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. Women are more frequently affected than men (1.9:1).

Not confirmed; detection of immunoglobulins in the small arteries.

Evidence of association with hepatitis B/C infections. Also infections caused by parvovirus B19, as well as Mycobacterium tuberculosis and Chlamydia trachomatis. In children also streptococcal infections (streptococcal pharyngitis in particular).

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 subcutaneous nodules and plaques (90%): 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 (30-60%): 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 (10-20%) of the legs, especially the lower legs. Remark: The localized livedo racemosa is an important indicative phenomenon!

Livedo reticularis (40-90%): of the legs, especially the lower and upper thighs.

Petechial hemorrhages especially in the ankle area.

Atrophy blanche (25%): Pointed whitish scars.

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

Moderate increase in inflammatory parameters (ESR; CRP). Patients with ESR>20mm/h have a higher cumulative recurrence rate than patients <20mm/h.

Prothrombin antibodies; lupus anticoagulant; anti-cardiolipin antibodies), ANA titres, rheumatoid factor or cryoglobulins are generally negative (Munera-Campos et al. 2020).

Microscopic polyangiitis (classic form): severe p-ANCA-positive systemic disease.

Livedovasculopathy: no nodule formation, circumscribed livedo raceoma with painful, splatter-like ulcers

Erythema induratum Bazin : the extent to which identical clinical pictures are present here is currently unclear.

Erythema nodosum: acute recurrent painful nodules on the extensor sides of the lower legs

IgA vasculitis: purpura, vasculitis of small skin vessels, no nodular infiltrates; IgA immune complex disease

If hemolytic pharyngeal streptococci are detected, antibiotic therapy is necessary.

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

For more severe sympotmatics, glucocorticoids in medium doses are indicated, e.g. prednisolone (e.g. Decortin H) 40-60 mg/day.

In case of resistance to therapy, immunosuppressants such as azathioprine (e.g. Imurek) 100 mg/day, possibly in combination with low-dose glucocorticoids.

Alternatively: methotrexate (e.g. MTX) 7.5-15 mg/week or cyclophosphamide (e.g. Endoxan), DADPS (e.g. Dapson-Fatol) and sulfapyridine.

Alternative and in case of resistance to therapy: IVIG therapy

Alternative: etanercept or rituximab

Alternative: anticoagulant therapy with warfarin

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

Remember! Long-term monitoring of the patient, as transition to systemic polyarteritis nodosa is known in (few) individual cases.

Favorable. An eminently chronic, even relapsing course is typical. In around 50% of patients, only a single relapse is detectable, 50% tend to have a recurrent course of the disease.

Our own cases show a course that lasts for years, often accompanied by an elevated level of C-reactive protein and absolute neutrophil count (Munera-Campos M et al. 2020).

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.

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