Thrombotic thrombocytopenic purpura: a diagnostic and therapeutic challenge

With the discovery of the ultra-large von Willebrand factor (vWF) in the plasma of thrombotic thrombocytopenic purpura (TTP) patients and the pivotal role played by the ADAMTS13 metalloproteinase, many new challenges are facing both the researcher and the clinician for the diagnosis and treatment of this condition. As a result of these new discoveries, the range of disorders manifesting with many of the clinical features of the disease can now be reclassified into the idiopathic TTP, congenital TTP, and non-idiopathic TTP, based on the level of ADAMTS13 activity. The latter group includes drug-associated TTP. In this article, the background of the pathogenesis, and diagnostic and therapeutic approaches are reviewed. An emerging concept of the pathogenesis of TTP is presented. The merits of various diagnostic procedures including the assay of the ADAMTS13 activity and the immunoglobulin G inhibitory antibodies are discussed. Regarding the therapeutic aspect, although plasma exchange remains the mainstay, the question of addition of immunosuppressive agents comes up, especially in those patients who are refractory to plasma exchange and those that repeatedly relapse. A call for clinical trials to address the question of efficacy of various agents is made.     

Left posterior fascicular tachycardia: a diagnostic and therapeutic challenge

A wide QRS complex tachycardia with right bundle-branch block morphology and left axis deviation observed in a young patient without structural heart disease may pose a diagnostic and therapeutic challenge. The surface ECG may provide several diagnostic clues to make a correct diagnosis of left posterior fascicular tachycardia and may help to differentiate it from both a supraventricular tachycardia with aberrant conduction and a typical ventricular tachycardia related to coronary artery disease. Although this tachycardia is sensitive to verapamil, this medication may probably cause transient infertility in males. The presence of a Purkinje potential preceding the QRS complex during tachycardia and optimal pace mapping may guide radio-frequency ablation resulting in a definite cure.     

Adult idiopathic subglottic stenosis: a diagnostic and therapeutic challenge

A 22-year-old woman presented with effort dyspnea unresponsive to bronchodilators. Harsh respiratory sounds were audible at the neck. Thoracic and cardiac evaluation was normal. Spirometry revealed an obstructive ventilatory defect, and the flow-volume loop indicated upper airway obstruction. Bronchoscopy and tracheal computed tomography revealed a stenosis of the subglottic larynx. A biopsy specimen of the stenotic area of the trachea showed a normal mucosa and non-specific chronic inflammation. The tracheal stenosis was managed by means of endobronchial laser therapy, which led to the resolution of the patient's symptoms. As we could not identify any specific pathogenetic process, our final diagnosis was idiopathic subglottic tracheal stenosis.     

Infective endocarditis: a diagnostic and therapeutic challenge for the new millennium

This review on infective endocarditis (IE) is based on clinical studies carried out in G?teborg since 1984, data obtained from a Swedish national registry of IE since 1995 and existing literature. IE is still a great challenge in medicine, although improved bacteriological and echocardiographical techniques have facilitated diagnosis. In Sweden the incidence of IE is about 6 per 100,000 inhabitants a year. During recent decades IE has changed character. Patients are older, fever is often the only major symptom and a new murmur is less frequent. Streptococci, including viridans species and staphylococci, are still the most common bacteria found. Antibiotic treatment for 4-6 weeks may reduce mortality of IE to 30-50%. For further reduction, heart surgery is necessary in 20-25% of patients in order to remove infected tissues and restore valve function. Rapid diagnosis, careful antibiotic treatment and optimal surgery may reduce mortality associated with treatment to 10%. Antibiotic treatment is still mainly empiric. Penicillin and aminoglycoside for 2 weeks only seem to be effective in uncomplicated IE caused by alpha-streptococci. Otherwise, 4 weeks of treatment is needed, but aminoglycoside treatment may be reduced to 1 week in general and 2 weeks for enterococcal infections.     

Leiomyosarcoma of the superior mesenteric vein: a diagnostic and therapeutic challenge

We report here a case of a very rare entity, a leiomyosarcoma of the mesentericoportal trunk, which was initially misdiagnosed as an unresectable pancreatic cancer invading the mesenteric vein, and which was finally treated by pancreatectomy with mesentericoportal reconstruction. The pitfalls of diagnosis and modalities of resection are discussed.     

Congenital intestinal diarrhoeal diseases: A diagnostic and therapeutic challenge

Congenital diarrhoeal disorders are a heterogeneous group of inherited malabsorptive or secretory diseases typically appearing in the first weeks of life, which may be triggered by the introduction of distinct nutrients. However, they may also be unrecognised for a while and triggered by exogenous factors later on. In principle, they can be clinically classified as osmotic, secretory or inflammatory diarrhoea. In recent years the disease-causing molecular defects of these congenital disorders have been identified. According to the underlying pathophysiology they can be classified into four main groups:1) Defects of digestion, absorption and transport of nutrients or electrolytes2) Defects of absorptive enterocyte differentiation or polarisation3) Defects of the enteroendocrine cells4) Defects of the immune system affecting the intestineHere, we describe the clinical presentation of congenital intestinal diarrhoeal diseases, the diagnostic work-up and specific treatment aspects.     

Mycobacterium genavense infection in a solid organ recipient: a diagnostic and therapeutic challenge

Renal transplant recipients are highly susceptible to infections caused by uncommon pathogens because of their immunocompromised state. We report a case of disseminated Mycobacterium genavense infection in a patient with a combined renal and cardiac transplant. Diagnosing M. genavense infections remains a challenge because of the absence of specific clinical symptoms in combination with the difficulties of culturing the organism using standard mycobacterial culture procedures. This clinical case demonstrates the importance of molecular techniques as part of the initial work‐up in order to rapidly establish the diagnosis.     

The acute porphyrias: a diagnostic and therapeutic challenge in internal and emergency medicine

The porphyrias are a heterogeneous group of metabolic diseases resulting from a variable catalytic defect of one of the eight enzymes involved in the heme biosynthesis pathway; they are mostly inherited diseases, but in some circumstances the metabolic disturbance may be acquired. The specific patterns of tissue overproduction (and hence accumulation and excretion) of toxic heme precursors, associated with each enzymatic deficiency, are responsible for the characteristic biochemical and clinical features of each of these diseases. Moreover, even in the presence of a specific inherited enzymatic defect, many different environmental factors (such as drugs, calorie restriction, hormones, sunlight exposition, infections, etc.) often play a key role in triggering the clinical expression of the various forms of porphyrias. The porphyrias are often misdiagnosed diseases, due their multiform clinical manifestations, able to mimic many other more common diseases. For this reason, many different specialists, such as surgeons, psychiatrists, gastroenterologists, neurologists, emergency physicians and dermatologists may be variably involved in the diagnostic process, especially for the forms presenting with acute and life-threatening clinical features. According to the clinical features, the porphyrias can be classified into neuropsychiatric (characterized by neurovisceral crises involving autonomic and central nervous system but also the liver and the kidney with possible consequences in terms of neurological, psychic, cardiac, respiratory, liver and kidney functions), dermatological (mostly presenting with cutaneous lesions due to photosensitivity), and mixed forms. From a strictly clinical point of view, porphyrias presenting with neurovisceral attacks are also referred as acute porphyrias: they are the object of the present review. An accurate diagnosis of acute porphyria requires knowledge and the use of correct diagnostic tools, and it is mandatory to provide a more appropriate therapeutic approach and prevent the use of potentially unsafe drugs, able to severely precipitate these diseases, especially in the presence of life-threatening symptoms. To date, availability of a relatively stable haem preparation (haem arginate) has significantly improved the treatment outcome of acute porphyric attacks, so the knowledge about the diagnosis and the management of these diseases may be relevant for physicians working in internal medicine, neurology and emergency units.     

Pulmonary mycobacteriosis in a patient affected by mycosis fungoides: a diagnostic and therapeutic challenge

Among patients with cutaneous T-cell lymphoma (CTCL), sepsis and pulmonary infections are the first cause of death. We report on a patient with CTCL who, after more than 10 years of aggressive antineoplastic treatments, showed extensive pulmonary infiltrations on staging CT scan. Repeated CT scans were inconclusive for an infectious process, and the patient was still asymptomatic. The diagnosis of mycobacteriosis was made on the microbiologic exam of bronchoalveolar lavage. Specific treatment was started with contemporary dosage reduction of chemotherapy. After six months of antibiotic treatment the pulmonary lesions improved, whereas CTCL progressed. Therefore, a new antineoplastic regimen was started obtaining control of CTCL, without aggravation of the pulmonary lesions. We highlight the diagnostic and therapeutic pitfalls encountered when pulmonary mycobacteriosis complicates the course and treatment of CTCL.