Ustekinumab associated thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is a rare disorder. Plasma exchange therapy has been shown to significantly reduce mortality in patients with TTP. Here, we report a case of TTP associated with ustekinumab therapy after a period of 2-3 years. Ustekinumab, a monoclonal antibody that inhibits interleukin 12 and interleukin 23, is one of the newer treatments for psoriasis. Although our patient experienced a prolonged course of TTP requiring 1 month of daily plasma exchange therapy, he recovered and remains in remission after 6 months.     

Severe pancytopenia associated with low-dose methotrexate therapy for rheumatoid arthritis

OBJECTIVE: To report the occurrence of severe pancytopenia associated with low-dose methotrexate (MTX) therapy for rheumatoid arthritis. CASE SUMMARY: Two patients developed severe pancytopenia after 10 days (cumulative dose 15 mg) and 23 months (cumulative dose 1030 mg), respectively, of low-dose MTX therapy for rheumatoid arthritis. Both patients had renal impairment. One died and the other recovered completely. DISCUSSION: Pancytopenia is a rare adverse effect of low-dose oral MTX therapy. The exact mechanism for development of pancytopenia is unknown, although it is likely that several factors play a role. The most important risk factor for MTX toxicity is impaired renal function. This adverse effect may occur at any time during MTX therapy. CONCLUSIONS: Severe pancytopenia associated with low-dose MTX therapy for rheumatoid arthritis is a potentially serious complication that may occur at any time during therapy. This adverse effect is more likely to occur in patients with renal impairment.     

Infection as a cause of early relapse in patients recovering from thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is a rare but severe disorder characterized by hemolytic anemia, thrombocytopenia, fever, renal failure, and neurologic manifestations. Plasma exchange is the most effective treatment for this condition reducing mortality from 90% in untreated patients to 10%. However, infections acquired during the course of therapy could lead to early relapse of TTP. In this case report, we report three patients with TTP who initially responded well to plasma exchange treatments but suffered early relapses following bacterial infections. All these patients achieved remission once appropriate antibiotic therapy was instituted although one patient eventually received four courses of rituximab. This report emphasizes the need to be vigilant for new infections especially urinary tract infections in TTP patients undergoing plasma exchange. Instituting appropriate antibiotic therapy once an infection is suspected may reduce the need for prolonged plasma exchange procedures and extended hospital stay.     

Unilateral serous retinal detachment in a patient with thrombotic thrombocytopenic purpura

Ocular complications are a relatively common occurrence in patients with thrombotic thrombocytopenic purpura (TTP). Serous retinal detachment is a rare but reported complication, with most cases being bilateral and associated with concomitant hypertension. Therapeutic plasma exchange has been used to successfully treat patients with TTP. We report a case of a 46 year old woman who presented with TTP, received therapeutic plasma exchange, and developed unilateral serous retinal detachment with retinal pigment epithelial tear in the absence of reported hypertension. The increased perfusion pressure due to hypertension, combined with the choroidal vasculature damage from TTP are thought to lead to retinal epithelial tear. This suggests that although hypertension may play a role in retinal detachment in these patients, other mechanisms may be responsible.     

Therapeutic plasma exchange for hyperviscosity syndrome secondary to high rheumatoid factor

Hyperviscosity syndrome (HVS) is most commonly associated with Waldenstrom’s macroglobulinemia, where it may be life-threatening. HVS may also occur in autoimmune diseases; data pertaining to efficacy of therapeutic plasma exchange (TPE) in HVS arising in non-malignant gammopathy are limited. We report a case of 71-year-old female with erosive rheumatoid arthritis with profoundly elevated rheumatoid factor (57,400 IU/ml; normal <35) who presented with findings consistent with HVS: profound weakness, headache, epistaxis and plasma viscosity (8.5 centipoise). She was successfully treated with pulsed high-dose steroids and TPE. Her symptoms of HVS have not recurred and the plasma viscosity has remained less than 3 centipoise. Given a slow onset of non-specific symptoms, HVS may be missed, incurring high risk of adverse effect. In symptomatic patients with high RF activity, a high index of suspicion for HVS is necessary to ensure timely identification and treatment with TPE, a safe and effective therapy.     

Successful repeat therapy with rituximab for relapsed thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease that is treated successfully with therapeutic plasma exchange (TPE) and often with corticosteroids; however, almost one third of TTP patients have treatment failures that require either long-term TPEs or other adjunct therapies. Recent insights into the autoimmune-pathophysiology of this disease provide the rationale for immune-based therapies. Cumulative evidence suggests that rituximab, an anti-CD20 antibody that depletes B-cells temporarily, is an effective therapy in patients with refractory or relapsing TTP. We report here two patients with chronic relapsing TTP who were treated successfully with rituximab. However, both experienced TTP relapse following sustained and prolonged remissions for 21 and 37 months, respectively. They responded favorably with repeat therapy with rituximab. The benefits of rituximab treatment for refractory or relapsing TTP as well as in the prevention of recurrences are discussed.     

Efficacy of eculizumab in severe ADAMTS13-deficient thrombotic thrombocytopenic purpura (TTP) refractory to standard therapies

Thrombotic thrombocytopenic purpura (TTP) is a rare microangiopathic hemolytic anemia (MAHA) defined by mechanical hemolytic anemia, severe thrombocytopenia, and systemic visceral ischemia due to systemic platelet-rich microthrombi. Forty percent of patients with autoimmune TTP experience one or multiple relapses. Patients with refractory TTP are currently managed by corticosteroids, twice-daily PEX, and the anti-CD20 monoclonal antibody rituximab. Herein, we report two cases of severe TTP, refractory to those standard agents. On the basis of the fact that in cases of severe TTP the classical complement pathway is activated, and that the alternative pathway is also involved, both patients underwent eculizumab (anti-C5 monoclonal antibody) therapy. We observed prompt hematological and organ system responses to the eculizumab and the recovery of plasma ADAMTS-13 activity in both cases. Moreover, the fact that both patients discontinued eculizumab, maintaining the response, emphasizes the possibility of its usefulness for limited treatment periods. In conclusion, the diagnostic and therapeutic algorithm in TTP appears complicated by increasing evidence of complement involvement and the eculizumab seems to be a potential agent for refractory patients.     

The Moschkowitz syndrome in emergency department. Case report

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening multisystem disorder of unknown etiology, first described by Moschkowitz in 1924. TTP is a thrombotic microangiopathy characterized by microvascular lesions with platelet aggregation. TTP is more common in adults and is associated with pregnancy; diseases such as HIV, cancer, bacterial infection, and vasculitis; bone marrow transplantation; and drugs TTP is a hematologic emergency. It is a multisystem disease that can cause rapid deterioration of the patient's neurologic, renal, and hematologic status. TTP is an uncommon disease with a high fatality rate if untreated or misdiagnosed. Rapid diagnosis and aggressive treatment by therapeutic plasma exchange are necessary to reduce the risk of a fatal outcome. Current clinical criteria for initiating therapy are: thrombocytopenia, and absence of other disease entities that could explain the thrombocytopenia. Early recognition and management are essential for patient survival. TTP is difficult to diagnose because the patient's presentation can be nonspecific and the characteristic pentad of symptoms may not occur together. Other disease entities can have some of the same symptoms. We discuss a case report of Moschkowitz syndrome in Emergency Department.     

Tocilizumab: A novel humanized anti-interleukin 6 (IL-6) receptor antibody for the treatment of patients with non-RA systemic,inflammatory rheumatic diseases

Abstract

Tocilizumab is a highly effective therapeutic agent for the treatment of rheumatoid arthritis and systemic juvenile idiopathic arthritis. Furthermore, a large amount of case study data reveals that tocilizumab can be an effective therapy for not only rheumatoid arthritis but also for other mostly rare inflammatory rheumatic diseases. By blocking the interleukin-6 pathway tocilizumab can be a useful therapeutic alternative when conventional treatment fails. It is successful in treating diseases such as the adult-onset Still's disease, amyloidosis, giant cell arteritis, multiple myeloma, polymyalgia rheumatica, relapsing polychondritis, remitting seronegative symmetrical synovitis with pitting edema-syndrome, systemic lupus erythematosus, systemic sclerosis, and Takayasu arteritis. Studies underway are now recruiting patients to acquire further data on treating patients with non-rheumatic arthritis, inflammatory diseases. This review focuses on tocilizumab as a promising agent for treating rare and orphan diseases in rheumatology for which no satisfactory treatment is yet available.     

Thrombotic thrombocytopenic purpura and pregnancy: report of four cases and literature review

Thrombotic thrombocytopenic purpura (TTP) is a severe life-threatening hematological disorder affecting the microcirculation of multiple organ systems. Infection, pregnancy, cancer, drugs, and surgery are frequently associated with the initial episodes and relapses. Women who are either pregnant or in the postpartum period make up 10-25% of TTP patients, suggesting the interrelationship between TTP and pregnancy. The introduction of aggressive treatment with plasma transfusion and plasmapheresis has improved maternal and fetal survival rates. We report four cases of pregnancy-related TTP, describing the clinical course of patients, including response to therapy and pregnancy outcomes. Three out of four (75%) patients were treated by daily single session of plasmapheresis for a period ranged between 3 and 23 days. One patient had complete response to treatment with no sequelae, the second patient had resistant disease and died due to multiorgan failure, while the third patient had complete response after 2 episodes of TTP, which was complicated by intrauterine fetal growth retardation and death. Review of the previously reported cases of pregnancy-related TTP and the current treatment options for this rare condition are discussed also.     

A case off TTP temporally associated with cocaine use: Implications for treatment of suspected DITMA

Thrombotic microangiopathies are rare diseases associated with significant morbidity and mortality. The treatment of thrombotic thrombocytopenic purpura (TTP) and drug-induced thrombotic microangiopathy (DITMA) remains a diagnostic dilemma as they present similarly but respond differently to standard treatment with plasma exchange. TTP is a deficiency of a disintegrin and metalloprotease with thrombospondin type 1 motif 13 resulting in von Willebrand factor aggregates. DITMA is due to vascular and platelet toxicity. Our case contradicts a notion in current literature that suggests supportive therapy when there is high suspicion for DITMA. We present what appears to be the second published case of cocaine temporally associated with TTP. Our case responded to therapy. We propose this case should influence weighing the risks and benefits of treatment of suspected DITMA and reinforces current official guidelines that suggest treating cases of suspected DITMA as TTP until the diagnosis is confirmed.     

Chronopharmacological and pharmacokinetic evaluation of the therapeutic effect of naproxen in rheumatoid arthritis

Patients with exacerbation of rheumatoid arthritis without antiinflammatory therapy demonstrated no regular circadian variations in clinical-laboratory indices of disease activity. A study of the therapeutic effect of 3 schemes with naproxen has shown that one should consider the time of development of maximum arthralgia in each individual patient and administer the drug 1 hour before it at quite a large single dose. The drug concentration in the blood plasma of the rheumatoid arthritis patients corresponded, on an average, to an administered dose showing no parallelism with a clinical effect of the drug.     

Treatment of plasmapheresis refractory thrombotic thrombocytopenic purpura with double-filtration membrane plasmapheresis

Thrombotic thrombocytic purpura (TTP) is a life-threatening disorder. Without plasma exchange treatment (PET) the mortality rate is quite high. Double-filtration plasmapheresis is an alternative opportunity for TTP patients refractory to PET. Here we report our experience in a refractory TTP patient who was successfully treated by means of double-filtration plasmapheresis therapy.     

Gene transfer to treat rheumatoid arthritis

Intraarticular transfer of exogenous genes could be useful for treatment of rheumatoid arthritis. The joints are not easy for drug accession while gene therapy can deliver therapeutic genes directly into the joints. Also, long-term expression of the transferred genes is expected. Anti-inflammatory genes, including interleukin-1 receptor antagonist gene, have been used in experimental arthritis models and in a clinical trial for treatment of rheumatoid arthritis. However, during gene therapy of other diseases, tragic accidents associated with viral vectors occurred. Since then, they have hampered clinical application of the gene therapy. Genes for treatment should be selected carefully and gene delivery methods should be optimized to resume clinical trials.     

Cryoprecipitate poor plasma does not improve early response in primary adult thrombotic thrombocytopenic purpura (TTP)

Thrombotic thrombocytopenic purpura (TTP) is a potentially fatal disease that is treated with plasma exchange and typically with replacement with fresh frozen plasma (FFP). This approach results in an approximate 50% response rate following 1 week of therapy and 80% survival. Cryoprecipitate poor plasma (CPP) is plasma from which the cryoprecipitate fraction is removed. CPP has been reported to be successful as salvage therapy in refractory TTP and has been suggested to be superior to FFP in retrospective studies. The present report compares initial therapy of TTP with exchange using replacement with either FFP or CPP in a multi-institutional prospective randomized study performed by the North American TTP Group (NATG Group) from 1993 to 1995. Initial therapy also included corticosteroids. Antiplatelet drugs or vinca alkaloids were not employed. A severity score index, response score, and individual clinical parameters (platelet count, LDH x upper limit of normal, hemoglobin level, and creatinine) were compared at their nadir or peak values, baseline, and days +6 and +13 of therapy. Thirteen patients were randomized to FFP exchange and 14 to CPP exchange. Results were equivalent for all parameters. Survival was equal with three deaths in each group. These data indicate that the efficacy of FFP and CPP are the same in the initial treatment of TTP in adults.     

Auranofin-associated colitis and eosinophilia

Gold compounds, often used in the treatment of rheumatoid arthritis, have been associated with gastrointestinal disturbances in some patients. Use of auranofin, an oral gold preparation, in a 50-year-old woman with rheumatoid arthritis resulted in diarrhea, abdominal tenderness, nausea, and vomiting, which persisted despite discontinuation of auranofin therapy. The presumptive diagnosis was gold-induced colitis and eosinophilia. Administration of cromolyn sodium provided relief. Although this complication may be rare, evolving bowel symptoms in patients receiving auranofin demand prompt attention.     

Reactive hemophagocytic syndrome associated with thrombotic thrombocytopenic purpura during therapeutic plasma exchange.

Hemophagocytic lymphohistiocytosis (HLH) is characterized by fever, cytopenia, splenomegaly, and lymphohistiocytic proliferation with hemophagocytosis. Sporadic, familial, and reactive HLH varieties exist. The latter, also termed the reactive hemophagocytic syndrome (RHS), has been associated with a variety of infectious and noninfectious etiologies. Activation of monocytes in RHS is due to stimulation by high levels of activating cytokines. RHS has not been associated previously with thrombotic thrombocytopenic purpura (TTP). TTP is a multisystem disorder characterized by consumptive thrombocytopenia, microangiopathic hemolytic anemia, neurologic symptoms, renal impairment, and fever. We report on a 33 year old male patient with a classic picture of TTP who initially responded to therapeutic plasma exchange but then became refractory to treatment and developed RHS. It is likely that a specific pathophysiology involving the activation of neutrophils during TPE is present for the development of cytokine-induced hemophagocytosis during TTP treatment. The consequent development of RHS possibly caused early TTP relapse.     

Myocardial injury in HIV‐associated thrombotic thrombocytopenic purpura (TTP)

Thrombotic thrombocytopenic purpura (TTP) has been associated with human immunodeficiency virus (HIV) infection. With the high prevalence of HIV in sub‐Saharan Africa, HIV‐associated TTP is the most common form of this disease seen in the South African population. Several case reports describe myocardial infarction in HIV‐negative TTP patients. The case of the first HIV‐positive patient who presented with clinical signs and symptoms of TTP and myocardial injury is reported in this study. A patient with fragmentation haemolysis and thrombocytopenia presented with angina. Risk factors for ischaemic heart disease were absent. An electrocardiogram (EKG) revealed ST‐segment elevation and a significantly raised Troponin T level. The patient's HIV test was positive and a diagnosis of myocardial injury with HIV‐associated TTP was made. The patient was treated with plasma infusion and steroid therapy. Due to poor response, the therapy was changed to plasma exchange. The patient recovered fully and subsequent coronary angiography revealed normal coronary vessels. Treatment of myocardial infarction in TTP is controversial, but the treatment cornerstone should remain plasma infusion or plasma exchange. As patients are often young and do not have the classical risk factors of ischaemic heart disease, a high level of suspicion and routine exclusion of myocardial ischaemia in these patients are advised.     

Successful management of a Jehovah's Witness with thrombotic thrombocytopenic purpura unwilling to be treated with therapeutic plasma exchange

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease treated successfully with plasma exchange. Jehovah's Witnesses whose religious beliefs preclude them from accepting plasma exchange may require alternative forms of therapy. We report a case of one such patient who presented with TTP, whom we successfully managed with vincristine and responded favorably without the need for plasma exchange.     

Surge of anti-SS-A antibody associated with fulminant thrombotic thrombocytopenic purpura in pregnancy.

Thrombotic thrombocytopenic purpura (TTP) is an uncommon clinical syndrome and is rarely associated with systemic lupus erythematosus (SLE). Diagnosis of TTP in patients with SLE, especially those who are pregnant, is challenging. We report the case of a pregnant woman with a high level of anti-SS-A antibody (162,143 U/mL) and fulminant TTP. The patient responded to plasma exchange treatment. Recent studies indicate that patients with SLE and another serologic abnormality, such as the presence of antiphospholipid antibody, may be at high risk for TTP. We explore the possible pathogenesis of acute TTP in patients with SLE and summarize the risk factors for acute TTP in patients with SLE and the current treatments for SLE-associated TTP.