Empirical treatment of granulomatous hepatitis of unknown origin: practice investigation in the French National Society of Internal Medicine |
Thu, Jul 22,2010 |
PURPOSES: Ten to fifteen percent of granulomatous hepatitis are idiopathic. If symptoms like prolonged fever are present, empirical treatment is discussed. The goal of this study is to describe the empirical treatment proposed in this situation by French specialists of internal medicine. METHODS: We conducted a practice investigation among the French national society of internal medicine (SNFMI), using an anonymous questionnaire that related a case of idiopathic granulomatous hepatitis. This questionnaire was proposed to all French internists present at the SNFMI congress in June and December 2004. French specialists of internal medicine had to answer if they would prescribe an empirical treatment and if so, to specify this treatment. RESULTS: Thirty-six French specialists of internal medicine answered to the questionnaire. In the proposed situation, 89% of them initiate an empirical treatment. In 18/36 cases (50%), a first-line anti-tuberculosis empirical treatment is proposed (quadritherapy in 11 cases). In 7 cases (19%), an empirical treatment with prednisone, 0.4 mg/kg/d (N=1) and 1 mg/kg/d (N=6), would be prescribed. Seven internists (19%) would prescribe an empirical treatment with cyclins at the dose of 100 to 400 mg/d. Median duration of the empirical treatment would be 28 days (range: 8-252d). The evaluation parameters mentionned are: fever (69%), weight (59%), seric level of C-reactive protein (59%), and liver biology (53%). In case of failure of first-line empirical treatments, 69% of all questionned internists prescribe a second-line treatments: prednisone at the dose of 0.4 to 2 mg/kg/d (72%), anti-tuberculosis treatments (16%), cyclins 200 mg/d (12%), with a median duration of 28 days. Seven internists (19%) propose to combine two empirical treatments. DISCUSSION: Faced with a problem of idiopathic granulomatous hepatitis, French internists questionned propose four therapeutics options: no treatment, anti-tuberculosis treatment, cyclins or steroids treatment. First-line anti-tuberculosis treatment is a coherent proposition regarding to the high prevalence of tuberculosis. There are only few data available concerning empirical treatment with steroids or cyclins. Specific proposition of such empirical treatments should be defined. CONCLUSIONS: The management of idiopathic granulomatous hepatitis is difficult. Our study shows that therapeutics practices of French internists are heterogenous. The main proposition consists in a first-line anti-tuberculosis empirical treatment, that has to be evaluated after four weeks, and switched with steroids (prednisone, 1 mg/Kg/d) in case of failure. This study is not an expert proposition but contributes to suggest clinical practice guidelines for a rare, complex, heterogenous, and typically internist situation.
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Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. |
Thu, Jul 22,2010 |
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BACKGROUND: Since 1960, oral melphalan and prednisone (MP) has been regarded as the standard of care in elderly multiple myeloma patients. This multicentre randomised trial compared oral MP plus thalidomide (MPT) with MP alone in patients aged 60-85 years. METHODS: Patients with newly diagnosed multiple myeloma were randomly assigned to receive oral MP for six 4-week cycles plus thalidomide (n=129; 100 mg per day continuously until any sign of relapse or progressive disease) or MP alone (n=126). Analysis was intention-to-treat. This study is registered at , number NCT00232934. RESULTS: Patients treated with thalidomide had higher response rates and longer event-free survival (primary endpoints) than patients who were not. Combined complete or partial response rates were 76.0% for MPT and 47.6% for MP alone (absolute difference 28.3%, 95% CI 16.5-39.1), and the near-complete or complete response rates were 27.9% and 7.2%, respectively. 2-year event-free survival rates were 54% for MPT and 27% for MP (hazard ratio [HR] for MPT 0.51, 95% CI 0.35-0.75, p=0.0006). 3-year survival rates were 80% for MPT and 64% for MP (HR for MPT 0.68, 95% CI 0.38-1.22, p=0.19). Rates of grade 3 or 4 adverse events were 48% in MPT patients and 25% in MP patients (p=0.0002). Introduction of enoxaparin prophylaxis reduced rate of thromboembolism from 20% to 3% (p=0.005). CONCLUSION: Oral MPT is an effective first-line treatment for elderly patients with multiple myeloma. Anticoagulant prophylaxis reduces frequency of thrombosis. Longer follow-up is needed to assess effect on overall survival.
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Juvenile dermatomyositis in 12 years old girl |
Thu, Jul 22,2010 |
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We would like to present a selected case of 12-aged girl, with recognition of dermatomyositis (DM). At the age of 11 in the normally developing child, erythematous-oedematous changes have appeared on the face, particularly intensified in the vicinity of the orbital cavities (so called: pseudoglasses), as well as erythema and teleangiectasis on the dorsum of hands and small-sized diarthroidal joints (the Gottron's symptom). Subsequently, lower physical efficiency and distinctly weakness in the child's extremities occurred. In EMG (quadriceps muscle of the thigh) myogenous traits have been proven. Neurological examination revealed as follows: muscular weakness (adynamia), mainly lower limbs (grade 3 in the Lovett's scale, along with decreased loss of muscles tone), lack of the periosteal reflex near lower limbs, positive Gower's symptom and increased anterior spinal curvature. In the biochemical examinations accelerated erythrocyte sedimentation rate (ESR), and a rise of activity in muscles enzymes were stated. In the child's blood serum, we disclosed antinuclear antibodies ANA (type of granular luminescence, titre 160), to be rather evident to presence of autoimmunological process. During examinations of the musculocutaneus specimen, DM-markers have been detected. Capillaroscopy proved specific presence of numerous vessels, multiple capillary tubes, individual gemmated vessels and completely invisible dermatomyositous border. Patient was treated with per os sterid--Encorton at the initial dose of 2 mg/day, every other day during the lapse of 6 weeks to reach the normal CPK-activity, and consequently clinical picture under "on-line" surveillance, gradually reducing a specific medicine up to maintenance dose through 18 months. At present, the patient is subjected to check-up and monitoring by Neurological Outpatient and Rehabilitain Clinic for Children.
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Long-term treatment of Hashimoto's encephalopathy. |
Thu, Jul 22,2010 |
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Hashimoto's encephalopathy (HE) has been described as an encephalopathy, with acute or subacute onset, accompanied by seizures, tremor, myoclonus, ataxia, psychosis, and stroke-like episodes, with a relapsing/remitting or progressive course. HE patients have positive antithyroid antibodies, are usually in a subclinical hypothyroid state, have elevated cerebral spinal fluid (CSF) protein, and have nonspecific electroencephalogram (EEG) and imaging abnormalities in the absence of CNS infection, tumor, or stroke. The authors present two cases of HE, demonstrating an excellent response to high dose steroids acutely followed by long-term treatment with steroids and other immunomodulatory agents. A review of the literature is also provided.
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Malignant non-Hodgkin diffuse lymphoma with extranodal orbital involvement--a clinical case |
Thu, Jul 22,2010 |
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We present the case of a 63 years old patient, hospitalized in our Clinic with the suspicion of preseptal cellulitis. The subsequent evolution of the disease required extensive investigations which provide the definitive diagnosis of non-Hodgkin, diffuse B-cell lymphoma, with extranodal orbital involvement. In this case, the treatment of choice it must be systemic chemotherapy.
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Clinical outcome of primary gastric lymphoma treated with chemotherapy alone or surgery followed by chemotherapy. |
Thu, Jul 22,2010 |
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BACKGROUND: The role of surgical resection in the treatment of primary gastric lymphoma (PGL) remains unclear. This retrospective study evaluated the clinical outcome of PGL treated with chemotherapy alone or surgery followed by chemotherapy. METHODS: During 1986-2003, 59 patients with PGL (other than mucosa-associated lymphoid tissue type lymphoma) were identified from hospital files. The medical records, pathologic sections, radiographic images and treatment modalities of these patients were reviewed. Patients were categorized into localized (stage IE and IIE-1) and advanced (stage IIE-2 or beyond) stage groups. Survival was estimated by the Kaplan-Meier method. RESULTS: The study included 55 patients who received treatment at the same institute. Among them, 32 had localized PGL (15 stage IE, 17 stage IIE-1) and 23 had advanced disease. The median survival of the localized stage group was not reached during a mean follow-up of 168.1 +/- 16.7 months (95% confidence interval [CI], 135.4-200.8 months), while that of the advanced stage group was 33.0 +/- 6.8 months (95% CI, 19.7-46.5; p < 0.001, log-rank test). Among patients with localized PGL, the 5-year overall survival rate of those receiving chemotherapy alone (n = 19) or combination therapy (surgery followed by chemotherapy, n = 13) was 73.4% and 87.5%, respectively (p = 0.229). The 5-year disease-free survival was 68.4% and 84.6%, respectively (p = 0.540). However, post-chemotherapy life-threatening hemorrhage occurred in five of the 32 patients (15.6%) in the localized stage group: four in the chemotherapy-alone group, and one in the combination therapy group, all of whom had failed to achieve complete response. CONCLUSION: The clinical outcome of localized PGL treated by chemotherapy alone is similar to that treated by surgery followed by chemotherapy in terms of tumor response, disease-free survival and overall survival, suggesting that surgery be reserved for those with residual tumors after chemotherapy.
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Acute steroid responsive small-fiber sensory neuropathy: a new entity? |
Thu, Jul 22,2010 |
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Small-fiber neuropathy is often idiopathic and commonly follows a chronic course. Treatment is often effective in treating the core symptom of pain, but it has no effect on the pathologic process. We describe four patients with acute small-fiber neuropathy who responded dramatically to steroid therapy. All patients had acute onset neuropathic pain, normal nerve conduction studies, and evidence of small-fiber dysfunction in quantitative sensory testing and skin biopsy. Symptoms were distal and symmetrical in three patients and generalized in one patient. In two cases, the neuropathy presented as an erythromelalgia-like syndrome. Marked clinical improvement occurred 1-2 weeks after oral prednisone therapy was initiated. Three patients remained symptom free, and one patient experienced recurrence of neuropathy after prednisone was tapered.
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Long-term complete remission in IgD-myeloma. |
Thu, Jul 22,2010 |
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Long-term complete remission in IgD multiple myeloma (MM) is rare. This case report describes a patient with a stage IIIB IgD-MM, who was treated with conventional melphalan and prednisone chemotherapy. The monoclonal protein disappeared after four cycles and therapy was discontinued after 14 cycles. Re-evaluation after a follow up of more than 8 years demonstrates a continuing complete remission suggesting a cure. This is remarkable, considering that several adverse prognostic factors were present. In addition a concise review on IgD-MM is given.
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Intravenous melphalan, thalidomide and prednisone in refractory and relapsed multiple myeloma. |
Thu, Jul 22,2010 |
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OBJECTIVES: Thalidomide combined with conventional chemotherapies including oral melphalan shows significant anti-myeloma activity. To address this issue, feasibility and efficacy of a three drug combination consisting of intravenous (i.v.) melphalan, thalidomide and prednisone [M(i.v.)PT] was evaluated in advanced myeloma patients. PATIENTS AND METHODS: Twenty-four advanced myeloma patients were treated with multiple cycles of a regimen consisting of low dose i.v. melphalan (20 mg/m2) at d 1, thalidomide at the dose of 50-100 mg/d given continuously and oral prednisone at the planned dose of 50 mg/d every other day. Intravenous melphalan was administered every fourth month. Median time from diagnosis was 40 months (range: 8-144 months). Fifteen patients (66%) had previously been treated with a combination of thalidomide and dexamethasone or with thalidomide alone. RESULTS: Overall, on an intent-to treat basis, 14 patients responded: three achieved near complete remission (nCR), seven achieved partial response (PR), four minimal response (MR). Six patients showed stable disease (SD) and four-disease progression. Interestingly, of five patients who had previously progressed while on thalidomide and prednisone, one reached nCR, two PR and one MR. After a median follow up of 14 months, median progression free survival was 9 months. Response duration was longer than that induced by the previous line of treatment in eight patients (33%). Thalidomide-associated toxicity mainly consisted of constipation, tingling and sedation. CONCLUSIONS: M(i.v.)PT is an effective regimen, which can overcome resistance to thalidomide plus prednisone in advanced myeloma with acceptable toxicity.
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Recurrence of proteinuria following renal transplantation in congenital nephrotic syndrome of the Finnish type. |
Thu, Jul 22,2010 |
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We report a Caucasian boy of Italian descent with congenital nephrotic syndrome of the Finnish type (NPHS1, CNF, MIM 256300) who developed recurrence of proteinuria and hypoalbuminemia on the seventh post-operative day following living related renal transplantation from his paternal aunt. The allograft biopsy was normal except for effacement of podocyte foot processes on electron microscopy. He was treated by the substitution of mycophenolate mofetil with cyclophosphamide for 12 weeks, in addition to cyclosporine, prednisone and daclizumab. His proteinuria resolved quickly following the initiation of cyclophosphamide treatment, and he remains in remission 4 years after receiving his transplant. His native and allograft kidneys were evaluated for nephrin expression by immunohistochemistry, DNA analysis for the NPHS1 mutation, serum for the presence of auto-antibodies to nephrin by both enzyme-linked immunosorbent assay (ELISA) and fetal glomeruli immunofluorescence assay, and serum for glomerular permeability to albumin (Palb) activity using a functional in vitro assay for Palb. Nephrin expression was completely absent in the native kidney, while it was decreased in the allograft compared with normal. DNA analysis of the NPHS1 gene revealed mutations 3248G>T and 3250delG in exon 24, causing G1083V and 1084Vfs, respectively, inherited from his father, and 3478C>T in exon 27, that leads to R1160X, inherited from his mother. Serum was negative for auto-antibodies to nephrin. Interestingly, the Palb activity was increased at the time of recurrence of proteinuria following transplantation (Palb 0.73+/-0.10) and remained elevated when retested more than 3 years later (Palb 0.54+/-0.09). This is the first report of increased Palb activity in recurrence of proteinuria following transplantation in NPHS1. We speculate the role of increased Palb activity in the recurrence of proteinuria following transplantation in NPHS1.
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