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J Kanitakis

Publications and source records attributed to J Kanitakis.

At least 19 recordsLinked to original sources

Composite tissue allograft extends a helping hand to transplant immunologists.

The first successful human hand transplantation, performed on September 1998, has translated the scope of 'composite tissue allotransplantation' from research concepts into clinical practice. Beyond microsurgical problems that have been overcome several years ago, the main obstacle that still prevents the generalization of composite tissue allotransplantation is immunologic. This review, which summarizes the evidence obtained both from experimental animal models and from the first recipients of a hand transplant, is focused on the two immunological characteristics of composite allografts that set them apart from other solid organ allografts: (i) they contain skin tissue that elicits a strong immune response; and (ii) they contain lymphoid tissues (such as bone marrow and lymph nodes) that have the potential both to attack the recipient, and also to down-modulate the host immune response and induce tolerance. While on one hand, the composite tissue allografts raise new challenges to transplant immunologists, on the other they provide answers to questions that have remained unresolved for a long time. In this sense, composite tissue allografts extend a helping hand to transplant immunologists.

Graft Survival↗

[Human herpesvirus 6 encephalitis in trimethoprim-sulfamethoxazole-induced hypersensitivity syndrome].

INTRODUCTION: Human herpesvirus 6 (HHV-6), the causative agent of the common exanthem subitum, is a known cause of central nervous system infection in immunocompromised patients. It has been suggested that HHV-6 participate in the development of drug-induced hypersensitivity syndrome. CASE REPORT: We reported a case of HHV-6 encephalitis associated with hypersensitivity syndrome induced by trimethoprim-sulfamethoxazole in a 72-year-old HIV-negative woman. DISCUSSION: Our case confirmed that reactivation of HHV-6 infection may contribute to the development of the hypersensitivity syndrome.

Aged↗

[Drug hypersensitivity syndrome associated with a primary HHV6 infection].

INTRODUCTION: Drug hypersensitivity syndrome is a severe life-threatening drug reaction. An association between this syndrome and HHV6 reactivation has been hypothesized. CASE-REPORT: A 45 year-old women was treated with sulfasalazine for polyarthralgia. One month after beginning the treatment, she developed a drug hypersensitivity syndrome with severe acute hepatic failure. HHV6 serology and serum PCR revealed a primary HHV6 infection. DISCUSSION: We report the second case of drug hypersensitivity syndrome associated with a primary HHV6 infection. An immunological disorder may explain such an association by increasing viral replication. Detection and titration of anti-HHV6 antibodies in each case of drug hypersensitivity syndrome should help to confirm this association and possibly modify treatment strategy.

Adrenal Cortex Hormones↗

[Lupus profundus and myelopathy].

BACKGROUND: We report a case of myelopathy during the course of lupus profundus that is unique to our knowledge. CASE-REPORT: A 29-year-old woman had lupus profundus since 1999, initially associated with thrombopenia (28,000 platelets/mm3) treated with corticosteroids for 6 months. Several nodular eruptions occurred from 1999 to 2004. Antinuclear antibodies were positive at 1/320 to 1/640 and complement C4 fraction was low. While being treated with hydroxychloroquine for a recent flare-up of nodular lesions of lupus profundus, she complained of paraesthesia of the abdominal wall and of the upper and lower limbs, suggestive of a medullary lesion. MRI disclosed an image of acute myelitis at the level of the second cervical vertebra. High doses of corticosteroids were promptly administered intravenously (methylprednisolone bolus) followed by oral prednisone and hydroxychloroquine. Six months later the patient was free of neurologic or cutaneous symptoms. DISCUSSION: In the literature, systemic signs are rarely associated with lupus profundus and myelitis has never been reported. Lupus myelitis is a vascular and/or demyelinating and usually segmental lesion of the spinal cord. Neurologic symptoms are those of acute rather than chronic or recurrent transverse myelitis. The prognosis is poor with frequent and severe functional sequelae. Treatment is mainly based on high-dose systemic corticotherapy alone or combined with cyclophosphamide. Our patient responded favourably to early methylprednisolone bolus followed by oral corticosteroids and antimalarial treatment. CONCLUSION: Lupus profundus is classically of benign course with only cutaneous involvement, but it may sometimes be a sign of systemic lupus and in rare cases may be associated with severe complications.

Acute Disease↗

Bilateral hand transplantation: six years after the first case.

In this study we present our experience concerning bilateral hand transplantation. Two cases were performed: the first in January 2000 and the second in April 2003. Both recipients received the same immunosuppressive treatment, which was similar to those used in solid organ transplantation, including tacrolimus, prednisone and mycophenolate mofetil while antithymocyte globulins were added for induction. Both recipients presented two episodes of acute rejection (maculopapular lesions) in the first 3 months after transplantation; however, these were easily reversed after a few days increasing oral steroid doses and using topical immunosuppressants. The first recipient presented hyperglycemia and serum sickness while the second recipient suffered a thrombosis of the right ulnar artery and an osteomyelitis of left ulna. All the complications were successfully treated. Functional Magnetic Resonance Imaging (fMRI) showed that cortical hand representation progressively shifted from the lateral to the medial region in the motor cortex. After 6 and 2 years respectively, they showed a relevant sensorimotor recovery particularly of sensibility and activity of intrinsic muscles. They were able to perform the majority of daily activities and to lead a normal social life. The first recipient has been working since 2003. They are both satisfied with their grafted hands.

Adolescent↗

[Kaposi's sarcoma and organ transplantation: 22 cases].

BACKGROUND: The discovery of the Human Herpes virus 8 (HHV8) improved our knowledge of the pathogenesis of Kaposi's sarcoma. After organ transplantation, Kaposi's sarcoma exhibits distinctive features compared with other forms of the disease. PATIENTS AND METHODS: We report 22 cases of post-transplant Kaposi's sarcoma (12 kidneys, 2 kidney-pancreas, 6 livers and 2 hearts). The aim of this retrospective study was to analyze clinical and virological characteristics in these transplant patients and to specify the frequency of HHV8 seroconversions in this population. RESULTS: Twenty-one patients showed cutaneous lesions and 9 had visceral involvement. HHV8 serology was positive in 16/20 patients at transplantation and in 21/22 cases at the time of Kaposi's sarcoma diagnosis. Most cases corresponded to viral reactivations whereas seroconversions occurred in 2 cases and may have been linked to viral transmission by the graft. Treatment led to recovery in 68p. 100 of the cases. Two heart-transplant patients died from their disease. We included in our series two cases of re-transplanted patients without recurrence of Kaposi's sarcoma and one case of familial Kaposi's sarcoma. DISCUSSION: Seroconversions after transplantation emphasize the interest of systematic screening of HHV8 serology in transplant recipients and their donors.

Adult↗

Cannabis arteritis.

The main causes of arteriopathy in young patients include drugs, metabolic diseases, pseudoxanthoma elasticum and Buerger's disease. Arteritis due to Cannabis indica was first reported in 1960, and the role of this drug as a risk factor for arteritis was confirmed in several subsequent publications. A 38-year-old smoker with no previous contributory medical history except for long-standing cannabis abuse developed a dry necrotic lesion of the left big toe. Imaging examinations revealed proximal arteriopathy of the lower limbs that predominated on the left side. He had no atherogenic or thrombogenic risk factors, and no signs of pseudoxanthoma elasticum were found. Remarkably, the development of arteritis paralleled cannabis abuse. The course was slowly favourable after weaning from the drug, vasodilator treatment and hyperbaric oxygen therapy. Despite some subtle clinical differences (more proximal than distal involvement), cannabis arteritis may be considered as a particular form of Buerger's disease, where cannabis, along with tobacco, seems to cause arterial lesions. Along with the noxious effects of cannabis on vessels, a role for contaminating arsenic is also possible. Cannabis arteritis is not widely known, but may prove not to be so rare if one considers consumption of cannabis besides that of tobacco.

Adult↗

Lupus erythematosus with leflunomide: induction or reactivation?

BACKGROUND: Leflunomide is a new oral disease modifying antirheumatic drug with a good safety profile. CASE REPORT: The first case of lupus erythematosus in a 58 year old white woman after administration of leflunomide for primary Sjögren's syndrome is reported. The relationship between induced lupus and leflunomide was confirmed by the resolution of the skin rash when the drug was stopped and its recurrence when it was reintroduced following a dose-response effect. DISCUSSION: Peripheral blood cells from this patient, from 15 patients with rheumatoid arthritis, and from healthy controls were used in a bioassay, which suggested that leflunomide affected the Th1/Th2 balance. Such a side effect might be related, in part, to the anti-tumour necrosis factor alpha activity of leflunomide.

Antirheumatic Agents↗

Capillary leak syndrome induced by acitretin.

The mucocutaneous side-effects of systemic retinoids are well known. We report a patient with diffuse oedema, which is a very rare side-effect of retinoids. The pathophysiology of this condition is poorly known because of the rarity of relevant observations, but apparently corresponds to capillary leak syndrome. The outcome is invariably favourable following withdrawal of the drug, which should be definitively contraindicated in the patient.

Acitretin↗

In vitro reconstructed mucosa-integrating Langerhans' cells.

All three-dimensional in vitro mucosal models constructed, thus far, have only been reconstituted by epithelial cells. We have developed a reconstructed oral and vaginal epithelium that integrates Langerhans' cells (LC), the dendritic cells (DC) of malpighian epithelia. The epithelium was composed of gingival or vaginal keratinocytes seeded on a de-epidermized dermis (DED) and grown in submerged culture for 2 weeks. LC precursors, obtained after differentiation of cord blood-derived CD34+ hematopoietic progenitor cells (CD34+HPC) by granulocyte macrophage-colony stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta) and Flt3-ligand (Flt3-L), were introduced after 6-8 days of culture into the reconstituted epithelium. The in vitro reconstituted mucosal epithelium formed a multilayered, well-differentiated epithelial structure, confirmed by the immunohistochemical expression of cytokeratins 4, 6, 10, 13, 14, 16 and involucrin. LC were identified in the basal and suprabasal epithelial layers by CD1a antigen, S100 protein and Langerin/CD207 expression, and by transmission electron microscopy. Type IV collagen was expressed at the chorio-epithelial junction, and most ultrastructural features of this junction were visualized by electron microscopy. This in vitro reconstructed gingiva or vagina integrating LC represents interesting models very similar to native tissues. Because LC play an important role in the mucosal immune system, our models could be useful for conducting studies on interactions with pathogenic agents (viruses, bacteria etc.), as well as in pharmacological, toxicological and clinical research.

Antigens, CD↗

Afferent and efferent phases of allergic contact dermatitis (ACD) can be induced after a single skin contact with haptens: evidence using a mouse model of primary ACD.

Allergic contact dermatitis is a T cell-mediated delayed type hypersensitivity reaction that occurs upon hapten challenge in sensitized individuals. The inflammatory response in classical allergic contact dermatitis requires both a sensitization phase and an elicitation phase responsible for the recruitment and activation of specific T cells at the site of hapten skin challenge. Conversely, previously unsensitized patients may develop a "primary allergic contact dermatitis" after the first skin contact with potent contact sensitizers leading to a skin inflammation with all the features of classical allergic contact dermatitis. In this study we used an experimental murine model, referred to as contact hypersensitivity, to study the pathophysiology of primary allergic contact dermatitis and its relationship to classical allergic contact dermatitis. We show that one epicutaneous application of a nonirritant dose of hapten (2,4-dini-trofluorobenzene, fluorescein isothiocyanate) was sufficient to induce an optimal allergic contact dermatitis reaction at the site of primary contact with the hapten without subsequent challenge. As in classical allergic contact dermatitis, the skin inflammation in primary allergic contact dermatitis was mediated by interferon-gamma producing, CD8+ effector T cells that were induced in the draining lymph nodes at day 5 postsensitization and downregulated by CD4+ T cells. Reverse transcription-polymerase chain reaction analysis revealed that the primary allergic contact dermatitis reaction was mediated by a recruitment of CD8+ T cells at the sensitization skin site at day 6 postsensitization. Analysis of the fate of the hapten fluorescein isothiocyanate applied once on the skin revealed its persistence in the epidermis for up to 14 d after skin painting. These results suggest that the development of primary allergic contact dermatitis (i.e., without secondary challenge) is associated with persistence of the hapten in the skin, which allows the recruitment and activation of CD8+ T cells at the site of the single hapten application.

Acute Disease↗

[Hypomelanosis of Ito in a girl with Trisomy 13 mosaicism: a cytogenetic study].

BACKGROUND: Hypomelanosis of Ito was first described by Ito in 1952 as incontinentia pigmenti achromians. The consistent feature of the disease is a characteristic cutaneous hypopigmentation area following the lines of Blaschko, but the clinical manifestations are varied and hypomelanosis of Ito is regarded as a neurocutaneous syndrome. Hypomelanosis of Ito is sporadic but is probably a non-specific expression of chromosomal mosaicism; we report a case with four clones. CASE REPORT: We report the case of a 26 year-old woman with neurocutaneous hypomelanosis of Ito and Trisomy 13 mosaicism. She also exhibited skeletal and ophthalmologic disorders. Immunohistology revealed a PS100 and Melan A decrease in hypopigmented skin. Cytogenetic study of normal and hypopigmented skin fibroblasts showed mosaicism with four clones. DISCUSSION: This is the third case of Trisomy 13 mosaicism associated with hypomelanosis of Ito, although other anomalies on chromosome 13 have been described. Happle published "phylloid" pigmented cases, which are mainly associated with Trisomy 13. This is the first observation of four-clone mosaicism and can be explained by successive mutations during embryogenesis. Anomalies on chromosomes 5,6 and 21 have never been described. The definition of hypomelanosis of Ito is not well established and the disease is presently included in a group of "pigmentary dysplasia" with genetic mosaicism.

Adult↗