Visceral disseminated varicella zoster virus infection after rituximab treatment for granulomatosis with polyangiitis

We report on a 30-year-old Japanese woman with granulomatosis with polyangiitis (GPA) complicated by pituitary diabetes insipidus and multiple lung granulomas. The granulomas disappeared with prednisolone (50 mg/day) and rituximab, although continuous nasal desmopressin was needed to control diabetes insipidus after immunosuppressive therapies. At the time of presentation, the patient had abdominal pain and disseminated intravascular coagulation but no rash. She died of continuous hemorrhage from her skin of neck, mucosa of her pharynx, and small intestine. At autopsy, varicella zoster virus (VZV)-DNA detected in serum and VZV antigens detected in tissues of her pharynx, esophagus, and liver led to a diagnosis of visceral disseminated VZV infection (VD-VZV). She also complicated cytomegalovirus infection in her stomach and ovaries. Her posterior pituitary gland had been replaced by foamy macrophages.

In 38 reported cases of VD-VZV, rash appeared following the onset of abdominal pain (mean interval, 6.5 days) but was lacking in 11% of cases. The mortality rate associated with VD-VZV was as high as 29% and survived cases were treated with antivirals earlier than mortal cases. A quick diagnosis with detection of VZV-DNA or VZV antigens in sera or tissues using PCR or immunohistochemistry examination and early empirical treatment with antivirals are important.     

Large-vessel involvement in granulomatosis with polyangiitis successfully treated with rituximab: A case report and literature review

Granulomatosis with polyangiitis (GPA) is primary necrotizing vasculitis, which predominantly affects small to medium vessels. Herein, we describe a case of a 60-year-old female with GPA who developed inflammatory wall thickening localized in the aortic arch, upper abdominal aorta, and pulmonary artery. The wall thickening in the large vessels and other GPA lesions such as lung nodules and orbital mass had failed to respond to high-dose glucocorticoids combined with cyclophosphamide; however, all were successfully treated with rituximab. Our literature review identified 24 cases of large-vessel involvement associated with GPA. Luminal stenosis, occlusion, or wall thickening were observed in 8, periaortitis in 11, and aneurysms in 5 cases. The most commonly affected vessel was the abdominal aorta (12 cases), followed by the thoracic aorta (6 cases), subclavian artery (4 cases), and internal carotid artery (4 cases). Glucocorticoids were used in 23 cases, 20 of which received combination therapy with cyclophosphamide. Surgical or endovascular therapies were performed in 10 cases with aneurysmal dilatation. This is the first case showing the potential efficacy of rituximab for refractory large-vessel involvement associated with GPA.     

Wegener's granulomatosis overlapped with Takayasu arteritis

Summary A 27-year-old woman presented with destructive scleritis of the left eye with subcutaneous haemorrhage and swelling of the lower eyelid. She had experienced recurrent nasal bleeding for the last six years, and chronic sinusitis resulting in the destruction of the nasal septum and left maxillary sinus. Nasal mucosal biopsies demonstrated granuloma formation with no evidence of vasculitis. The level of serum cytoplasmic anti-neutrophil cytoplasm antibody (c-ANCA) was significantly increased. Furthermore, multiple sites of complete occlusions were detected in the left subclavian and common carotid arteries by subtraction angiography and MRI. We describe a case of Wegener's granulomatosis overlapped with Takayasu arteritis, which, to our knowledge, has not been previously reported.     

Wegener's granulomatosis presenting as diabetes insipidus.

Pituitary gland involvement in Wegener's granulomatosis (WG) occurs most commonly in the form of central diabetes insipidus (CDI). However, CDI as a presenting manifestation of WG is very rare. We report two such cases; one of them had multi-organ involvement at presentation, while other developed it during follow-up. CDI was reversible following cytotoxic drug therapy in one of them.     

Relapsing Wegner's granulomatosis: Successful treatment with cyclosporin-A

Summary We describe the case of a 32-year-old splenectomised man with severe Wegener's granulomatosis which was refractory to conventional treatment with oral cyclophosphamide and prednisolone. Remission was temporarily induced only with plasma exchange or IV immunoglobulin. Because of frequent relapses of the disease and cyclophosphamide side effects, he was started on treatment with cyclosporin-A and a long lasting remission was achieved.     

Successful treatment of severe juvenile microscopic polyangiitis with rituximab

Microscopic polyangiitis (MPA) previously called hypersensitivity angiitis is a systemic necrotizing vasculitis affecting predominantly small vessels. MPA involves multiple organ systems including the lung, the kidneys, the joints, and the skin. MPA mostly affects adults in their fourth and fifth decade of life. MPA and Wegener`s granulomatosis are grouped together as ANCA-associated vasculitis. MPA is associated with high titre of myeloperoxidase antineutrophil cytoplasmic antibodies (MPO)-ANCA. We present a 14-year-old female patient presented with MPA. She was treated with steroids and cyclophosphamide. After the complication of severe lung involvement, rituximab was administered as immune-modulating treatment. The MPA came to remission. This is the first report of a pediatric patient with MPA treated with rituximab. Rituximab might be a potential therapeutic option for relapsing ANCA associated vasculitis in childhood.     

Successful treatment of mediastinal lymphomatoid granulomatosis with rituximab monotherapy

Lymphomatoid granulomatosis is a rare Epstein-Barr virus (EBV)-positive-B-cell lymphoproliferative disorder. Treatment options include corticosteroids, antiviral therapy, interferon-alpha and chemotherapy. However, long-term prognosis is poor and no therapeutic standard has been established yet. In a 21-year-old woman, a biopsy of mediastinal mass revealed lymphomatoid granulomatosis. Combined therapy with valganciclovir and interferon-alpha proved ineffective. In view of the CD20 expression of the tumor cells, monotherapy with rituximab was intiated. After 3 months a complete remission was achieved. Rituximab was continued for another 6 months with subsequent consolidation radiotherapy. This is the first report of an enduring complete remission (20 months) of a non-CNS lymphomatoid granulomatosis treated with rituximab.     

Rituximab as a new therapeutic option in granulomatosis with polyangiitis: a report of two cases

Abstract

Findings of several reports suggest that rituximab, a chimeric monoclonal anti-CD20 antibody causing B-lymphocyte depletion, might represent a treatment option for people with granulomatosis with polyangiitis (GPA) (former Wegener’s granulomatosis). This study presents the results of rituximab treatment in two patients with treatment-refractory GPA. First patient received rituximab for a granulomatous posterior orbital mass lesion, and eye symptoms were resolved after three courses of treatment. The second patient had eye and paranasal sinus involvement and benefited from two courses of rituximab treatment, with significant clinical improvement. Rituximab may represent an effective novel treatment for remission induction in GPA.     

Successful treatment with rituximab of refractory idiopathic thrombocytopenic purpura in a patient with Kabuki syndrome

Kabuki syndrome (KS) is often associated with autoimmune abnormalities, such as idiopathic thrombocytopenic purpura (ITP), autoimmune hemolytic anemia, leukoplakia and thyroiditis, as well as congenital anomalies. We herein present a KS patient with refractory ITP who achieved durable and complete remission in response to a total of four once-monthly infusions of rituximab. KS patients are often more susceptible to infection, so splenectomy should be avoided. Therefore, rituximab therapy is an alternative option for KS patients with ITP who fail to respond to first-line therapy.     

Erosive polyarthritis as presenting manifestation of Wegener's granulomatosis

Summary We describe a 55-year old female with an erosive symmetric polyarthritis and negative rheumatoid factor tests. A preliminary diagnosis was made of sero-negative rheumatoid arthritis. About two years after the first signs of arthritis, a diagnosis was made of Wegener's granulomatosis, based on bloody nasal discharge with active inflammation of the nasal mucosa with giant cells, the development of a saddle nose deformity, micro-haematuria and a strongly positive test for c-ANCA. After treatment with prednisone and cyclophosphamide the patient markedly improved. Wegener's granulomatosis has to be considered in a patient presenting with (erosive) (poly) arthritis.     

Successful treatment of isolated cutaneous relapse of follicular lymphoma with rituximab

Patients with follicular lymphoma (FL) usually present with advanced disease, with lymph nodes and bone marrow involvement. Extranodal infiltration is infrequent. In FL isolated cutaneous relapse is a very rare event that, to the best of our knowledge, has not been previously reported. We report on a 55-year-old woman with FL who presented with an isolated skin relapse 5 years after the diagnosis. The patient, who had relapsed after three lines of chemotherapy, was treated with the chimeric anti-CD20 antibody, rituximab, achieving a complete response, which has now persisted for more than 24 months.     

Successful rituximab treatment of refractory hemophagocytic lymphohistiocytosis and autoimmune hemolytic anemia associated with systemic lupus erythematosus

Abstract

High-dose steroids, immunosuppressants such as cyclophosphamide and cyclosporine, and high-dose intravenous immunoglobulin have all been used to control hemophagocytic lymphohistiocytosis (HLH) or autoimmune hemolytic anemia (AIHA) associated with systemic lupus erythematosus (SLE); however, some patients are refractory to treatment. Rituximab has successfully resolved many of the refractory manifestations of SLE. Here, we report a case of HLH and AIHA associated with SLE that was refractory or intolerable to conventional therapy, but was successfully treated with rituximab.     

An unusual presentation of eosinophilic granulomatosis with polyangiitis with a good response to rituximab

IntroductionEosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis that belongs to the anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides. It usually presents with late onset asthma in association with ear, nose and throat, cardiac, lung and gastrointestinal involvement.Aim of the workTo present a case of EGPA man with an unusual presentation.Case reportA 24 years old patient with EGPA presented with deep vein thrombosis and nerve palsy without a history of asthma or other usual manifestations of the disease. The left leg showed a skin rash and associated deep vein thrombosis as well as a small ulcer over the pulp of the right thumb. The total leucocyte count was 14.5 × 10⁹/L (41% eosinophils), erythrocyte sedimentation rate was 30 mm/1st hour and C-reactive protein 12.2 mg/L. Hepatitis B and C serology, antinuclear antibody (ANA) and antiphospholipid antibodies were all negative. ANCA was positive: myeloperoxidase (MPO) 36.9 U/ml and proteinase-3 (PR3) 15.9 U/ml and urinalysis was normal. The dermal and subcutaneous blood vessels displayed fibrinoid deposits, necrosis, and neutrophilic infiltrates in keeping with vasculitis. The patient showed a prompt and good response to corticosteroid and rituximab therapy with resolution of his symptoms.ConclusionThere is a necessity to keep an open eye for the diagnosis of EGPA in patients with eosinophilia even in the absence of asthma or other usual manifestations, as prompt therapy may be organ and life-saving. B cell therapy should be considered in patients resistant to conventional therapy and those in whom preservation of fertility is desired.     

Acute myeloid leukaemia presenting with diabetes insipidus

A 41‐year‐old man was diagnosed with hypogonadotropic hypogonadism managed with gonadotropins after routine fertility review. Eight months later he presented with new polydipsia and polyuria, lethargy and easy bruising. A full blood count showed 28% circulating blasts. A bone marrow biopsy confirmed a diagnosis of acute myeloid leukaemia with inv(3)(q21.3q26.2) with additional monosomy 7. Central diabetes insipidus (DI) was diagnosed following a water deprivation test. Pituitary magnetic resonance imaging showed a slightly thickened pituitary stalk, stable Rathke’s cyst, and new absence of the pituitary bright spot. The patient was commenced on desmopressin and induction chemotherapy, subsequently requiring a bone marrow transplant. Bone marrow examination at 100 days post‐transplant revealed cytogenetic remission. All symptoms of DI resolved and magnetic resonance imaging showed return of the posterior bright spot and a pituitary stalk of normal thickness. Biochemical hypogonadotropic hypogonadism persisted but was uninterpretable in the context of systemic illness and recent chemotherapy. DI is a rare complication of haematological malignancies, and the prevalence and pathophysiology of DI in this context are poorly understood. Pathogenic mechanisms proposed include leukaemic infiltration of the pituitary, interference with antidiuretic hormone synthesis, and abnormal thrombopoiesis influencing hormone levels. Particular cytogenetic abnormalities such as inv(3)(q21.3q26.2) and monosomy 7 appear to be more commonly associated with DI and also appear to confer worse outcomes. Aetiologies in the literature remain elusive but as DI is a recognised association of haematological malignancies it should be considered in a patient presenting with polydipsia and polyuria.     

Successful treatment and re-treatment of resistant B-cell chronic lymphocytic leukemia with the monoclonal anti-CD 20 antibody rituximab

We report on two patients with chemoresistant B-cell chronic lymphocytic leukemia who were treated successfully with the monoclonal anti-CD 20 antibody rituximab. Both patients suffered from severe thrombocytopenia requiring platelet transfusions over a period of several months. Neither chemotherapy nor immunosuppressive agents (corticoids, immunoglobulins) were effective. After four doses of rituximab (375 mg/m² weekly), both patients recovered within a few weeks to hematological partial remission. One patient was re-treated successfully three times after relapses. Both patients were premedicated with prednisone (100 mg) 30 min prior to the infusion to prevent cytokine release and the antibody infusions were well tolerated. Received: 5 May 1999 / Accepted: 18 October 1999     

Cyclophosphamide-associated enteritis presenting with severe protein-losing enteropathy in granulomatosis with polyangiitis: A case report

BACKGROUNDAlthough cyclophosphamide (CPA) is the key drug for the treatment of autoimmune diseases including vasculitides, it has some well-known adverse effects, such as myelosuppression, hemorrhagic cystitis, infertility, and infection. However, CPA-associated severe enteritis is a rare adverse effect, and only one case with a lethal clinical course has been reported. Therefore, the appropriate management of patients with CPA-associated severe enteritis is unclear.CASE SUMMARYWe present the case of a 61-year-old woman diagnosed with granulomatosis with polyangiitis based on the presence of symptoms in ear, lung, and, kidney with positive myeloperoxidase-antineutrophil cytoplasmic antibody. She received pulsed methylprednisolone followed by prednisolone 55 mg/d and intravenous CPA at a dose of 500 mg/mo. Ten days after the second course of intravenous CPA, she developed nausea, vomiting, and diarrhea, and was admitted to the hospital. Laboratory testing revealed hypoalbuminemia, suggesting protein-losing enteropathy. Computed tomography revealed wall thickening of the stomach, small intestine, and colon with contrast enhancement on the lumen side. Antibiotics and immunosuppressive therapy were not effective, and the patient’s enteritis did not improve for > 4 mo. Because her condition became seriously exhausted, corticosteroids were tapered and supportive therapies including intravenous hyperalimentation, replenishment of albumin and gamma globulin, plasma exchange, and infection control were continued. These supportive therapies improved her condition, and her enteritis gradually regressed. She was finally discharged 7 mo later.CONCLUSIONImmediate discontinuation of CPA and intensive supportive therapy are crucial for the survival of patients with CPA-associated severe enteritis.     

Recurrence of IgG4-related disease following treatment with rituximab

A 54-year-old woman with suspected low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type of the eyelids underwent rituximab-containing chemotherapy. She initially responded to the rituximab therapy, but later experienced two recurrences over a 3-year period. Biopsy specimens and a review of her previous histology revealed that she had had immunoglobulin G4-related disease at the initial presentation. Although IgG4-related disease seems to respond well to rituximab therapy, long-term follow up, including disease monitoring, is needed to evaluate disease remission.     

Low-dose rituximab in the treatment of acquired haemophilia

Objective and importance

Acquired haemophilia is a rare hemorrhagic disease caused by inhibitory autoantibodies against coagulation factor VIII. Rituximab has become a popular choice for immunosuppressive therapy in acquired haemophilia, almost with the same schedule of 375 mg/m² per week for 4–6 doses. While the effect of low-dose rituximab has seldom been reported.

Clinical presentation

We report a patient, aged 88 years, who developed acquired haemophilia with severe hemorrhage and elevation of carbohydrate antigen 125 (CA125), but in the absence of a detectable cause.

Intervention

We prescribed a low-dose rituximab alone (100 mg per week for a total of four infusions) for the patient, different from the conventional usage, but received a similar effect. In addition, the patient was diagnosed with immune thrombocytopenia 22 months after rituximab, while FVIII activity and activated partial thromboplastin time remained within the normal range. After four infusions of low-dose rituximab, the platelet count recovered.

Conclusion

At a follow-up of 34 months, the patient remains in remission without further treatment, suggesting low-dose rituximab seems to be a safe and effective regimen for the elderly patients with acquired haemophilia.