Dasatinib associated lymphadenopathy in a chronic myeloid leukemia patient: A case report.

RATIONALE: Dasatinib associated lymphadenopathy (DAL) is a rare adverse event in chronic myeloid leukemia patients (CML). A case of voluminous lymphadenopathy in the context of DAL is presented. PATIENT CONCERNS: A 40-year-old male patient was diagnosed with BCR-ABL1 positive chronic stage CML 2 years ago and achieved complete molecular response on nilotinib, which was switched to dasatinib due to nilotinib intolerance. After 5 months on dasatinib, the patient presented with a large mass in the axillary region. DIAGNOSIS: Common infectious and autoimmune etiologies of lymphadenopathy were ruled out. The positron emission tomography/computed tomography (PET/CT) demonstrated a hypermetabolic lymphadenopathy highly suspicious of lymphoma. The subsequent biopsy excluded lymphoma or extramedullary blastic transformation of CML and revealed reactive lymphadenopathy with mixed (cortical and paracortical) pattern. Clinical history and clinicopathological correlation suggested the diagnosis of DAL. INTERVENTION: Dasatinib was discontinued and the patient remained in close follow-up. TKI treatment with nilotinib was reinitiated. OUTCOMES: Lymphadenopathy resolved clinically at 4 weeks and normalization of PET/CT findings was documented at 9 weeks after cessation of the drug. TKI treatment with nilotinib was reinitiated with good tolerance. LESSONS: DAL may present with voluminous lymphadenopathy consistent with malignancy in clinical and imaging workup. We describe the spectrum of lesions associated with DAL and identify common features with drug-induced lymphadenopathy.

Systemic lupus erythematosus in a patient with multiple system atrophy: A case report.

RATIONALE: Multiple system atrophy is a late-onset rare neurodegenerative movement disorder which results in debilitating disease. Fever frequently ensues in the context of infections which can be associated with significant morbidity and mortality, but among alternative diagnostic possibilities neoplasms and autoimmune disorders should be considered. PATIENT CONCERNS: We describe a case of a prolonged febrile syndrome in a 55-year-old female patient with onset of multiple system atrophy two years before presentation. Patient history and symptoms were not contributive to guide the diagnostic work-up. DIAGNOSIS: Initial evaluation provided no specific findings. Repeat testing of auto-antibodies revealed positive antinuclear and anti-ds DNA antibodies coupled with low complement which in conjunction with renal biopsy substantiated the diagnosis of systemic lupus erythematosus flare. INTERVENTION: Pending the biopsy result, treatment with hydroxychloroquine and corticosteroids was initiated. Due to failure to achieve remission, azathioprine was added, but symptoms persisted. Following the diagnosis of lupus nephritis, azathioprine was discontinued and induction treatment with cyclophosphamide in accordance with the Euro-Lupus regimen was initiated and upon completion followed by maintenance therapy with mycophenolate mofetil. OUTCOMES: The patient achieved remission after cyclophosphamide was added to treatment with corticosteroids and has not experienced new flares during the next two years. The neurological syndrome has remained stable during this period. LESSONS: To our knowledge, we report the first case of concurrent systemic lupus erythematosus and multiple system atrophy. Prolonged fever presents unique challenges in patients with rare diseases.

Copper levels in patients with hematological malignancies.

BACKGROUND: Copper levels are elevated in cancer patients compared to normal subjects. However, few studies have investigated the relationship between copper and hematological malignancies. METHODS: 84 patients with hematological diseases were studied, along with 50 healthy individuals. Copper was measured by flame atomic absorption spectrometry. The patients were classified to 2 homogeneous groups, acute and chronic hematological neoplasms, respectively. For the patients with acute hematological malignancies, relapse and remission were investigated in relation to serum copper levels. For chronic hematological neoplasms, serum copper was connected either with stable or progressive disease. Zeta-chain-associated protein kinase 70 (ZAP70) and CD38 expression, along with the unmutated VH immunoglobulin genes (IgVH) status were also determined for the 22 chronic lymphocytic leukemia (CLL) patients. RESULTS: 54 patients with relapse or progressive disease had elevated copper levels (mean value 1.8 mg/l), whereas 30 patients either in remission or in stable disease had normal copper levels (mean value 1.01 mg/l) (normal range 0.8-1.3mg/l). CONCLUSION: Hence, our study indicates that serum elevated copper levels are associated with hematological malignancies either in relapse or in disease progression, whereas normal copper levels are linked with hematological neoplasms in remission or in stable disease. Furthermore, we report for the first time an association between high serum copper levels and several adverse prognostic markers in CLL, such as increased expression of ZAP70 and CD38, along with elevated percentage of unmutated IgVH.

Statins, bone formation and osteoporosis: hope or hype?

Osteoporosis is a major health problem affecting both men and women. Statins, besides their action as lipid-lowering agents, seem to have additional pleiotropic properties, among them a beneficial effect on bone mineral density. The entirety of experimental and the majority of clinical studies as well as the only relevant meta-analysis suggest that statins have an anabolic effect on bone metabolism. Statins, osteoporosis and adipogenesis share the same pathway, RANKL/OPG. It would appear that an imbalance in this pathway could be responsible for the manifestation of some metabolic disorders such as diabetes mellitus, atherogenesis, multiple myeloma, osteoporosis. Possibly in the future, drugs which can intervene in this biochemical and pathophysiological cascade, like statins, in a variety of doses, could be used for the management of ectopic ossification syndromes and other bone disorders, even as an additive treatment. Until then, further large longitudinal randomized controlled studies for each statin separately are required to confirm this hypothesis.

Aggressive systemic mastocytosis associated with mesangioproliferative glomerulonephritis.

BACKGROUND/AIMS/METHODS: Aggressive systemic mastocytosis (ASM) is a subtype of systemic mastocytosis, which comprises a heterogenous group of disorders characterized by infiltration of bone marrow, skin, liver, spleen, lymph nodes and gastrointestinal tract by neoplastic mast cells. There is lack of data on the association of ASM with renal involvement, as kidney is not among the known organs affected by ASM. RESULTS/CONCLUSIONS: To the best of our knowledge, this is the first case of ASM associated with mesangioproliferative glomerulonephritis and monoclonal gammopathy of undetermined significance, without the presence of nephrotic syndrome. The patient's clinical course and the intriguing family history, along with the treatment selection are described. Finally, the proposed possible pathophysiological mechanisms explaining the renal involvement of our patient are discussed.

Vitamins and stroke: the homocysteine hypothesis still in doubt.

During the last years, many epidemiologic studies have identified homocysteine as an independent risk factor for cardiovascular diseases like coronary events, stroke, and venous thromboembolism. Supplementation with oral folate and vitamins B6 and B12 (mainly folate) reduce plasma homocysteine levels to a significant degree. Recent clinical trials showed that vitamin supplementation leads to slower progression or even regression of atherosclerotic lesions in the carotid arteries, as confirmed by ultrasonographic measurement of carotid intima media thickness. However, the recent Vitamin Intervention for Stroke Prevention (VISP) study failed to show any clinical effect on stroke prevention. It is unclear if homocysteine-lowering therapy really has a role in the prevention of cardiovascular diseases. Large trials, which are already conducted, will probably give the definitive answer. In this review, we try to keep pace with the data that make the homocysteine hypothesis still doubtful.

Incidence and etiology of acute non-malignant upper gastrointestinal bleeding in northern Greece.

AIM: To evaluate the incidence and etiology of acute non-malignant upper gastrointestinal bleeding (ANMUGIB) in northern Greece due to increased use of non-steroidal anti-inflammatory drugs (NSAIDs), including low-dose aspirin (L-A), exposure and geographical variability of Helicobacter pylori (Hp) seroprevalence. METHODS: A retrospective study of 110 patients admitted for hematemesis or melena during a 6-month period. All patients had undergone a gastrointestinal (GI) endoscopy during hospitalization. The presence of Hp was identified by biopsies and a (13)C-urea breath test in the case of Hp(-) biopsy bleeding peptic ulcer (BPU). The activity of ANMUGIB was assessed according to Forrest's classification. Statistical analysis was made by the chi(2)-test and Yates' correction. RESULTS: Most patients were in the two medium age groups with no significant difference between them (P < 0.001). NSAID or L-A (100 mg/day) use was reported in 42.73% of patients in a ratio 1:1 (P > 0.1) and Hp infection was found in 29.09% of patients. BPU, with approximately two-thirds in the bulb, erosions and varices were the most frequent sources. Hp infection was found in 60.65% of BPU, 65.57% were related to NSAIDs or L-A and 8.19% were non-Hp non-NSAID/L-A BPU. Flat spots were most commonly found with a significant difference (P < 0.001) to other stigmata of recent bleeding, except for clean base. CONCLUSIONS: In northern Greece, persons aged over 40 years are prone to ANMUGIB with a non-significant relationship to males. Hp infection and medication use, such as NSAIDS and L-A, are deeply involved in its etiology. Non-Hp non-NSAID/L-A BPU are a small proportion. ANMUGIB seems to have a generally good prognosis.