Evaluation of clinical benefit from treatment with mepolizumab for patients with eosinophilic granulomatosis with polyangiitis.

BACKGROUND: In a recent phase III trial (NCT02020889) 53% of mepolizumab-treated versus 19% of placebo-treated patients with eosinophilic granulomatosis with polyangiitis (EGPA) achieved protocol-defined remission. OBJECTIVE: We sought to investigate post hoc the clinical benefit of mepolizumab in patients with EGPA using a comprehensive definition of benefit encompassing remission, oral glucocorticoid (OGC) dose reduction, and EGPA relapses. METHODS: The randomized, placebo-controlled, double-blind, parallel-group trial recruited patients with relapsing/refractory EGPA receiving stable OGCs (prednisolone/prednisone, ≥7.5-50 mg/d) for 4 or more weeks. Patients received 300 mg of subcutaneous mepolizumab or placebo every 4 weeks for 52 weeks. Clinical benefit was defined post hoc as follows: remission at any time (2 definitions used), 50% or greater OGC dose reduction during weeks 48 to 52, or no EGPA relapses. The 2 remission definitions were Birmingham Vasculitis Activity Score of 0 plus OGC dose of 4 mg/d or less (remission 1/clinical benefit 1) or 7.5 mg/d or less (remission 2/clinical benefit 2). Clinical benefit was assessed in all patients and among subgroups with a baseline blood eosinophil count of less than 150 cells/µL, baseline OGC dosage of greater than 20 mg/d, or weight of greater than 85 kg. RESULTS: With mepolizumab versus placebo, 78% versus 32% of patients experienced clinical benefit 1, and 87% versus 53% of patients experienced clinical benefit 2 (both P < .001). Significantly more patients experienced clinical benefit 1 with mepolizumab versus placebo in the blood eosinophil count less than 150 cells/µL subgroup (72% vs 43%, P = .033) and weight greater than 85 kg subgroup (68% vs 23%, P = .005); in the OGC greater than 20 mg/d subgroup, results were not significant but favored mepolizumab (60% vs 36%, P = .395). CONCLUSION: When a comprehensive definition of clinical benefit was applied to data from a randomized controlled trial, 78% to 87% of patients with EGPA experienced benefit with mepolizumab.

Eosinophilic granulomatosis with polyangiitis in childhood: retrospective experience from a tertiary referral centre in the UK.

OBJECTIVE: To describe the presenting clinical features, treatment and outcome in children with eosinophilic granulomatosis with polyangiitis (EGPA) and to define factors that predicted mortality. METHODS: A retrospective case notes review of patients fulfilling the Chapel Hill Consensus Conference definition and/or ACR criteria for EGPA seen at Great Ormond Street Hospital, London. Demographics, clinical features, histopathology, treatment and outcomes were recorded. Descriptive statistics were expressed as median and range. Fisher's exact test was used for group comparisons. The Paediatric Vasculitis Activity Score and Paediatric Vasculitis Damage Index (PVDI) were calculated. RESULTS: Thirteen children (38% female) aged at diagnosis 14.1 (4-15.6) years were identified. The median time to diagnosis was 2 (0-7.3) years. History of asthma was documented in 76%. The most common presenting features were pulmonary (69%), skin (61%), gastrointestinal (46%), cardiac involvement (46%), paranasal sinus abnormality (38%), arthritis/arthralgia (38%) and neurological involvement (15%). Paediatric Vasculitis Activity Score at presentation was 8/63 (2-25/63); ANCA was negative in all 10/13 patients tested. Treatment included corticosteroids in all, combined with CYC in 38% or AZA in 23%. PVDI at 12 (3-48) months follow-up was 3/72 (0-13/72). Relapses were recorded in 46%. Mortality was 15%; cardiomyopathy and PVDI scores ⩾5 significantly associated with mortality risk (P = 0.012). CONCLUSION: EGPA in the paediatric population is a rare and potentially life-threatening vasculitis. Increased awareness is essential to secure a timely diagnosis and to promptly initiate treatment since our data emphasize a high mortality, particularly in those with cardiac involvement and significant accrued damage.

Intralesional Injection of Interferon-α2b in Orbital Eosinophilic Granuloma.

Considering the immune system dysfunction in unifocal orbital eosinophilic granuloma; possible complications of surgery, intralesional steroid, and radiotherapy; immunomodulatory and cytoreductive effects of interferon-α2b; and its safety profile in treatment of ocular surface neoplasia, intralesional interferon-α2b was first commenced in treatment of 3 cases (8-, 25-, and 43-year-old men) with biopsy proven orbital eosinophilic granuloma (2007-2014). Three intralesional injections of interferon-α2b (1.5 million units/0.5 ml) were given every other day. Cases 1 and 3 showed a rapid response with no recurrence in 86 and 29 months follow up. Case 2, however, required a second course of injection 2 months after the first one due to a partial response to the first injections with no recurrence at last follow up (57 months). Transient flulike symptom was the only side effect that was observed in Cases 2 and 3.

Canine eosinophilic granuloma of the digits treated with prednisolone and chlorambucil.

BACKGROUND: Canine eosinophilic granuloma (CEG) is an uncommon disease. Lesions are typically located in the oral cavity and other cutaneous sites, but are rarely reported to affect the digits. The majority of cases are treated with prednisolone as a monotherapy; alternative treatment options include corticosteroids administered in combination with azathioprine, antihistamines, electrochemotherapy with bleomycin, and surgical resection. Neither chlorambucil nor laser previously have been reported as treatments. OBJECTIVES: To describe an alternative therapy for treatment of CEG; using chlorambucil in combination with prednisolone for those cases that fail to respond to prednisolone alone. The new treatment was chosen according to good clinical practice and after owner consent. ANIMALS: Two client owned dogs. METHODS: One case was initially treated with carbon dioxide laser to debulk the lesions. Both cases were treated with a combination of oral prednisolone and chlorambucil. RESULTS: Both dogs experienced rapid resolution of lesions with prednisolone and chlorambucil therapy. Case 1 remained in remission three months after withdrawing medication. Case 2 experienced relapse 10 weeks after discontinuing therapy but was well controlled on maintenance prednisolone with chlorambucil at low, well tolerated doses. CONCLUSIONS AND CLINICAL IMPORTANCE: Although CEG appears to be an uncommon disease, it should be included as a differential diagnosis for dermal, nodular lesions affecting the digits. Chlorambucil appears to be an effective and well tolerated prednisolone sparing agent for treatment of CEG. Carbon dioxide laser ablation appears to be an effective method of debulking CEGs.

Pneumonia associated with Salmonella spp. infection in a cat receiving cyclosporine.

Salmonellosis is uncommon in cats, usually affects the gastrointestinal tract or skin, and can be fatal. This report describes a domestic shorthair cat with severe pneumonia caused by Salmonella spp. without accompanying gastrointestinal or skin manifestations, in which previous administration of cyclosporine may have played a permissive role in its development. Clinical and laboratory findings as well as follow-up are described from diagnosis until complete recovery. This unusual presentation serves to alert practitioners to consider Salmonella spp. as a possible cause of lung disease in cats, especially if immunocompromised.

[Surgical treatment combined with oral administration of indomethacin for eosinophilic granuloma of the skull: report of a pediatric case].

A 13-year-old girl presented headache for 5 d upon admission to hospital. An initial CT revealed 3 lesions located in her skull, the sizes of which were 2.5 cm×3.2 cm,1.2 cm×1.0 cm,0.3 cm×0.3 cm, respectively. The largest lesion was resected by surgery and confirmed as eosinophilic granuloma by pathology. After surgery, she took oral indomethacin 25 mg b·i·d for 3 months and tolerated it well. CT scan was performed 3 months and 1 year later, and the results showed that the unresected lesions shrank progressively and the defected bones were regenerated and healed one year later after operation.

Monosystem multifocal Langerhans cell histiocytosis (multifocal eosinophilic granulomas of the bone) in a 36-year old patient: case report, therapeutic doubts and review of literature.

Our aim is to provide review of available studies on Langerhans cell histiocytosis (LCH) and discuss treatment for polyostotic monosystem form of disease based on our clinical experience. LCH is an enigmatic disease with insufficiently understood etiology, pathophysiology, and variety of clinical presentations ranging from solitary eosinophilic granuloma to severe multisystem disease. It is marked by formation of granuloma in practically any organ. We present rare case of multifocal bone disease in 36-year old patient without visceral involvement. Treatment protocols for adult LCH patients, especially for uncommon form in our case have not yet been defined. Our therapeutical trial with corticosteroids showed limited success with numerous side-effects. We conclude that LCH treatment can commence only after diagnosis and staging of the disease. Other factors like patient's age, comorbidity, general condition, severity of symptoms and contraindications for therapy modalities should also be considered. In our experience expectative approach has better clinical outcome than immunosuppressive therapy in patients suffering from polyostotic multifocal form LCH with mild symptoms.

Solitary eosinophilic granuloma of the adult lumbar spine.

INTRODUCTION: Eosinophilic granuloma (EG) is a benign bone tumor that rarely occurs in adults. It is usually found occurring in flat and long bones, but spine is often affected too. EG is of unknown aetiology, and the course of the disease is unpredictable. MATERIALS AND METHODS: Two cases of EG of the adult lumbar spine are reported, representing a difficult challenge for diagnosis and treatment. CONCLUSION: CT scan guided trocar biopsy allowed to achieve a definitive diagnosis, and CT scan guided intralesional infiltrations of corticosteroids were the successful treatment.

Intralesional methylprednisolone for painful solitary eosinophilic granuloma of the appendicular skeleton in children.

BACKGROUND: Previous case reports and small series have reported on the treatment of eosinophilic granuloma of bone. We present our long experience in a large group of children and teenagers with symptomatic eosinophilic granuloma of the appendicular skeleton to evaluate clinical and imaging outcome after methylprednisolone injection. METHODS: Sixty-six patients with symptomatic solitary eosinophilic granuloma of the appendicular skeleton treated by incisional or percutaneous biopsy and methylprednisolone injection were retrospectively studied. There were 38 boys and 28 girls (mean age, 7.2 y). The mean follow-up was 10.7 years (median, 11.2 y; range, 3 to 15 y). All patients presented with symptomatic lesions including pain or tenderness and fever and had 1 intralesional injection of methylprednisolone acetate after biopsy: 52 patients had incisional biopsy and 14 patients had percutaneous computed tomography-guided biopsy. RESULTS: Complete resolution of symptoms was observed in 58 patients (92%) at 48 to 72 hours (50 patients) and in 7 days (8 patients) after the procedure. Complete imaging reconstitution of bone was observed in 60 patients (95.2%) at 1 to 2 years after the procedure. No patient had recurrence. Multifocal disease was diagnosed in 7 patients (11%) at 3 months to 6 years. Complications occurred in 2 patients: one patient with a clavicular lesion had a pathologic fracture after open direct methylprednisolone injection and the second patient developed trochanteric bursitis after computed tomography-guided methylprednisolone injection. CONCLUSIONS: Biopsy and direct intralesional methylprednisolone injection is safe for symptomatic eosinophilic granulomas of the appendicular skeleton in children with effective clinical and imaging resolution of the lesions.

Response of feline eosinophilic plaques and lip ulcers to amoxicillin trihydrate-clavulanate potassium therapy: a randomized, double-blind placebo-controlled prospective study.

In this study, we evaluated the treatment of feline eosinophilic plaques and lip ulcers with amoxicillin trihydrate-potassium clavulanate (Clavamox(®); Pfizer Animal Health). Nineteen cats with clinical and cytological findings consistent with eosinophilic plaques and/or lip ulcers were enrolled. Lesions were photographed and their areas measured in square centimetres before and after 21 days of therapy with either flavoured amoxicillin-clavulanate suspension or flavoured placebo suspension. Sixteen cats completed the study, with nine plaque lesions (four treatment and five placebo) and eight lip ulcer lesions (four treatment and four placebo) included in the analysis. All lesions were shown to have infection, with bacterial phagocytosis present on cytological examination. Coagulase-positive staphylococci were the most commonly isolated bacteria. The amoxicillin-clavulanate-treated eosinophilic plaque group had a statistically significant 96.2% reduction in mean lesion size (-7.60 cm(2), P = 0.0078) and an 80% reduction in mean percentage of microscopic fields demonstrating evidence of bacterial infection (P < 0.0001), whereas the placebo group did not. The amoxicillin-clavulanate-treated lip ulcer group had a 42.6% decrease in mean lesion size (-0.25 cm(2), P = 0.4125) and the placebo group a 36.6% increase (+0.49 cm(2), P = 0.1575), although neither change was statistically significant. The amoxicillin-clavulanate-treated lip ulcer group had a statistically significant 65.0% reduction in mean percentage of microscopic fields demonstrating evidence of bacterial infection (P < 0.0001), while no significant reduction was observed in the placebo group. A suspension of amoxicillin trihydrate-potassium clavulanate is an effective monotherapy for the treatment of feline eosinophilic plaques.

Oral eosinophilic ulcer, an Epstein-Barr virus-associated CD30+ lymphoproliferation?

Eosinophilic ulcer of the oral mucosa is a benign lesion of unclear pathogenesis mostly affecting the tongue. It has been suggested to represent a reactive pattern to several stimuli. We report on a 12-year-old boy who presented with a painless infiltrating ulcer on the gingiva of the lower jaw, which was covered by necrotic yellowish slough. There were no pathologic features of the jawbones or regional lymph nodes. Histopathological, immunohistochemical and gene rearrangement studies were in agreement with eosinophilic ulcer with predominant oligoclonal CD3+ and CD30+ T lymphocytes expressing the Epstein-Barr virus membrane protein. The ulcer resolved within 4 weeks and follow-up for 3 years revealed no evidence of recurrence. Epstein-Barr virus may have played a role in triggering this reactive lymphoproliferative disorder.

CT-guided corticosteroid injection for solitary eosinophilic granuloma of the spine.

OBJECTIVE: To evaluate the clinical and imaging outcome of patients with symptomatic eosinophilic granuloma of the spine treated with CT-guided intralesional methylprednisolone injection after biopsy. MATERIALS AND METHODS: Patients (n =19) with symptomatic solitary eosinophilic granuloma of the spine treated by CT-guided intralesional methylprednisolone injection were retrospectively studied. There were 12 males and seven females with a mean age of 17 years (range, 3-43 years). The mean follow-up was 6 years (median, 4 years; range, 0.5-19 years). Spinal location included the cervical (two patients), thoracic (seven patients), lumbar spine (eight patients), and the sacrum (two patients). Vertebra plana was observed in two patients. All patients had biopsies before treatment. RESULTS: Complete resolution of pain and healing of the lesion was observed in 17 patients (89.5%); none of these patients had recurrence at the latest examination. Reconstitution of the T1 and L1 vertebra plana was observed in both patients. Two patients initially diagnosed and treated for a solitary eosinophilic granuloma had constant pain after the procedure; in these patients, 6 and 12 months after the procedure, respectively, imaging showed multifocal disease and systemic therapy was administered. Complications related to the procedure were not observed. General anesthesia was administered in two patients because of intolerable pain during the procedure. CONCLUSIONS: In view of the benign clinical course of eosinophilic granuloma, in patients with symptomatic lesions, CT-guided intralesional corticosteroid injection is a safe and effective outpatient treatment with a low complication rate.

Clinicopathological Features, Risk Factors and Predispositions, and Response to Treatment of Eosinophilic Oral Disease in 24 Dogs (2000-2016).

The objectives of this study were to retrospectively describe clinicopathological features of eosinophilic oral disease in dogs, to identify possible risk factors or predispositions to the condition, and to report overall treatment response. Canine medical records from a veterinary teaching hospital and private referral practice over a 17-year period were reviewed for a diagnosis of eosinophilic oral disease. Twenty-four dogs with 26 lesions met the inclusion criteria. Patient mean age and body weight were 6.8 (3.8) years and 13.4 kg, respectively. Fifteen breeds were represented including Cavalier King Charles spaniel (16.7%), Labrador retriever (12.5%), and West Highland white terrier (12.5%). Eosinophilic lesions were found in the palate (65.4%), tongue (26.9%), and other oral locations (7.7%). Median follow-up time was 5 months. Analysis revealed statistically significant associations between lesion location and body weight (palatal and tongue lesions were more likely in smaller dogs, whereas lesions in the other category [lip or mucosa] were more likely in larger dogs). There was a correlation in lesion location and resolution (all dogs with palatal lesions became asymptomatic at their last recheck), and resolution and the use of antibiotics plus prednisone (greater likelihood of resolution without the use of this combination). Seventy percent of asymptomatic dogs resolved without medication or with allergen therapy alone, suggesting that asymptomatic dogs may respond well to conservative management. No associations were found between lesion location and breed, signalment and response to therapy, lesion resolution and the use of glucocorticoids, or significance of peripheral eosinophilia.

Myopericarditis as a presentation of eosinophilic granulomatosus with polyangiitis (EGPA).

A 60-year-old woman was admitted to the hospital with worsening dyspnoea, cough and chest pain. This was on a background of weight loss, decreased appetite, mononeuritis multiplex, chronic eosinophilia and a single episode of a non-blanching rash. Investigations demonstrated a raised troponin and ischaemic changes on ECG, and she was therefore initially treated for a presumed myocardial infarction. However, her symptoms failed to improve with treatment for the acute coronary syndrome. A coronary angiogram revealed no significant flow-limiting disease, and further investigations yielded confirmation of raised eosinophils and a positive perinuclear antineutrophil cytoplasmic antibody test. An echocardiogram demonstrated a pericardial effusion, and subsequent cardiac magnetic resonance features were compatible with myopericarditis. In light of these findings, the patient was diagnosed with eosinophilic granulomatous with polyangiitis and commenced on high-dose intravenous methylprednisolone and cyclophosphamide. She made an excellent recovery and remains in remission on azathioprine and a tapering dose of corticosteroids.

[Multifocal Langerhans cell histiocytosis of bone: late revelation in a 76-year-old woman]. / Histiocytose langerhansienne osseuse multifocale: révélation tardive chez une femme de 76 ans.

Langerhans cell histiocytosis or histiocytosis X has a variable course from a self-limited eosinophilic granuloma to an aggressive disseminated disease. It mainly affects children. We report a 76-year-old woman with multifocal bone histiocytosis X, involving the rachis, an iliac bone and the skull. The diagnosis has been established by histological exam. Outcome was favourable after chemotherapy.

[Orbital eosinophilic granuloma]. / Granuloma eosinofílico orbitário.

PURPOSE: To report the retrospective experience of a reference center in the diagnosis and treatment of orbital eosinophilic granuloma. METHODS: A review of the files in the Opththalmic Pathology Laboratory, of the Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, between 1974 and 2004, was conducted to identify cases of orbital eosinophilic granuloma. Data of diagnosis and treatment were collected. The hematoxilin and eosin stained sections were reviewed. RESULTS: Three cases with ages of 1, 6 and 11 years were retrieved. In none of them the clinical diagnosis of eosinophilic granuloma was suspected. All patients underwent diagnostic biopsy with characteristic histological aspect. In one case a orbital computed tomography after biopsy exhibited typical findings. All patients improved with systemic steroids./ CONCLUSIONS: This is a rare disease, with a difficult clinical diagnosis if radiological evaluation is not available. In spite of its aggressiveness at presentation, the disease shows good response to systemic steroids.

Eosinophilic granuloma of the skin: response to intralesional corticosteroid injection.

Langerhans cell histiocytosis (LCH) is a histiocytic disorder in which the Langerhans cell is arrested in a premature, partially active state. The disease comprises a spectrum of disorders, the most benign of which is a single-system unifocal disease. Lesions in single-system LCH are typically limited to the bone. We report a case of a 66-year-old man with a single-system disease limited to the skin, who was successfully treated with intralesional triamcinolone. This minimally invasive treatment method warrants further studies of intralesional corticosteroid injection for skin lesions of LCH.