Unusual presentation of eosinophilic fasciitis: two case reports and a review of the literature.

INTRODUCTION: Eosinophilic fasciitis is an uncommon disorder with unknown etiology and a poorly understood pathogenesis. We present the cases of two patients with eosinophilic fasciitis with unusual presentation, and describe the clinical characteristics and laboratory findings related to them. CASE PRESENTATION: The first case involves a 29-year-old Turkish man admitted with pain, edema and induration of his right-upper and left-lower limbs. Unilateral edema and stiffness with prominent pretibial edema was noted upon physical examination. A high eosinophil count was found on the peripheral smear. The second case involves a 63-year-old Turkish man who had pain, edema, erythema, and itching on his upper and lower extremities, which developed after strenuous physical activity. He had cervical lymphadenopathy and polyarthritis upon physical examination, and rheumatoid factor and antinuclear antibody upon laboratory examination. CONCLUSION: Eosinophilic fasciitis can present with various symptoms. When patients exhibit eosinophilia, arthralgia and myalgia, eosinophilic fasciitis should be considered as a possible diagnosis.

Low dose vincristine-induced severe polyneuropathy in a Hodgkin lymphoma patient: a case report (vincristine-induced severe polyneuropathy).

Chemotherapeutic drugs are the most common toxic agents for peripheral nerves. Vincristine is a vinca alkaloid drug that is used for the treatment of several malignancies in combination with other chemotherapeutic agents. Treatment with intravenous (IV) vincristine at doses above 5 mg leads to a dose-dependent neuropathy with sensory symptoms but higher cumulative doses at around 30 to 50 mg are needed for the development of motor symptoms. The standard maximum adult IV vincristine dose is 2 mg IV per dose given at weekly intervals. However, administration of a single 2-mg dose IV vincristine may rarely result in the development of peripheral neuropathy. Few case reports have been presented on vincristine-associated severe paralysis in patients with preexisting hereditary neuropathy like Charcot-Marie Tooth (CMT) disease, who received doses even lower than 2 mg. Herein, we reported a Hodgkin lymphoma patient who developed severe polyneuropathy after receiving 2 mg vincristine treatment and was subsequently found to carry the CMT1A duplication responsible for CMT disease.

Screening for Celiac disease in Hodgkin and non-Hodgkin lymphoma patients.

BACKGROUND/AIMS: Celiac disease is an abnormal T cell-mediated immune response against dietary gluten in genetically predisposed individuals. The aim of our prospective study was to evaluate the frequency of Celiac disease in patients with lymphoma and to determine the usefulness of the anti-gliadin and anti-endomysial antibodies (EMA) for diagnosis of Celiac disease in this patient group. METHODS: We studied 119 patients with previously or newly diagnosed non-Hodgkin's lymphoma and 60 patients with Hodgkin's lymphoma who presented at the hematology and medical oncology divisions of Dicle University Hospital in Turkey between December 2002 and January 2006. Serological screening for Celiac disease was performed in all patients by searching for serum anti-gliadin immunoglobulin A and immunoglobulin G, and EMA immunoglobulin A and immunoglobulin G. RESULTS: In the Hodgkin's lymphoma group, anti-gliadin immunoglobulin A was detected in 9 (15%) patients (3 male, 6 female), and antigliadin immunoglobulin G was detected in 21 (35%) patients (15 male, 6 female). In the non-Hodgkin's lymphoma group, antigliadin immunoglobulin A was detected in 6 (5%) patients (2 M male 4 female), and anti-gliadin immunoglobulin G was detected in 30 (25.2%) patients (18 male, 12 female). EMA immunoglobulin A and immunoglobulin G were not detected in the Hodgkin's lymphoma and non-Hodgkin's lymphoma groups. CONCLUSIONS: Our report is the first to describe the frequency of Celiac disease in patients with lymphoma in the southeast region of Turkey. In our study, there was no evidence that Celiac disease is a pre-malignant condition for lymphoma. Serological screening for Celiac disease in lymphoma patients does not seem to be necessary.

Prevalence of antineutrophil cytoplasmic antibody positivity in patients with Hodgkin's and non-Hodgkin lymphoma: a single center experience.

Hematological malignancies are associated with the release of different autoantibodies and rheumatological manifestations. Systemic vasculitides are rare in hematological malignancies, and antineutrophil cytoplasmic antibodies (ANCA) have not been described sufficiently in hematological malignancies. In this present prospective study, we examined the prevalence of ANCA and related disease in Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients in the southeast region of Turkey. We examined 119 patients with previously or newly diagnosed NHL and 60 patients with HL for the presence of ANCA and related autoimmune diseases between December 2002 and February 2007. ANCA positivity was detected in only 8 patients (4.4%); and all of these ANCA positivities were detected in patients in the HL group (13.3%); p-ANCA positivity was detected in 6 patients (3.3%); and c-ANCA positivity was detected in 2 patients (1.1%). There was statistically significant difference between patients with HL and NHL in terms of p-ANCA (p = 0.001) but none in c-ANCA (p = 0.111) positivity. None of the ANCA positive patients had vasculitides or rheumatic manifestations. In addition, we did not detect any ANCA positivity in the NHL group. In conclusion, ANCA positivities were detected only in HL patients; but we did not detect the association between ANCA positivities and rheumatic manifestations or vasculitis and also the different treatment responses in HL patients.

Use of N-terminal pro-brain natriuretic peptide to assess left ventricular function after adjuvant doxorubicin therapy in early breast cancer patients: a prospective series.

BACKGROUND AND OBJECTIVE: Anthracyclines are well established and highly efficacious antineoplastic agents for various haematopoietic and solid tumours, such as breast cancer. The main adverse effect of anthracycline therapy is cardiotoxicity. The aim of this prospective study was to determine the role of plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) in assessing left ventricular function in early breast cancer patients receiving adjuvant anthracycline treatment. METHODS: Thirty-three newly diagnosed breast cancer patients who received a total doxorubicin dosage of 240 mg/m2 over four treatment cycles as part of adjuvant chemotherapy after curative breast surgery were included in this study. Venous NT-proBNP levels were measured before and at the end of doxorubicin therapy. Left ventricular function was measured by echocardiography conducted 3 weeks after surgery and at the end of doxorubicin therapy. RESULTS: NT-proBNP levels were significantly higher in patients (n=10) with decreased left ventricular ejection fraction (LVEF) [p=0.02]. There was no difference in LVEF (p=0.164) or NT-proBNP levels (p=0.844) between the patients who had high NT-proBNP levels and those who had normal NT-proBNP levels before doxorubicin chemotherapy. None of the factors studied (breast cancer grade, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status, age) was found to be significantly related to NT-proBNP. CONCLUSION: The association between higher NT-proBNP levels and reduced LVEF in asymptomatic breast cancer patients after doxorubicin administration could be an early indication of subclinical acute anthracycline cardiotoxicity. Furthermore, breast cancer patients experiencing a progressive increase in NT-proBNP levels might be in a higher risk group for acute anthracycline cardiotoxicity.

Thrombophilias and arteriovenous fistula dysfunction in maintenance hemodialysis.

Most episodes of fistula thrombosis are consequences of underlying physioanatomic abnormalities. However, some dialysis access thrombosis develops independent from any obvious anatomic cause. We aimed to clarify the role of thrombophilias in primary and secondary AVF failure. One hundred eighty nine arteriovenous fistulas in 116 adults on maintenance hemodialysis were analyzed. All subjects were evaluated for many thrombotic factors. Fistula information was obtained both from the patients' self reports, and from their medical records. Twenty-seven AVFs in 18 cases (14.3%) had pAVFF. The percentage of subjects with a BMI < 20 kg/m(2) was significantly lower than no-pAVFF group (P = 0.03). ATIII levels and albumin values were significantly lower in patients with sAVFF compared to those with no sAVFF. Other parameters were similar. There was no statistically significant difference between pAFFF versus No-pAFFF and sAFFF versus No-sAFFF groups with respect to all mutant alleles count. Routine extended analyses of all thrombophillic factors are not recommended in AVFF.

Thrombosis of temporal artery and renal vein in Kimura-disease-related nephrotic syndrome.

Kimura disease (KD) is an angiolymphoid proliferative disorder of unknown etiology, occurs mainly in Asian patients, presenting with subcutaneous slowly growing masses, with a predilection for preauricular and submandibular regions. The clinical course of the disease is thought to be benign. Concomitant peripheral blood eosinophilia and elevated serum immunoglobulin E levels are often observed. Main systemic manifestation of the KD is renal involvement. Renal abnormalities, notably proteinuria and nephrotic syndrome have been found to be associated with KD. We report a 42-year-old man with KD and a steroid-sensitive membraneous nephrotic syndrome with bilaterally temporal artery and renal vein thrombosis. This is the first reported case of KD associated nephrotic syndrome complicated with wide arterial and venous thrombosis from Anatolia.

A case of essential mixed cryoglobulinemia and associated acquired von-Willebrand disease treated with rituximab.

Current treatment options of essential mixed cryoglobulinemia (EMC); include immunosuppressive approaches, such as corticosteroids, cyclophosphamide, plasma exchange, other cytotoxic drugs in moderate to severe manifestations. Some controlled studies have been carried out to assess the efficacy of anti-CD20 monoclonal antibody, rituximab in patients with hepatitis C (HCV) related cryoglobulinemia (CG) and in patients with autoimmune disorders. Recent trials and some case reports demonstrate a beneficial role for rituximab in HCV related mixed CG. Although, the published evidence for treatment of EMC with rituximab is restricted to case reports, which have shown positive results. Several diseases include lymphoproliferative and myeloproliferative disorders, solid tumors, immunological disorders, cardiovascular disorders and some drugs associated with acquired von Willebrand disease (avWD). CG, which is a kind of immune complex disease, may be related with development of autoantibodies to various autoantigens. In this present case report, we showed the efficacy of rituximab in a 21-year-old female patient, suffered from neuropathy and arthralgia related with EMC, and developed avWD, presented with mucosal bleeding associated with CG. von Willebrand factor activity of our patient also increased with controlling the underlying disease, EMC by rituximab. This case demonstrate that rituximab may be an effective treatment option in EMC and avWD mainly related to CG.

The effects of nonsteroidal anti-inflammatory drugs on platelet function and severity of upper gastrointestinal haemorrhage.

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal (GI) damage primarily due to the inhibition of prostaglandin synthesis in gastric mucosa, which is an important factor in mucosa protection. Platelets are a cardinal feature of vascular repair. A variety of angiogenic stimulators are stored in platelets and are released during clotting at the wound. When there is a defect in any of these functions and/or platelet number, haemostasis is usually impaired and there may be an associated increased risk and severity of bleeding. While the mechanism of mucosal injury and bleeding are well documented with the use of NSAIDs, very little is known about the platelet function abnormalities and their effects on severity of upper GI bleedings. We performed a prospective analysis of 49 patients who had a history of NSAIDs use to investigate the association between the platelet function impairment associated with NSAIDs and severity of upper GI haemorrhages. Thirty-six of 49 patients (73.5%) had deteriorated platelet function. Mean severity score of patients with deteriorated platelet functions was 3.39, and that of patients with normal platelet functions was 2.46. Mean severity score was statistically significantly higher in patients with deteriorated platelet functions. In conclusion, impaired platelet functions associated with NSAIDs may cause more severe upper GI bleeding. Clinicians should be alert for GI complications especially in older patients and in those with a history of ulcer bleeding.

Two cases of bacterial meningitis accompanied by thalidomide therapy in patients with multiple myeloma: is thalidomide associated with bacterial meningitis?

Morbidity and mortality in multiple myeloma is often attributed to life-threatening infections. A defect in humoral immunity has been proposed for the predisposition to bacterial infections. Most of the infections are of bacterial origin, and the most serious are septicemia, meningitis, and pneumonia. Thalidomide is a drug with pleiotropic effects. The immunomodulatory effects of thalidomide are at least partially mediated through its ability to down-regulate the pathogenic over-production of tumor necrosis factor-alpha (TNF-alpha). TNF-alpha is a cytokine that plays a central role in the regulation of the host immune and inflammatory response to infection. In the central nervous system, TNF-alpha is involved in induction of a fever response and triggers the release of other cytokines, and may also influence transport of compounds into the brain, leading to cerebrospinal fluid leukocytosis, increased protein influx, and lactate accumulation. Thalidomide has been shown to down-regulate the production of TNF-alpha. On the other hand, knowledge of the effects of thalidomide on granulocyte functions is limited. Thalidomide has been shown to attenuate neutrophil adhesion and chemotaxis. We present herein two cases of Streptococcus pneumoniae bacterial meningitis that developed soon after the initiation of thalidomide treatment, and discuss the effect of thalidomide on the immune system. Although, it is not clear whether thalidomide caused the development of the bacterial infections and meningitis, or what its pathogenetic mechanisms are, physicians should be alert for signs and symptoms of meningitis in patients with multiple myeloma who are treated with thalidomide, especially those in neutropenic states.

The efficacy of rituximab in patients with splenectomized refractory chronic idiopathic thrombocythopenic purpura.

The most difficult problem a physician encounters is the management of patients with idiopathic thrombocytopenic purpura (ITP), who has persistent severe thrombocytopenia after failure of initial treatment with glucocorticoids and splenectomy. Most of the patients refractory to corticosteroids and splenectomy will become refractory to other available agents, such as intravenous immunoglobulin (IVIg), danazol or chemotherapy. In this study, we investigated the effect of rituximab on 17 splenectomized refractory chronic ITP patients. Here, we showed that the anti-CD20 antibody, rituximab, induces a clinically significant response in severe chronic ITP patients, who are unresponsive to other therapeutic options. After sixth month, 10 out of 14 responders were still maintaining their durable and significant platelet responses (platelet counts >50 x 10(9)/l), without requirement to any other ITP medication. Therefore, we suggest that, rituximab is an effective treatment option in splenectomized refractory or relapsed ITP patients. Rituximab was well tolerated without severe side effects.

Thyroid and celiac diseases autoantibodies in patients with adult chronic idiopathic thrombocytopenic purpura.

The association of chronic idiopathic thrombocytopenic purpura (cITP) and thyroid autoimmune diseases (TAD) is a known but an uncommon condition. Celiac disease (CD), which is characterized by malabsorption and villous atrophy that occur as a consequence of the ingestion of wheat gluten may also be related to other autoimmune disorders. In this study, we investigated the prevalence of thyroid anti-microsomal (TAMA) and anti-thyroglobulin (TATA) auto antibodies, anti-gliadin (AGA) IgG, IgA, anti-endomisium (EMA) IgG and IgA antibodies in 74 patients with cITP and in 162 healthy controls. TATA positivity was found in 29, and TAMA positivity in 19 out of 74 patients; and in 16 and 18 out of 162 controls respectively (p < 0.0001 and p = 0.005, respectively). TAD was diagnosed in 29 of cITP patients. AGA IgG positivity was found in 17, and IgA was present in five out of 74 patients; and AGA IgG was found in 19, and IgA was detected in 4 out of 162 controls (p = 0.032 and p = 0.143, respectively). EMA IgG positivity was found in six out of 74 patients and in nine out of 162 control subjects (p = 0.566). EMA IgA positivity was found in two out of 74 patients and in one out of 162 controls (p = 0.232). We showed that the prevalence of TAD and related autoantibodies are higher in patients with cITP. We suggest that, patients with cITP should be followed up for development of TAD. In addition, all CD related auto antibodies were found to be more frequent in patients with cITP, but only the AGA IgG reached to the clinical significance. None of the CD related auto antibody positive patients developed clinically manifested CD. Large-scale designed studies are needed to clarify the long-term impact and importance of these CD related auto antibodies in patients with cITP.

Lamivudine for the prevention of hepatitis B virus reactivation in hepatitis-B surface antigen (HBSAG) seropositive cancer patients undergoing cytotoxic chemotherapy.

Hepatitis B virus (HBV) is one of the major causes of chronic liver disease worldwide. Cancer patients who are chronic carriers of HBV have a higher hepatic complication rate while receiving cytotoxic chemotherapy (CT) and this has mainly been attributed to HBV reactivation. In this study, cancer patients who have solid and hematological malignancies with chronic HBV infection received the antiviral agent lamivudine prior and during CT compared with historical control group who did not receive lamivudine. The objectives were to assess the efficacy of lamivudine in reducing the incidence of HBV reactivation, and diminishing morbidity and mortality during CT. Two groups were compared in this study. The prophylactic lamivudin group consisted of 37 patients who received prophylactic lamivudine treatment. The historical controls consisted of 50 consecutive patients who underwent CT without prophylactic lamivudine. They were followed up during and for 8 weeks after CT. The outcomes were compared for both groups. Of our control group (n= 50), 21 patients (42%) were established hepatitis. Twelve (24%) of them were evaluated as severe hepatitis. In the prophylactic lamivudine group severe hepatitis were observed only in 1 patient (2.7%) of 37 patients (p < 0.006). Comparison of the mean ALT values revealed significantly higher mean alanine aminotransferase (ALT) values in the control group than the prophylactic lamivudine group; 154:64 (p < 0.32). Our study suggests that prophylactic lamivudine significantly decreases the incidence of HBV reactivation and overall morbidity in cancer patients during and after immunosuppressive therapy. Further studies are needed to determine the most appropriate nucleoside or nucleotide analogue for antiviral prophylaxis during CT and the optimal duration of administration after completion of CT.

Familial Mediterranean fever gene mutations in the Southeastern region of Turkey and their phenotypical features.

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent inflammatory attacks of serosal membranes. Several studies have focused on the differences between frequency of the mutations and their phenotypical manifestations. The aim of this study was to evaluate whether or not this phenotypical variation is associated with the existence of particular mutations. Twelve MEFV (Mediterranean fever) gene mutations were investigated in 119 patients suffering from FMF. Heterozygote M694V (21/119), heterozygote E148Q (21/119), homozygote M694V (17/119) and heterozygote V726A (12/119) mutations were the most common mutations. Patients were grouped according to the presence of the M694V mutation: group I was M694V/M694V, group II was M694V/others, and group III was other/other. Mean severity scores for the groups were 13.94 +/- 4.10, 10.79 +/- 3.01 and 8.31 +/- 2.26, respectively. There were statistically significant differences between the mean severity scores of groups I and II (p = 0.029), groups I and III (p < 0.0001), and groups II and III (p < 0.0001). Diagnosis of amyloidosis was established in four (23%) patients of group I, and three (8%) patients of group II, but in none of the patients in group III. There was also a statistically significant difference between groups I and III (p = 0.046), but not between groups II and III (p = 0.083) and groups I and II (p = 0.317) in terms of amyloidosis development. In conclusion, we found a higher disease severity score and higher prevalence of amyloidosis in FMF patients who were M694V mutation carriers. Many ethnic groups live in Anatolia and more ethnic origin-based studies are needed to determine the real effect of these mutations on disease severity and amyloidosis.

Rhabdomyosarcoma presenting with destructive large lesion of the face.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents. RMS may be detected anywhere in the body, although the head and neck are the most involved areas. Prognostic factors of RMS include tumor status, primary tumor site, localization in the organ or tissue of origin, patient age and histopathological type. Alveolar histologic type is more aggressive than the other types and is seen in most patients with locally advanced and metastatic disease. A 27-year-old woman who was admitted to our clinic with a highly destructive lesion on her face is presented. She was diagnosed with alveolar rhabdomyosarcoma on histopathological examination.

Thrombophilia in young patients with acute myocardial infarction.

OBJECTIVE: To investigate the association of thrombophilia and coronary artery disease (CAD) in patients with myocardial infarction (MI). METHODS: Under the age of 45 years, 129 patients with MI and 107 control subjects were included into the study. Traditional risk factors of CAD and protein C, S, antithrombin III deficiencies, factor V Leiden (FV Leiden), prothrombin G20210A and methylenetetrahydrofolate reductase (MTHFR) C677T mutations were investigated. RESULTS: There were statistically significant differences in terms of obesity, smoking, triglyceride, total cholesterol, high-density lipoprotein, high-density lipoprotein, and very-low-density lipoprotein cholesterol, family history, hypertension, diabetes, and left ventricular hypertrophy between patients and controls. None of the patients and controls had protein C, protein S, and antithrombin III deficiencies. Ten patients (7.8%) and 4 controls (3.7%) had heterozygote FV Leiden mutation. Homozygous prothrombine G20210A gene mutation was detected in one patient (1.1%). Homozygous MTHFR C677T mutation was observed in 7.8% (patients) and in 6.5% (controls). Heterozygous MTHFR C677T mutation was detected 36.4% in patients and 31.7% in controls. The difference was not statistically significant in terms of carriage of thrombophilic mutations. CONCLUSION: We found that traditional risk factors increased the risk of CAD. Prothrombin G20210A, FV Leiden and MTHFR C677T mutations, protein C, S and AT-III deficiencies did not increase the risk of CAD in our young population.