Several chemotherapeutic drugs have also been shown to cause damage to the epithelial layer by reducing the ability for the cells to produce prostacyclin, ultimately resulting in chemotherapy-associated HUS, or C-HUS.The second category of TMAs is TTP thrombotic thrombocytopenic purpura, which can be divided into 3 categories: congenital, idiopathic, and non-idiopathic. Congenital and idiopathic TTP are generally associated with deficiencies in ADAMTS13, a zinc metalloprotease responsible for cleaving Very Large vWF Multimers in order to prevent inappropriate platelet aggregation and thrombosis in the microvasculature. Natural genetic mutations resulting in the deficiency of ADAMTS13 have been found in homozygous and heterozygous pedigrees in Europe. Researchers have identified common pathways and links between TTP and HUS, while other sources express skepticism about their common pathophysiology.The repression of the vascular endothelial growth factor (VEGF) can also cause glomerular TMA (damage to the glomerular microvasculature). It is likely that the absence of VEGF results in the collapse of fenestrations in the glomerular endothelium, thus causing microvascular injury and blockages associated with TMA.Manifestations resembling thrombotic microangiopathy have been reported in clinical trials evaluating high doses of valacyclovir (8000 mg/day) administered for prolonged periods (months to years) for prophylaxis of cytomegalovirus (CMV) infection and disease, particularly in persons with HIV infection. A number of factors may have contributed to the incidence of thrombotic microangiopathy in those trials including profound immunosuppression, underlying diseases (advanced HIV disease, graft-versus-host disease), and other classes of drug, particularly antifungal agents.
Pathogenesis
The pathogenesis underlying the development of costochondritis remains unclear. Proposed mechanisms of pain include neurogenic inflammation, muscular imbalances, neuropathy of the intercostal nerves, myofascial pain, or mechanical dysfunction. Diagnosis
Costochondritis is predominately a clinical diagnosis only after life-threatening conditions have been ruled out, with physical examination and medical history being considered. Before a costochondritis diagnosis is made, other serious causes of chest pain are investigated. Further evaluation for cardiopulmonary or neoplastic causes is typically based on history, age, and risk factors, with diagnostic imaging and tests, completed to assess for life-threatening emergencies. If there is a suspicion of infection or a rheumatoid condition, laboratory work may be conducted.A physical exam will assess for tenderness or pain upon palpation, with an absence of heat, erythema, or swelling. The physical exam may assess if the pain is worsened with movements of the upper body or breathing, and may be reproduced upon using the crowing rooster maneuver, the hooking maneuver, or the horizontal flexion maneuver. Medical history is considered in diagnosing costochondritis, such as inquiry regarding any recent trauma, coughing, exercise, or activity involving the upper body that may have caused the symptoms. Differential diagnosis
Cardiopulmonary
Life-threatening medical emergencies that may be associated with chest wall pain include acute coronary syndrome, aortic dissection, pneumothorax, or pulmonary embolism. Other cardiopulmonary causes of chest pain similar to that produced by costochondritis may include but are not limited to myocardial infarction, angina, and pericarditis. With costochondritis, the pain is typically worse with respiration, with movement, or within certain positions.