A 73-year-old man, gardener by profession, with a previous chronic exposure to phos-phoric organs and pesticides, arrived in the department of Internal Medicine after access to the emergency room for intense asthenia, loss of appetite and weight loss of about 10 kg in two months. In the anamnesis, the patient did not report any particular pathologies, with the exception of nasal polyposis surgically treated about two months earlier. Diagnosis of first aid was: suspected intoxication with phosphoric esters. For sev-eral months the patient had constitutional symptoms, with fever and walking disorders with postural insta-bility and muscle pain in both lower limbs, associated with paraesthesia.

Blood tests showed increased indices of inflammation and anaemia. Blood tests performed in the emergency room showed iron deficiency anemia (Haemoglobin 7.5 mg/dl) reticulocytes 2.5%, mild renal impairment (creatinine 1.4 mg/dl) and increased inflammation indices (ESR 90 mm/h, RCP 18 mg/dL, D-dimers 4000). The patient was admitted to Internal Medicine to carry out the necessary investigations. During hospitalization, the patient presented fever; peak febrile blood culture and urine culture were normal. In the suspicion of an oncohaematological disease, specific blood chemistry tests were carried out: protein electrophoresis, serum and urinary immunofixation, tumor markers (CEA, CA 19.9, CA125, CA 15.3, alphafetoprotein, LDH, Jak2) were normal. Beta 2 microglobulin was slightly increased. Immunological lymphocyte subset typing was also performed showing activation of NK and CD8+ lymphocites.

An ultrasound of the abdomen was also performed to rule out splenomegaly; the examination did not show any abnormalities. In the suspicion of an oncological origin of the weight loss and inappetence, a total body  CT was also performed, which showed presence of bilateral pleural effusion and hydronephrosis in the right kidney, in the absence of suspected abdominal or chest injuries. Subsequently the dosage of the Free light k and lambda chains in serum and urine was carried out, resulting increased but with preserved ratio. At the same time, steroid therapy was administered with gradual improvement of the clinical conditions. In the absence of signs of infection or oncohaematological pathology and after resolution of the fever, the patient was discharged with low-dose corticosteroid therapy with an indication to suspend the therapy after one month, and an indication to repeat the blood tests after two months. After two weeks, however, the patient returned to the emergency room due to the reappearance of asthenia and fever and the worsening of his general clinical conditions. Blood tests showed a persistently increased ESR (125 mm/h), neutrophilic leuko-cytosis, hypereosinophilia, further increase in beta 2-microglobulin, worsening of renal function (serum cre-atinine 3.9 mg/dl), increased ferritin, anaemia (haemoglobin 7.8 mg/dl), and marked iron deficiency. A gas-troscopy was performed which highlighted hyperemic gastritis. During hospitalization, the patient com-plained of worsening paresthesia in the lower limbs and burning pain sensation; an electromyography was therefore performed which showed the presence of mononeuritis multiplex.

Therefore, in the suspicion of a systemic vasculitis complicated by neuropathy, specific blood chemistry tests were started, with the search for autoantibodies (p-ANCA, c-ANCA): positive p-ANCA (MPO) were in fact found. The presence of hypereosinophilia, the history of nasal polyposis and the finding of a mononeuritis multiplex on electromyography, in association with asthenia and steroid-responsive fever, indicated the pres-ence of a systemic vasculitis, therefore confirmed by the positivity of specific autoantibodies (p-ANCA). In consideration of the serious renal involvement demonstrated by the constant worsening of serum creati-nine levels and the reduction of the glomerular filtration rate, the patient also underwent a renal biopsy. Histological examination on the biopsy showed one in seven glomerulus in global sclerosis, diffuse ischemic phenomena, segmental area of fibrinoid necrosis of the flocculus in one glomerulus and diffuse interstitial infiltrate containing numerous plasma cells and eosinophilic infiltrate with severe tubulitis and glomerular capillaritis; diffuse endothelial swelling (Figures 1, 2, 3 and 4).

After biopsy therapy was carried out with high dose corticosteroids (intravenous methylprednisolone 500 mg for three days, therefore 1 mg/kg of body weight) and Cyclophosphamide 1000 mg one shot. After one week blood test showed a marked improvement in laboratory parameters, with a rapid decreasement of creatinine value, until normalization after four weeks. On discharge the patient was stable, afebrile, autono-mous in walkings and movements. Subsequent infusions of cyclophosphamide and periodic blood tests were scheduled, according to validated schemes for the treatment of ANCA-associated vasculitis [5,6].

After two months of therapy blood tests showed normal values of hemoglobin, sodium, potassium and in-flammation indices, decreased creatinine; mild lymphopenia. The patient is currently about to undergo the fourth infusion of cyclophosphamide on an outpatient basis at the internal medicine and immunology day service of our hospital, is clinically stable, is independent in walking, and he periodically performs rheumatological outpatient checks; he discontinued steroid ther-apy with no evidence of disease exacerbations.