Microscopic polyangiitis M31.7

A rare, severe form of p-ANCA- or c-ANCA-positive (60% of patients) necrotizing, non-granulomatous (distinguished from granulomatosis with polyangiitis = Wegener’s granulomatosis)  "small vessel" vasculitis (microscopic) as a (minus) variant of "classic polyarteritis nodosa—cPAN," usually without involvement of medium-sized or large arteries.

Microscopic polyangiitis (MPA) is usually associated with necrotizing glomerulonephritis (70% of cases), pulmonary vasculitis, and allergic bronchial asthma. It is often difficult to distinguish diagnostically from granulomatous vasculitides: 

• Eosinophilic granulomatosis with polyangiitis(Churg-Strauss syndrome) 

and 

• Granulomatosis with polyangiitis/combinedwith sinonasal symptoms (= Wegener’s granulomatosis). 

The life-threatening pulmonary-renal clinical picture requires intensive care treatment in many cases.

The incidence is 0.6-0.8/100,000 per year.

See also: Granulomatosis with Polyangiitis(Wegener's Granulomatosis)

m>w; the majority of patients are over 50 years of age at the onset of the disease. Initial onset is also possible in childhood. See case report.   

Prodromal stage with adynamia, low-grade fever, night sweats, and weight loss. 50% of patients develop rheumatic symptoms (myalgia, arthralgia).

Kidneys: Renal involvement is possible as the disease progresses (80%) and may manifest as rapidly progressive glomerulonephritis.

Lungs: pulmonary capillaritis (25%), hemoptysis, pleurisy, and pneumonia.

Heart: Involvement of the cardiovascular system

Other: Involvement of the gastrointestinal tract and the peripheral nervous system (polyneuritis) is possible.

Skin (40%—the dermatologist is usually consulted only on a consultative basis for this clinical picture). Skin manifestations should be considered as monitoring symptoms. Only when evaluated in conjunction with internal symptoms (deterioration in general condition, fever, bloody nasal discharge, signs of glomerulonephritis, or pulmonary involvement) laboratory findings (detection of p-ANCA or MPO-ANCA), and histology (neutrophilic vasculitis of small vessels) can skin lesions associated with MPA be attributed to the underlying systemic disease:  

• disseminated, subcutaneous nodules and plaques (on the extremities but also on the face—see figure)
• palpable purpura(often the most prominent dermatological symptom)
• Livedo(persistent, compressible, reticular erythema) 
• Pyoderma gangrenosum-like(painful) ulcerations.

Positive (MPO-ANCA) p-ANCA in about 60% of pat. cANCAs may also be present in about 20% of patients.

High inflammatory parameters (ESR; CRP)

Note: pANCAs are not specific for MPA but are also found in other vaculitides.

A pronounced eosinophilia speaks against the disease.

Unremarkable epidermis; extensive filling of the dermis by dense, perivascularly concentrated infiltration of lymphocytic cells with numerous neutrophils and nuclear debris. Pronounced erythrocyte extravasation. Markedly swollen vascular endothelium and pronounced fibrin deposits within the vessel walls. Leukocytoclastic vasculitis without immune complex deposits.

Leukocytoclastic vasculitis: neutrophilic vasculitis of small vessels, no positive ANCA serology. 

Drug- and virus-induced exanthems: no positive ANCA serology; medical history and virologic findings are key. 

Pyoderma gangrenosum: clinical presentation, localized involvement, treatment-resistant (often locally recurrent) ulcer formation

Granulomatosis with polyangiitis (GPA)—histological evidence of granulomas

Eosinophilic granulomatosis with polyangiitis (EGPA)—eosinophilic granulomatous infiltrates are the key diagnostic feature

In larger cohorts with systemic vasculitides, the following distributions were observed: 66.7% with GPA, 17.0% with MPA, 16.3% with EGPA (Wójcik K et al. 2019). 

The treatment is identical to that for polyarteritis nodosa; see the entry there. Treatment should be conducted in collaboration with a specialized center. In cases of severe, life-threatening MPA, intensive care may be necessary! 

Severe, life-threatening MPA:

• Induction phase for new-onset or recurrent life-threatening MPA:
  • Prednisolone 50–75 mg/day, gradually tapered to a maintenance dose of 5 mg for up to 5 months (in very severe cases, pulse steroid therapy with 1–3 g may be indicated)plus
  • RTX ( ^{375 mg/m²}IV on days 1, 8, 15, 22; alternatively: 1,000 mg on days 1 and 15) or
  • CYC (0.6–0.75^g/m²) every 3–4 weeks for at least 6 months or
  • Cyclophosphamide —as an alternative to RTX in cases of severe renal insufficiency—usually as intravenous pulse therapy
  • Plasma exchange is necessary only in high-risk patients. 

For non-life-threatening or non-organ-threatening MPA (e.g., in combination with skin involvement without ulcerations):

• Treatment with prednisolone + RTX (alternatively, MTX or MMF)

5-year survival rate: approx. 70%; ANCA and CRP increases indicate a recurrence and a worsened prognosis.

The dermatological symptoms are extremely variable and not "'diagnosis-specific". Thus, the diagnosis can only be made by evaluating the histopathology in conjunction with the complex overall problem.

Kasuitik (Yamada Y et al. 2013): A 7-year-old girl was admitted to the pediatric ward due to severe anemia (hemoglobin 3.4 g/dl), fever, and cough. A chest X-ray (Figure 1A) and a computed tomography (CT) scan (Figure 1B) revealed diffuse infiltrates in both lung fields, which were more pronounced in the right lung, suggesting alveolar hemorrhage. Physical examination revealed maculopapular, erythematous, and purpuric lesions on the cheeks (Figure 2), elbows, and knees. Although a definitive diagnosis could not yet be made at that time, the patient was treated with a blood transfusion, antibiotics, and topical corticosteroids, which led to an improvement in symptoms and laboratory values within one week.

One month later, a similar rash recurred and was accompanied by pain in the knee joint, myalgia in the lower extremities, fever, cough, nasal discharge, and hemoptysis. Alveolar hemorrhage was suspected. Physical examination revealed skin lesions on the cheeks, elbows, and knees, similar to those observed at the time of the initial admission. In addition, palpable purpura was observed on the legs (Fig. 3) and on the dorsum of the foot.

Lab: White blood cell count 6,270/mm³ (normal range 3,500–8,500), neutrophils 69% (normal range 30–65), eosinophils 5% (normal range 0–6), monocytes 7% (normal range 4–12), lymphocytes 17% (normal range 20–55), atypical lymphocytes 2% (normal range < 0), red blood cell count 381 × 10⁴/mm³ (normal range 350–450 × 10⁴), hemoglobin 8.9 g/dl (normal range 11–16), platelets 31.6 × 10⁴/mm³ (normal range 12–40 × 10⁴), C-reactive protein 10.23 mg/dl (normal range 0–0.3), erythrocyte sedimentation rate 53 mm/first hour (normal range 20), aspartate aminotransferase 16 IU/l (normal range 8–40), alanine aminotransferase 7 IU/l (normal range 5–35), γ-glutamyltransferase 11 IU/l (normal range 9–79), alkaline phosphatase 269 IU/l (normal range 110–370), lactate dehydrogenase 244 IU/L (normal range 105–210), blood urea nitrogen 4 mg/dL (normal range 10–22), creatinine 0.22 mg/dL (normal range 0.4–1.1), total protein 6.6 g/dl (normal range 6.5–8.3), albumin 3.2 g/dl (normal range 3.8–5.1), KL6 352 U/ml (normal range 0–499.99), IgG 1279 mg/dl (normal range 932–1976), IgA 264 mg/dl (normal range 102–408 mg/dl), IgM 192 mg/dl (normal range 68–355), antinuclear antibodies < 40 (normal range < 40), anti-DNA antibodies < 2.0 IU/ml (normal range < 6.0), MPO-ANCA 34 EU (normal range < 20), proteinase 3 (PR3)-ANCA < 10 EU (normal range < 10), anti-glomerular basement membrane (GBM) antibodies < 10 EU (normal range < 10), and cryoglobulin negative (normal range negative). Proteinuria and microscopic hematuria were not detected. Although microscopic hematuria was detected, a renal biopsy revealed no abnormalities.

Histopathological examination of a skin biopsy taken from a purpuric papule revealed a normal epidermis and leukocytoclastic vasculitis of the small and medium-sized blood vessels with a neutrophilic infiltrate, leukocytoclasia, and extravasation of erythrocytes, affecting the entire dermis (Figure). Direct immunofluorescence tests were negative. Based on the clinical (palpable purpura and alveolar hemorrhage), histological (leukocytoclastic vasculitis of small and medium-sized blood vessels), and laboratory (positive for MPA-ANCA) findings, the patient was diagnosed with MPA associated with cutaneous manifestations and treated with methylprednisolone pulse therapy (30 mg/kg daily for 3 days), followed by oral prednisolone at a dose of 45 mg/day (2 mg/kg/day). Her symptoms, including the skin lesions, resolved within 2 weeks, and MPO-ANCA was no longer detectable. Histopathological examination of a kidney biopsy revealed no abnormalities. Prednisolone was tapered, and the patient was discharged on a prednisolone dose of 15 mg/day.

Course: During the subsequent 8-month follow-up period, the rash did not recur, and MPO-ANCA remained negative after the prednisolone dose had been reduced to a maintenance dose of 7.5 mg every other day. One year later, a new rash appeared, similar to that of the first and second episodes (cheeks, elbows, and knees; see fig.), accompanied by an increase in MPO-ANCA levels. Histopathological examination of a skin biopsy taken from an erythematous papule on the right knee revealed a subcorneal pustule containing neutrophils as well as focal spongiosis with multiple vesicles in the epidermis (Figure). Pronounced leukocytoclastic vasculitis was present throughout the dermis, affecting small and medium-sized blood vessels. In addition, massive interstitial infiltration of neutrophils and histiocytes, accompanied by nuclear dust, was evident in the collagen bundles. Direct immunofluorescence was negative. The prednisolone dose was increased to 15 mg/day, and mizoribin was added at a dose of 250 mg/day; this combination therapy led to an improvement in the skin lesions, with the exception of those on the knees, and MPO-ANCA was no longer detectable. The patient successfully continued treatment with 15 mg/day and mizoribine 100–250 mg/day without experiencing a clinical relapse. However, the skin lesions on the knees did not completely resolve and occasionally worsened with slightly elevated MPO-ANCA levels. Chest X-ray (A) and computed tomography (B) images revealed diffuse infiltrates in both lung fields, particularly in the right lung.

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