Diagnostic challenges in a patient with calciphylaxia - a case report.

Calciphylaxis is a condition with unclear etiopathogeny with vascular calcifications and thrombotic occlusion that lead to necrotic lesions. It is usually described in patients with end-stage renal disease (ESRD), but also in other conditions. The mortality rate is high, due to sepsis and internal organ failure. We present the case of a patient with multiple comorbidities (ESRD, diabetes, hypertension, Mönckeberg's sclerosis) with problems of differential diagnostic due to the necrotic lesions that mislead initially to systemic lupus erythematosus (SLE) with necrotizing vasculitis.

Stevens-Johnsons syndrome or drug-induced lupus - a clinical dilemma: A case report and review of the literature.

Tumor necrosis factor inhibitors are the first biological agents used in the treatment of rheumatoid arthritis (RA) to have yielded satisfactory results in terms of clinical improvement and radiologic progression, but they are also associated with the possibility of occurrence of a number of autoimmune systemic events [drug-induced lupus (DIL), vasculitis, sarcoidosis] and localized adverse events [uveitis, psoriasis, interstitial lung disease, erythema multiforme including the major form Stevens-Johnson syndrome (SJS)]. During treatment with TNF inhibitors, many patients develop positivity for antinuclear, antihistone and anti-double stranded DNA antibodies, though only a minority of patients will develop clinical manifestations and approximately less than 1% will fulfill the classification criteria for systemic lupus erythematosus. Mucocutaneous manifestations are the most frequent manifestations of DIL following treatment with TNF inhibitors, and can be severe and occasionally difficult to differentiate from erythema multiforme/SJS. Stopping the causative drug (the TNF inhibitor) and general supportive measures are usually sufficient in mild forms, but in moderate to severe forms, systemic glucocorticoids and sometimes immunosuppressive drugs are required. The present report presents the case of a patient with rheumatoid arthritis who developed severe recurrent cutaneous reactions and positive autoantibodies during TNF inhibitor treatment, with difficulties in differential diagnosis and treatment. A review of the literature is also presented.

Mutational status of KRAS and MMR genes in a series of colorectal carcinoma cases.

BACKGROUND: The KRAS gene mutation is the most common somatic change in colorectal carcinoma (CRC) and is predictive of resistance to anti-epidermal growth factor receptor (EGFR) therapy in the metastatic forms. Microsatellite instability (MSI), a mismatch repair (MMR) system defect, accounts for 15-20% of all CRCs, more frequent in early stages. CRCs with MSI present better prognosis, a distinct histopathological aspect and a different response to chemotherapy. Patients with both KRAS wild type and MSI have a reduced risk of dissemination and recurrence. MATERIALS AND METHODS: Our study included formalin-fixed paraffin-embedded tissue samples from 40 patients with metastatic CRCs, aged between 40 and 71 years old, gender (males/females) ratio 2.33:1. The MMR proteins were analyzed using an indirect bistadial immunohistochemical (IHC) technique with monoclonal antibodies. KRAS mutations were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: Of the 40 tumors analyzed, 40% presented KRAS mutations located in codon 12 or codon 13. IHC expression of MMR proteins revealed a microsatellite stable status in 35 cases, including 15 cases with mutated KRAS. MSI status was identified in five cases (four with KRAS wild type). All MSI tumors had a poorer histological differentiation and four cases revealed a mucinous phenotype. Eighty percent of the patients with MSI status were older women. CONCLUSIONS: Our study demonstrates a 20% frequency of mutated KRAS in MSI CRCs, the incidence of KRAS mutations being inversely correlated with MSI status in these tumors. MMR protein deficient CRCs tend to occur in older females, have a poorer differentiation and are frequently associated with KRAS wild type.

KRAS gene mutations - prognostic factor in colorectal cancer?

The colorectal cancer (CRC) modern therapy is using adjuvant and neoadjuvant companion therapeutic agents, part of them having an anti-angiogenic action. Their benefic effect can be annulated by some gene mutations, which are interfering in signal transduction pathways. One of the more frequent activating mutations is occurring in the KRAS gene. We assessed the KRAS mutations by two molecular methods, in a group of patients with a follow-up until 144 months, aiming to establish eventual correlations between the presence of mutations and the evolution of patients. We tried to appreciate the prognostic value of these mutations. A retrospective study was conducted on 74 patients treated by radical surgery; the surgical specimens were analyzed macroscopically and the histopathological type and degree were established. PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) and pyrosequencing were performed on paraffin-embedded tumor specimens. Statistical analysis showed significant differences in survival between patients with wild type gene and patients with mutation in codon 13; the same results were also obtained regarding TNM I, II stages or Dukes type A and B cases. However, for the patients in stage IV pTNM, the evolution was slightly better in association with a KRAS mutation than in wild type cases.

Association between primary Sjögren's syndrome and non-Hodgkin's lymphoma.

Sjögren's Syndrome (SS) is one of the most frequent autoimmune disorders, which affects approximately 1% of the population. It occurs in patients of all ages, but especially females during the fourth and fifth decades of life with a female/male ratio of 9:1. The main target of this disease are the exocrine glands that are infiltrated progressively by lymphocytes and finally destroyed, leading to decreased exocrine secretion. Thus primary SS is usually defined as xerophtalmia (dry eye) and xerostomia (dry mouth) accompanied in 60% of cases by parotid swelling [1]. The most serious complication of Sjögren's Syndrome is the high risk of the occurrence of non-Hodgkin's Lymphoma.