Colagenosis perforante reactiva: un efecto secundario infrecuente asociado al sorafenib / No disponible

No disponible

Reactive perforating collagenosis: a rare side effect associated with sorafenib.

We present the case of a patient with a debut of reactive perforating collagenosis associated with the use of Sorafenib for stage IV hepatocarcinoma, very successfully controlled with local corticotherapy and systemic antihistamines. This is an extremely rare side effect associated with this treatment, as only another eleven cases of acquired perforating dermatoses associated with Sorafenib or other multi-kinase inhibitors have been found in the medical literature. Given the unusual nature of this presentation, high clinical suspicion and a correct histopathological study are indispensable for its correct filiation and treatment.

Unusual eruption in association with sorafenib: a case of acquired perforating dermatosis, reactive perforating collagenosis type.

The term, acquired perforating dermatoses (APD), represents a group of skin conditions that develop in adulthood and are characterized by transepidermal elimination of dermal connective tissue. This appears clinically as a papulonodule with a keratotic core. Although APD is typically associated with diabetes mellitus, chronic renal failure, and several other conditions causing generalized pruritus, there have been reports in the literature describing an association of APD with select drugs including sorafenib. We present a case of acquired perforating dermatosis in a patient with HIV and hepatocellular carcinoma undergoing treatment with sorafenib.

Identification of gene signatures for prednisolone-induced metabolic dysfunction in collagen-induced arthritic mice.

BACKGROUND: Prednisolone is a potent anti-inflammatory glucocorticoid (GC) but chronic use is hampered by metabolic side effects. Little is known about the long-term effects of GCs on gene-expression in vivo during inflammation. AIM: Identify gene signatures underlying prednisolone-induced metabolic side effects in a complex in vivo inflammatory setting after long-term treatment. MATERIALS & METHODS: We performed whole-genome expression profiling in liver and muscle from arthritic and nonarthritic mice treated with several doses of prednisolone for 3 weeks and used text-mining to link gene signatures to metabolic pathways. RESULTS: Prednisolone-induced gene signatures were highly tissue specific. We identified a short-list of genes significantly affected by both prednisolone and inflammation in liver and involved in glucose and fatty acid metabolism. For several of these genes the association with GCs is novel. CONCLUSION: The identified gene signatures may provide useful starting points for the development of GCs with a better safety profile.

[Side effects of the HMG-CoA reductase inhibitors (statins). Lupus erythematosus induced by Atorvastatin therapy]. / Dzialania uboczne inhibitorów reduktazy HMG-co A (statyn). Indukowany przyjeciem atorvastatyny toczen rumieniowaty.

The paper describes the case of 56 years old woman admitted to the Toxicology Department because of skin lesions, joint and muscle pain and elevated activity of transaminases and creatine phosfokinase as well in biochemical analysis. The symptoms occurred after 6 days of the Atorvastatin therapy. The clinical picture indicated side effects of the hipolipemic therapy, but the presence of the skin lesions suggested drug induced collagenosis (lupus erythrematosus, dermatomyositis). Immunological studies confirmed association with antinuclear antibodies (ANA) and anti-Mi-2 autoantibodies in the serum. Immunosuppressive therapy was ordered with clinical and biochemical improvement.

Acquired perforating calcific collagenosis after topical calcium chloride exposure.

A 24-year-old healthy man presented with a 6-week history of numerous umbilicated coalescing erythematous papules with some scale and crust on his anterior medial thighs. The eruption began 1 to 2 weeks after he spilled calcium chloride rock salts on his pants while salting the sidewalk during a snow storm. The salts dissolved and remained in contact with his skin for at least 4 hours until he was able to change clothes. A skin biopsy shows thick and thin collagen fibers with partial calcification in the papillary and upper reticular dermis associated with a sparse infiltrate of neutrophils, lymphocytes and mononuclear histiocytes. There are foci of transepidermal elimination of calcified fibers with adjacent epidermal hyperplasia and ortho- and parakeratosis. Von Kossa stain highlights calcification of the fibers, and trichrome stain confirms the fibers are collagen. A Verhoeff-van Gieson stain shows no abnormality of elastic fibers. The patient was treated with topical betametasone diproprionate cream twice daily for 3 weeks, as well as a short course of oral levofloxacin and topical gentamicin cream. The lesions resolved over 3 weeks with residual scarring. We report a unique case of acquired perforating calcific collagenosis secondary to topical calcium chloride exposure.

Regression of central giant cell granuloma by a combination of imatinib and interferon: a case report.

Central giant cell granuloma is a benign lesion of the jaws which is sometimes aggressive locally. The most common treatment is curettage,which has a high recurrence rate, particularly in more aggressive lesions. Other treatments such as interferon (IFN) and calcitonin have been described. We report a patient with Stickler syndrome and an aggressive central giant cell granuloma in the mandible. Initial treatment with calcitonin was not successful. A combination of IFN and imatinib, given for 9 months, initiated regression of the lesion that continued after treatment had ceased.

Sirolimus-induced inflammatory papules with acquired reactive perforating collagenosis.

Sirolimus is an immunosuppressive macrolide with antineoplasic properties that is increasingly used in posttransplantation immunosuppression. The treatment is frequently associated with cutaneous side effects such as sirolimus-associated acneiform facial dermatitis, which has been observed in up to 50% of treated patients. We report a 51-year-old female with liver transplantation who developed inflammatory papules and nodules on the face and the upper chest 3 weeks after the initiation of sirolimus therapy. Sequential biopsies revealed lymphocytic infiltration of the dermis with a peculiar pattern of sebotropism, while older lesions showed acquired reactive perforating collagenosis. The lesions were responsive to hydroxychloroquine treatment despite continued sirolimus treatment.

Characterization of the cytokine network at a single cell level in mice with collagen-induced arthritis using a dual color ELISPOT assay.

Collagen-induced arthritis (CIA) in mice has been classified as a Thl-mediated disease. However, most evidence for this has been obtained by indirect experiments; for example, the administration of neutralizing anti-interferon-gamma (IFN-gamma) antibody reduced the severity of arthritis. To obtain direct evidence about the cytokine balance in CIA mice, we analyzed the cytokine-secreting cell in CIA mice at the single cell level using a dual color enzyme-linked immunospot (ELISPOT) assay, which enabled us to analyze interleukin-2 (IL-2)-secreting cells or IL-4-secreting cells or both simultaneously. Furthermore, to characterize the cytokine network in the pathogenesis of CIA, the frequency of the cells secreting IL-12, which induced the development of naive Th cells into Th1 cells, was analyzed. The results show that in the prearthritic phase, the number of IL-12-secreting cells in spleen and peritoneal exuded cells is increased, and Th1 cells in lymph node and spleen are dominant. In contrast, after the onset of clinical arthritis, the number of IL-12-secreting cells in spleen, lymph node, and peritoneal exuded cells is decreased, and there is a shift from a Thl-dominant to a Th2-dominant state in lymph node and spleen. The results indicated that the pathogenesis of CIA is associated with a disruption in the normal ratio of Th1/Th2 at cell level.

[Interferon therapy and autoimmunity]. / Interferontherapie und Autoimmunität.

The treatment of viral hepatitis or malignomas with interferon (IFN) can increase the incidence of autoimmune disease. This paper reviews published case and study reports. The incidence of overt autoimmune diseases under IFN treatment is about 3%. Autoantibodies can be detected in 23% of the patients. Autoimmune thyroid diseases are the most frequent ones, but nearly all autoimmune diseases can occur. Beside benign and reversible courses chronic developments and lethal outcomes are possible. Actual concepts concerning the pathogenesis of IFN-associated autoimmunity include induction of MHC and other molecules as well as the modulation of lymphocyte functions. Clinical and paraclinical controls are necessary under treatment with IFN and during follow-up.

Adverse effects of thyroid hormone preparations and antithyroid drugs.

Thyroid hormone preparations, especially thyroxine, are widely used either at replacement doses to correct hypothyroidism or at suppressive doses to abolish thyrotropin (thyroid-stimulating hormone) secretion in patients with differentiated thyroid carcinoma after total thyroidectomy or with diffuse/ nodular nontoxic goitre. In order to suppress thyrotropin secretion, it is necessary to administer slightly supraphysiological doses of thyroxine. Possible adverse effects of this therapy include cardiovascular changes (shortening of systolic time intervals, increased frequency of atrial premature beats and, possibly, left ventricular hypertrophy) and bone changes (reduced bone density and bone mass), but the risk of these adverse effects can be minimised by carefully monitoring serum free thyroxine and free liothyronine (triiodothyronine) measurements and adjusting the dosage accordingly. Thionamides [thiamazole (methimazole), carbimazole, propylthiouracil] are the most widely used antithyroid drugs. They are given for long periods of time and cause adverse effects in 3 to 5% of patients. In most cases, adverse effects are minor and transient (e.g. skin rash, itching, mild leucopenia). The most dangerous effect is agranulocytosis, which occurs in 0.1 to 0.5% of patients. This life-threatening condition can now be effectively treated by granulocyte colony-stimulating factor administration. Other major adverse effects (aplastic anaemia, thrombocytopenia, lupus erythematosus-like syndrome, vasculitis) are exceedingly rare.

[Perforating verruciform collagenoma, an exogenous inclusion skin disease? Apropos of a case induced by calcium chloride]. / Le collagénome perforant verruciforme, une dermatose par inclusion exogène? A propos d'un cas induit par le chlorure de calcium.

INTRODUCTION: Perforating verruciform collagenoma, first described in 1963, designates papular and keratotic post-trauma lesions which show an aspect of epidermal perforation microscopically with large fragments of collagen issuing through fistulous chimneys, more or less pycnotic polynuclears and squamating or necrotic epidermal cells. Three publications have presented this diagnosis. CASE REPORT: We observed a patient with multiple lesions with macroscopic and microscopic presentations suggestive of perforating verruciform collagenoma. The lesions appeared after scratches and inoculation with calcium chloride. DISCUSSION: This case is similar to those observed after intradermal inoculation of calcium salts. In the 4 previous cases, perforating verruciform collagenoma was associated with trauma allowing the intradermal penetration of a particular foreign material (glass wool, vegetable debris, drugs or intravenous injections, wound caused by a metallic garbage bin). The exceptional nature of perforating verruciform collagenoma in highly frequent skin wounds would suggest that a very particular post-trauma process is occurring caused by the introduction of an exogenous substance within the derma: calcium chloride in our case, a non-specific material in the four previous cases.