Use Of Immunosuppressive Treatment Research Articles

Contemporary Tools for the Diagnosis and Management of Invasive Mycoses

Invasive fungal infections have become a major cause of morbidity and mortality over the past 3 decades. Organ transplantation, the use of aggressive chemotherapy, and the availability and widespread use of immunosuppressive treatments for many medical ailments have resulted in large populations of patients who are at risk for fungal disease. Early diagnosis and prompt therapy are instrumental to successful treatment of these infections, but conventional methods for diagnosis of fungal disease are slow and lack sensitivity. Important advances in diagnosing invasive mycoses, particularly in laboratory-based testing, have been realized over the years. Antigen-based assays, new laboratory methods for identification of fungi, and reference guidelines for susceptibility testing have been developed and validated for use in clinical laboratories. We review these technological advances and our understanding of their clinical application and impact.

Restrictive use of immunosuppressive treatment in patients with idiopathic membranous nephropathy: high renal survival in a large patient cohort.

Immunosuppressive treatment initiated at an early stage in patients with idiopathic membranous nephropathy (iMN) improves renal survival. Treatment should ideally be restricted to high-risk patients. To evaluate the efficacy of a restrictive immunosuppressive treatment strategy for patients with iMN. Prospective cohort study evaluating a predefined treatment protocol. From 1988, we adopted a restrictive treatment strategy: immunosuppressive treatment, mainly consisting of cyclophosphamide and steroids, was advised only in patients with renal insufficiency or severe intolerable nephrotic syndrome. We evaluated this strategy in a large patient cohort. To exclude any bias, we included all adult patients with iMN biopsied in the study period with a serum creatinine (Scr) < 135 micromol/l, a proteinuria > or = 3.0 g/day and/or a serum albumin (Salb) < or = 30 g/l at the time of biopsy. Analysis was according to the intention-to-treat principle. We studied 69 patients. At the time of biopsy, mean age was 51 years, Scr 90 micromol/l, Salb 23 g/l and proteinuria 6.7 g/day. Average follow-up was 5.5 years. Thus far 33 (48%) patients have received immunosuppressive therapy, mainly because of renal insufficiency (n = 24). Status at the end of follow-up was: complete remission n = 22 (32%), partial remission n = 24 (35%), nephrotic syndrome n = 15 (22%), persistent proteinuria n = 1 (1.4%), ESRD n = 6 (8.7%), death n = 1 (1.4%; due to bladder carcinoma after cyclophosphamide therapy). Patient survival was 100% at 5 and 7 years. Renal survival was 94% at 5 years and 88% at 7 years. In patients with iMN, a restrictive treatment policy assures a favourable prognosis, while preventing exposure to immunosuppressive therapy in >50% of the patients.

Diagnosis and therapy of vasculitic neuropathy. Consensus statement of the German Centers for Neuromuscular Disease

Vasculitic neuropathies are immune mediated diseases of the peripheral nervous system, in which inflammation of the blood vessels causes damage to the nerves. We distinguish neuropathies associated with primary and secondary systemic vasculitis, with rheumatic diseases, with malignant disorders, drug-induced vasculitis and the non-systemic vasculitic neuropathies (NSVN). The typical clinical picture consists in an asymmetric or multifocal, painful sensorimotor neuropathy with an acute, subacute or chronic course and acute relapses. Neurophysiology reveals an active, asymmetric, axonal sensorimotor neuropathy. The disorders usually respond to immunosuppressive treatment. A diagnosis of definite vasculitis can be made with evidence of vasculitis in a biopsy specimen. The absence of positive morphological evidence, however, does not exclude the diagnosis. There is no single laboratory test that can prove or exclude vasculitis, in NSVN even an elaborate panel of blood tests can show normal findings. Systemic vasculitis has an incidence of 4/100,000 per year and, untreated, has a poor prognosis, which is greatly improved by the use of immunosuppressive treatment. The prognosis of NSVN is generally better, although many patients need long term immunosuppression. Current treatment recommendations for vasculitic neuropathies are presented.

Difficult asthma.

Asthma is usually easy to manage, but approximately 5% of patients are not controlled even on high doses of inhaled corticosteroids. It is important to assess these patients carefully in order to identify whether there are any correctable factors that may contribute to their poor control. It is critical to make a diagnosis of asthma and to exclude other airway diseases, particularly chronic obstructive pulmonary disease (COPD), and vocal cord dysfunction ("pseudo-asthma"). Poor adherence to therapy, particularly inhaled corticosteroids, is a common reason for a poor response. There may be unidentified exacerbating factors, including unrecognized allergens, occupational sensitizers, dietary additives, drugs, gastro-oesophageal reflux, upper airway disease, or other systemic diseases, that need to be identified and avoided or treated. Psychological factors may be important in some patients, but it is difficult to know whether these are causal or secondary to troublesome disease. Some patients have instability of their asthma, with resistant nocturnal asthma, premenstrual exacerbations or chaotic and unpredictable instability (brittle asthma). A few patients are completely resistant to corticosteroids, but more patients are relatively resistant and require relatively high doses of corticosteroids to control their symptoms (steroid-dependent). Some patients develop progressive loss of lung function, as in patients with COPD. Management of patients with difficult asthma should be supervised by a respiratory specialist and should involve careful assessment to confirm a diagnosis of asthma, identification and treatment of exacerbating factors, particularly allergens, and recording of peak expiratory flow patterns. A period of hospital admission may be the best way to assess and manage these patients. Treatment involves optimizing corticosteroids therapy, assessing additional controllers such as long-acting inhaled or subcutaneous beta2-agonists or subcutaneous, theophylline and antileukotrienes. In some patients, the use of immunosuppressive treatments may reduce steroid requirements, although these treatments are rarely effective and have side-effects. In the future, the nonsteroid anti-inflammatory treatments now in development may be useful in these patients.

Risk of cervical intraepithelial neoplasia in women with glomerulonephritis

OBJECTIVE--To investigate the occurrence of cervical intraepithelial neoplasia in women with glomerulonephritis and its possible association with immunosuppressive treatment. DESIGN--Retrospective study of cytological or histological specimens from women presenting with glomerulonephritis and a group of case and age matched controls. SETTING--University department of pathology, Norway. PATIENTS--81 women presenting with glomerulonephritis from 1981 to 1988, from whom gynaecological cytological or histological specimens were available. A group of 162 case and age matched controls. MAIN OUTCOME MEASURES--Age when glomerulonephritis of cervical intraepithelial neoplasia was diagnosed, type and characteristics of kidney lesion, stage of cervical intraepithelial neoplasia and presence of human papillomavirus, use of immunosuppressive treatment. RESULTS--Cervical intraepithelial neoplasia was more common in women with glomerulonephritis than in their controls (16/81 (20%) v 7/162 (4%), p less than 0.001) and was more advanced in those with glomerulonephritis than in the controls (9/81 (11%) of the study group had grade III cervical intraepithelial neoplasia compared with 1/162 (1%) of the controls). The increased occurrence of cervical lesions was independent of the use of immunosuppressive treatment, but the individual lesions tended to be more advanced when it was used (four of the seven cervical lesions in women with glomerulonephritis who had received immunosuppressive treatment were carcinoma in situ). Of the nine cervical lesions tested, seven were virus associated. CONCLUSION--Women with glomerulonephritis should have regular cervical smears, irrespective of their use of immunosuppressive treatment.

Major trends in nosocomial viral infections

Viruses have recently become appreciated as nosocomial pathogens. There is insufficient data to characterize trends in rates of viral nosocomial infections, but there have been major trends in methodologies and concepts. New groups of patients, such as infants and the elderly, are becoming appreciated as being at risk for serious nosocomial viral infections, whereas other groups, such as immunodeficient patients are expanding because of the epidemic of human immunodeficiency virus (HIV) infection and expanded use of immunosuppressive treatment. The continued addition of new viruses, such as HIV, human parvovirus B19, and rabies virus, to the list of potential nosocomial pathogens suggest that most human viruses can probably be serious nosocomial pathogens under the right circumstances. Advances in medical treatments and procedures, such as cadaveric dura mater grafts and laser treatment of warts, have provided new avenues for nosocomial transmission of viruses. Improved and wider availability of diagnostics promises to be a major force in improving our understanding and ability to prevent viral nosocomial infections. With these advances, viral diagnostic laboratories should become an important member of the infection control team. In parallel with trends in methodologies and concepts, there have been major advances in our understanding of ways to prevent some nosocomial viral infections. Application of these prevention measures is an important challenge to the infection control practitioner.

Risk of cervical intraepithelial neoplasia in women with glomerulonephritis.

To investigate the occurrence of cervical intraepithelial neoplasia in women with glomerulonephritis and its possible association with immunosuppressive treatment. Retrospective study of cytological or histological specimens from women presenting with glomerulonephritis and a group of case and age matched controls. University department of pathology, Norway. 81 women presenting with glomerulonephritis from 1981 to 1988, from whom gynaecological cytological or histological specimens were available. A group of 162 case and age matched controls. Age when glomerulonephritis of cervical intraepithelial neoplasia was diagnosed, type and characteristics of kidney lesion, stage of cervical intraepithelial neoplasia and presence of human papillomavirus, use of immunosuppressive treatment. Cervical intraepithelial neoplasia was more common in women with glomerulonephritis than in their controls (16/81 (20%) v 7/162 (4%), p less than 0.001) and was more advanced in those with glomerulonephritis than in the controls (9/81 (11%) of the study group had grade III cervical intraepithelial neoplasia compared with 1/162 (1%) of the controls). The increased occurrence of cervical lesions was independent of the use of immunosuppressive treatment, but the individual lesions tended to be more advanced when it was used (four of the seven cervical lesions in women with glomerulonephritis who had received immunosuppressive treatment were carcinoma in situ). Of the nine cervical lesions tested, seven were virus associated. Women with glomerulonephritis should have regular cervical smears, irrespective of their use of immunosuppressive treatment.