Peripheral Neuropathy in ANCA Vasculitis

Antineutrophil cytoplasmic antibodies (ANCA)-associated diseases are necrotizing systemic vasculitides that affect small blood vessels (arterioles, capillaries and venules). This entity represents three main systemic vasculitides: granulomatosis with polyangiitis (GPA; formerly Wegener’s granulomatosis), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA; formerly known as Churg-Strauss’ syndrome). Their clinical manifestations are polymorphous, being the most frequent respiratory, oto-laryngo-pharyngeal and renal involvement. Peripheral neuropathy (PN) is reported in almost 50% of the patients. The aim of this chapter is to discuss the prevalence, clinical presentation, treatment and prognosis of PN in ANCA-associated vasculitis.

Eosinophilic granulomatosis with polyangiitis (Churg–Strauss syndrome) imitating Guillain–Barre syndrome (GBS): a case report

Background Eosinophilic granulomatosis with polyangiitis (EGPA) is associated with vasculitic neuropathy and being rare can present as subacute symmetric sensorimotor quadriparesis mimicking Guillain–Barre syndrome (GBS). It warrants timely diagnosis as treatment for both conditions is different and vasculitic neuropathy needs long-term immunosuppression. Nerve biopsy of our patient showed eosinophilic infiltration along with mononuclear infiltrate. Typical histopathological presentations of EGPA are different among different organs and eosinophilic infiltration is rarely observed in peripheral nerve and kidney involvements. Case presentation A 49-year-old female with a history of asthma with 3-week duration of acute onset ascending weakness, preceded by severe pain and burning in glove and stocking pattern. Nerve conduction studies could not rule out Guillain–Barre syndrome initially, but subsequent studies show axonal affection and she received intravenous immunoglobulin (IVIg) but her weakness progressed after slight improvement. Her bloodwork revealed marked eosinophilia (> 50%) with computed tomography (CT) paranasal sinuses showing pansinusitis with background history of asthma led us towards eosinophilic granulomatosis with polyangiitis and later antineutrophil cytoplasmic antibodies came out positive with nerve biopsy showing perivascular mononuclear inflammation with eosinophils. She was started on steroids immediately and then received intravenous rituximab in view of long-term immunosuppression with maintenance steroids and on follow-up she improved. Conclusion Eosinophilic granulomatosis with polyangiitis is a small-vessel vasculitis associated with antineutrophil cytoplasmic antibodies with significant paranasal sinuses involvement. Mononeuritis multiplex is the most common presentation of vasculitic neuropathy of eosinophilic granulomatosis with polyangiitis, but they can mimic Guillain–Barre syndrome and should always be considered in the differential diagnosis, since the treatment strategies for these conditions are radically different.

Immunological evaluation of patients with orthopedic infections: taking the Cierny–Mader classification to the next level

Introduction: Cierny–Mader osteomyelitis classification is used to label A, B, or C hosts based on comorbidities. This study's purpose was to define the “true” host status of patients with orthopedic infection using serologic markers to quantify the competence of their immune system while actively infected. Methods: Retrospective chart review identified patients at a single-surgeon practice who were diagnosed with orthopedic infection between September 2013 and March 2020 and had immunological laboratory results. All patients were A or B hosts who underwent surgery to eradicate infection. Medical history, physical examination, and Cierny–Mader classification were recorded. Laboratory results included complement total, C3, C4, immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin A (IgA), immunoglobulin E (IgE), rheumatoid factor, and antineutrophil cytoplasmic antibodies (ANCA) panel. Clinically significant results were defined as flagged abnormal. Normal complement levels and normal IgG levels were considered abnormal when infection was present. Results: Of 105 patients, 99 (94 %) had documented lab abnormalities. Clinically significant abnormalities were found in 33 of 34 (97 %) type-A hosts and 66 of 71 (93 %) type-B hosts. Eleven of 105 (10.5 %) patients were formally diagnosed with primary immunodeficiency by a hematologist. IgG deficiency, of either low or normal value, in the face of infection comprised 91 % (30 of 34) type-A hosts and 86 % (56 of 71) type-B hosts. Six (5.7 %) patients received IgG replacement therapy. Twenty-eight patients had abnormal total complement levels (low or normal): 7.4 % (2 of 34) A hosts and 40 % (26 of 71) B hosts (p=0.002). B hosts had statistically significantly lower complement levels and significantly more no-growth cultures (p<0.03). Thirteen of 14 patients with recurrent infections had low or normal IgG levels. IgM was significantly lower between reinfected patients and those without reinfection (p=0.0005). Conclusions: Adding immunologic evaluation to the Cierny–Mader classification more accurately determines patients' true host status and better quantifies risk and outcome with respect to orthopedic infection. Immunologically deficient A hosts should be quantified as B hosts. IgG deficiencies may be addressed when deemed appropriate by the consulting hematologist/immunologist. Patients with recurrent infections had significantly lower IgM levels than their nonrecurrent infection counterparts.

Facial nerve paresis in the course of masked mastoiditis as a revelator of GPA

Purpose The aim of this study was to present a series of 6 patients with facial nerve palsy and masked mastoiditis which constituted as revelators of localized granulomatosis with polyangiitis (GPA) and to evaluate the utility of the ACR/EULAR 2017 provisional classification criteria for GPA in such cases. Methods Study group included 58 patients with GPA. Cases with facial nerve palsy and masked mastoiditis were thoroughly analyzed. Results The mean age of patients was 37 years. All manifested unilateral facial nerve palsy and hearing loss, while only 2 reported aural complaints suggesting inflammatory cause of the disease. All cases were qualified for surgical intervention. Intraoperative findings were similar: granulation tissue in tympanic cavity and/or pneumatic spaces of the mastoid process. Only 50% of histopathological results suggested vasculitis. In all cases, elevated levels of antineutrophil cytoplasmic antibodies (ANCA) against peroxidase 3 (PR3-ANCA) were determined. Two patients presented rapid progression of the disease and died within 1 week and 2 months, respectively. Four other patients manifested gradual improvement of hearing and facial nerve function after treatment. Conclusion GPA should be included into differential diagnosis in all cases of persistent facial nerve palsy especially when otological symptoms coexist. Even localized GPA could be very aggressive, revelating generalized form of the disease. Rapid systemic treatment of GPA can protect hearing and facial nerve from permanent severe dysfunction. The ACR/EULAR 2017 provisional classification criteria for GPA seem to be valuable tool in diagnosing ENT patients with localized otological form of the disease.

Successful Rituximab Treatment in a Patient With ANCA-Negative Granulomatosis With Polyangitis: A Case Report

A 68-year-old woman was referred to our hospital for further evaluation of fever, nasal congestion, deafness, and multiple pulmonary nodules refractory to antibiotic use. Despite negative findings of antineutrophil cytoplasmic antibodies, she was diagnosed with granulomatosis with polyangiitis based on the analysis of biopsy specimens of pulmonary nodules. The administrations of oral prednisolone and six intravenous cyclophosphamide (IVCY) resulted in the prompt relief of symptoms and disappearance of pulmonary nodules. However, 3 months after the completion of IVCY therapy, nasal congestion and deafness flared up with an increase in the C-reactive protein level; a repeat computed tomography revealed a left lung nodule. Consequently, she underwent remission induction and maintenance therapy with rituximab (RTX), which resulted in the symptomatic improvement and disappearance of pulmonary nodule after 6 months. The patient remained in remission thereafter. Therefore, RTX may be an effective therapeutic option even in the absence of detectable autoantibodies.