Israel Medical Association Journal

Although the airway granulomata in Wegener's granulomatosis were stressed initially by Friedrich Wegener himself, in the last few decades systemic lesions mainly caused by acute vasculitis have received the most attention. However, recently, the implication of granulomatous manifestations in WG[1] has raised much interest. The present data suggest that an aberrant Th1-type response might play a role in the initiation of WG, clinico-pathologically characterized by granulomatous inflammation rather than vasculitis. Disease progression to generalized WG with the predominance of vasculitic manifestations is associated with a “switch” or further complexity of the collective T cell response with the appearance of another subset of Th2-type cells and a less prominent Th1-type cytokine production in the granulomatous lesions of the upper respiratory tract. However, the clinical significance of the granulomatous inflammation is not yet completely understood. Further research will also have to focus on the role of the granulomata during relapsing disease. We review present knowledge of granulomatous inflammation in WG. Morphologic aspects, the scale of cytokine alterations as well as the variety of clinical manifestations are discussed.

Objectives: To report our experience with three patients who developed autoimmune disease following prostatectomy.

Patients: Three patients presented with autoimmune phenomenon soon after a prostectomy for BPH[1] or prostatic carcinoma: one had clinically diagnosed temporal arteritis, one had leukocytoclastic vasculitis, and the third patient developed sensory Guillian-Barré syndrome following prostatectomy.

Conclusions: In view of the temporal association between the removal of the prostate gland and the autoimmune process, combined with previously known immunohistologic features of BPH, a cause-effect relationship probably exists.

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[1] BPH = benign prostatic hypertrophy

Background: Human parvovirus B19 is responsible for a variety of clinical syndromes, such as erythema infectiosum, non-immune hydrops fetalis, transient aplastic anemia, and arthropathies. HPV is also suspected of playing a role in the pathogenesis of various chronic inflammatory and autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, Kawasaki disease and multiple sclerosis.

Objectives: To study the age distribution and clinical presentation of patients hospitalized for human parvovirus B19 infection.

Method: We reviewed the case records of all pediatric patients with serologic evidence of HPV infection who were admitted during a 20 month period to a major community hospital

Results: Of 128 children tested for HPV, 48 had evidence of acute infection based on the presence of immunoglobulin M antibodies; 8 patients who also had positive IgM for other viruses were excluded, thus 40 case records were studied. The mean age of the patients was 5.21 years, but 22 patients were under 4: The clinical presentations included 25 patients with fever, either recurrent or prolonged, accompanied in some by enlarged spleen, liver and lymph nodes, skin rash and arthropathy; the remaining patients were investigated for anemia, skin rash, joint complaints and hepatitis. In addition; HPV infection was documented in several well-defihed clinical conditions, such as SLE, vasculitic skin lesions, acute lymphoblastic leukemia, pure red cell aplasia, and optic neuritis.

Conclusions: In a group of 40 pediatric patients exhibiting anti-HPV IgM antibodies, a younger age and less common clinical presentations were observed, furthermore 5 patients had clinical syndromes in which the causative role of HPV infection was not clear.

Anti-neutrophil cytoplasm antibodies are important markers of certain small vessel necrotizing vasculitides, but the optimal use of laboratory results in daily clinical practice necessitates collaboration between clinicians and laboratory specialists. Physicians must familiarize themselves with ANCA tests in ANCA-related vasculitides as well as in differential diagnostic patient populations in order to define cutoff values. Indirect immunofluorescence with a consensus-agreed technique combined with standardized enzyme immunoassays is the modality for detecting the main SSV-associated ANCA specificities using cutoff values that can sufficiently distinguish SVV from non-SVV patients. The combined use of IF and direct EIA to demonstrate proteinase 3-ANCA and myeloper­oxidase-ANCA at significant levels leads to a very high diagnostic specificity towards SVV conditions such as Wegen­er’s granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome, and limited forms of these such as renal-limited focal necrotizing glomerulonephritis. A strong reactivity of ANCA against several azurophil granule components indicates a drug-induced syndrome. ANCA-related SVV and drug­induced vasculitis or lupus syndromes have characteristic ANCA profiles that can help distinguish these conditions from other inflammatory diseases.

Objectives: To help clinicians and laboratory scientists recognize and utilize vasculitis-related ANCAs as an aid in diagnostic workup and patient follow-up, and be aware that ANCAs with different characteristics are commonly found in other chronic inflammatory conditions that persistently engage neutrophils in the inflammatory process.

Methods: Indirect immunofluorescence and enzyme immunoassay methods were used to detect ANCAs with both known and unknown neutrophil autoantigenic targets.

Results: Primary necrotizing small vessel vasculitides such as Wegener’s granulomatosis, Churg-Strauss syndrome, microscopic polyangiitis, and renal-limited rapidly progressive necrotizing glomerulonephritis target either the serine protease proteinase 3 or myeloperoxidase  in azurophilic granules. In ulcerative colitis and rheumatoid arthritis, we found multiple ANCA targets contained in azurophilic and specific granules, the cytosol and the nucleus, whereas PR3² and MPO³ were not, or only weakly, recognized.

Conclusions: ANCAs typically found in active SVV⁴ are demonstrable both by indirect immunofluorescence and antigen-specific enzyme immunoassay, and strong reactivity to either PR3 or MPO is characteristic. Strong ANCA with MPO reactivity is also found in some patients with drug-induced syndromes (lupus, vasculitis). Intermediate to strong perinuclear ANCAs are found in a substantial proportion of patients with UC⁵ (40–60%) and RA⁶ (30–70%), but in these conditions the ANCAs have many antigen targets that are only weakly recognized.

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¹ ANCA = anti-neutrophil cytoplasm antibody

² PR3 = protease proteinase 3

³ MPO = myeloperoxidase

⁴ SVV = small vessel vasculitides

⁵ UC = ulcerative colitis

⁶ RA = rheumatoid arthritis