenomenon!

Petechial bleeding mainly in the ankle area.

Mild extracutaneous symptoms (detectable in 50%): Arthralgias (frequently in the ankle joints); myalgias or peripheral neuropathies (lower leg) are rarer.

No significant increase in inflammatory parameters (ESR; CRP). In larger collectives (Kawakami 2011), detection of antiphospholipid antibodies (70% anti-phosphatidyl prothrombin antibodies; 60% lupus anticoagulant; 20% anti-cardiolipin antibodies), relevant ANA titers, positive rheumatoid factor or cryoglobulins in 90% of kPAN cases.

• Polyangiitis microscopic (classic form): severe p-ANCA-positive systemic disease.
• Livedovasculopathy: no nodularity, described Livedo Raceoma with painful, splashy ulcers
• Erythema induratum Bazin : the extent to which identical disease patterns are present is not yet clear.
• Erythema nodosum: acute recurrent painful nodules on the extensor sides of the lower legs

Antibiotic therapy is necessary if hemolytic pharyngeal streptococci are detected.

Mild cases respond well to anti-inflammatories such as diclofenac (e.g. Voltaren Drg.) 50-150 mg/day p.o. or glucocorticoids such as prednisolone (e.g. Decortin H) in low dosage, initially 20 mg/day p.o., maintenance dose according to clinic.

In severe cases glucocorticoids in medium dosage, e.g. prednisolone (e.g. Decortin H) 40-60 mg/day. In therapy resistance, immunosuppressants such as azathioprine (e.g. Imurek) 100 mg/day, in combination with low-dose glucocorticoids if necessary.

Alternative: Methotrexate (e.g. MTX) 7.5-15 mg/week or cyclophosphamide (e.g. Endoxan), DADPS (e.g. dapsone-fatol) and sulfapyridine.

Alternative: IVIG therapy

Alternative: etanercept

Alternative: anticoagulant therapy with warfarin

Since the disease usually progresses over years, the medication should be carefully selected with regard to benefits/side effects.

Reminder. Long-term control of the patient, because in (few) individual cases transition to systemic polyarteritis nodosa is known.

Cheap. An eminently chronic, intermittent course is typical. Own cases show a course that lasts for years.

There is neither evidence nor proof that cutaneous polyarteritis nodosa can develop into systemic PAN.

Medical history: The multimorbid, 78-year-old obese patient reported recurrent painful nodules and plaques. These occurred for the first time after implantation of a hip joint prosthesis and healed spontaneously after 2-3 months. 5 years later recurrence of the skin changes lasting several months. 10 years later recurrence of painful nodules and plaques on both lower legs, which persist 2 years later. The patient suffers from permanent atrial fibrillation (I48.9) which is treated with direct oral anticoagulants (DOAK) and a pacemaker. She also has type 2 diabetes mellitus (E11.90) which is treated with oral antidiabetics.

Findings: On both lower legs painful red plaques and nodules of 2-3 cm in size are found. Next to them flat non-irritating scars and hyperpigmentation.

Histology: Inflammatory changes in arterioles and arteries in the subcutaneous tissue and at the border between cutis and subcutis. Here also described necroses and focal calcifications.

Laboratory: Inflammation parameters (BSG; CRP) in the normal range. Blood count: o.B. HbA1c: 6.1%; antiphospholipid antibodies +; ANA 1:80; Yersinia AK elevated with 66 U/ml; urine: nitrite++; bacteria+; leukocytes ++;

chest: o.B.; no indication of old or fresh tuberculosis.

Therapy: local treatment with a 0.1% triamcinolone ointment. No stem therapy was applied.

1. Akhter A et al (2015) Cutaneous manifestations of viral hepatitis. Curr Infect Dis Rep 17:452
2. Bauza A et al (2002) Cutaneous polyarteritis nodosa. Br J Dermatol 146: 694-699
3. Gushi A et al. (2000) Three cases of polyarteritis nodosa cutanea and a review of the literature. J Dermatol 27: 778-781
4. Jorizzo L et al. (1991) Low-dose weekly methotrexate for unusual neutrophilic vascular reactions: cutaneous polyarteritis nodosa and Behçet's disease. J Am Acad Dermatol 24: 973-978
5. Kato A et al. (2018) Clinical and Laboratory Markers Associated With Relapse in Cutaneous Polyarteritis Nodosa. JAMA Dermatol 154:922-926.
6. Kawakami T et al. (2011) Correlation of livedo racemosa, cutaneous inflammatory plaques, and antiphospholipid antibodies in patients with cutaneous polyarteritis nodosa. Medicine (Baltimore) 90:119-124.
7. Lindberg K (1931) A contribution to the knowledge of periarteritis nodosa. Acta Med Scand 76: 183-225
8. Mimouni D et al (2003) Cutaneous polyarteritis nodosa in patients presenting with atrophie blanche. Br J Dermatol 148: 789-794
9. Mondal R et al. (2014) Childhood Polyarteritis Nodosa: a prospective multicenter study from eastern India. Indian J Pediatr 81:371-374
10. Müller CSL et al. (2016) Diagnostic and histologic features of cutaneous vasculitides/vasculopathies. Act Dermatol 42: 286-301

11. Okazaki C et al. (2011) A case of cutaneous protothecosis in a polyarteritis nodosa patient and review of cases reported in Japan. Dermatol Online J 17:20

12. Pagnoux C et al. (2010) 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 62:616-626.

13. Papachristodoulou E et al. (2021) Therapeutic options for cutaneous polyarteritis nodosa: a systematic review. Rheumatology (Oxford) 60: 4039-4047.

14. Ratzinger G et al. (2015) The vasculitis wheel-an algorithmic approach to cutaneous vasculitis. JDDG 1092-1118
15. Schlitz M et al (1991) Periarteritis nodosa cutanea benigna-A frequently unrecognized disease. Act Dermatol 17: 162-165
16. Schneider SW (2016) Polyarteritis nodosa - a mystery? Close to the skin 32: 24-29

17. Su HA et al. (2022) Cutaneous polyarteritis nodosa following ChAdOx1 nCoV-19 vaccination. Int J Dermatol 61:630-631.

18. Sunderkötter C et al. (2015) Cutaneous symptoms of various vasculitides. Dermatologist 66: 589-598

19. Trueb RM et al (1995) Periarteritis nodosa cutanea. Dermatologist 46: 568-572
20. Zoshima T et ak. (2013) A case of refractory cutaneous polyarteritis nodosa in a patient with hepatitis B carrier status successfully treated with tumor necrosis factor alpha blockade. Mod Rheumatol 23:1029-1033