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Biomedical subjects

J Kanitakis

Publications and source records attributed to J Kanitakis.

At least 109 records · Page 6Linked to original sources

The effect of anti-CD4 monoclonal antibody treatment on immunopathological changes in psoriatic skin.

Recent clinical studies which showed the therapeutic effect of cyclosporin A and of anti-CD4 MoAb emphasized the role of activated CD4+ T cells infiltrating the lesional skin in the pathogenesis of psoriasis. The aim of the present study was to analyze the mode of action of anti-CD4 MoAb in 3 psoriatic patients who experienced an anti-CD4 MoAb-induced clinical improvement maximal 3-4 weeks after the onset of an 8-day therapy. We evaluated the effect of anti-CD4 MoAb treatment on the phenotype of resident and passenger inflammatory skin cells in lesional skin samples. We observed a gradual improvement of 3 out of 4 histopathologic features including parakeratosis, papillomatosis and acanthosis. In the dermis there was no modification in the density of the dermal mononuclear cell infiltrate, which consisted mainly of CD3+, CD45RO+, TCR alpha beta+, CD11a+, HLA-DR+T cells with a CD4/CD8 cell ratio of 1.5/1. Therefore as previously observed for peripheral blood mononuclear cells, the number of CD4+ T cells infiltrating the dermis remained unaffected by the treatment. In contrast, CD4 MoAb treatment was associated with drastic changes in the epidermis. These included a decrease in both CD4+ and CD8+ epidermal T cell infiltrate, diminished numbers of ICAM-1+ and HLA-DR+ keratinocytes and restored numbers of CD1a+ epidermal Langerhans cells. We conclude from this study that clinical improvement of psoriasis by anti-CD4 MoAb therapy paralleled: (1) a decrease in epidermal T cells, and (2) a down-regulation of keratinocyte activation markers (ICAM-1 and HLA-DR). These results suggest that the observed changes are secondary to down-regulation of inflammatory cytokine production by T cells in situ.

Adult↗

Familial autoimmune enteropathy with circulating anti-bullous pemphigoid antibodies and chronic autoimmune hepatitis.

In a family of four children (two boys and two girls), the two brothers had severe, protracted watery diarrhea beginning at 2 and 3 weeks of life, respectively. Duodenal mucosa in both patients showed total villous atrophy and severe inflammatory infiltration of the entire bowel. The first patient also had lymphoid cell infiltration of the pancreas and died at 6 weeks of age. The second boy is alive at 2 years of age and is immunocompetent, but still receives total parenteral nutrition. Indirect immunofluorescence studies revealed circulating antibodies to enterocytes, smooth muscle, thyroid, and islet cells. Bullous pemphigoid antibodies (230 and 180 kd), specific for hemidesmosomal proteins and usually associated with a subepidermal blistering skin disease, were detected by direct and indirect immunofluorescence studies and by Western immunoblot. A diagnosis of autoimmune hepatitis was made, based on evidence of chronic active hepatitis and circulating anti-smooth muscle antibody. Immunosuppressive treatments induced partial clinical remission of the diarrhea but no resolution of the small bowel injury. At 16 months of age, remission of the diarrhea occurred, but persistent autoimmune hepatitis led us to maintain treatment with prednisone and azathioprine, and later with cyclosporine. In this child, as in other patients with autoimmune disease, the link between autoantibodies and organ damage remains uncertain but immunosuppressive treatment is indicated.

Autoantibodies↗

Pseudo oral hairy leukoplakia in a renal allograft recipient.

Oral hairy leukoplakia (OHL) is a disorder of the tongue associated with Epstein-Barr virus (EBV). OHL is seen mainly in HIV infection but is also rarely seen in the course of iatrogenic immunosuppression, especially in kidney transplantation; OHL is even more rarely seen in immunocompetent hosts. Lesions that clinically and histologically mimicked OHL but were not associated with EBV were recently characterized as pseudo hairy leukoplakia. We present such a case that occurred in a renal allograft recipient; light and electron microscopy, immunohistochemistry, and in situ hybridization were used to examine the patient for the presence of EBV and human papillomavirus. Two independent treatments with topical retinoid and oral amoxicillin resulted in complete remission. Pseudo hairy leukoplakia may correspond, at least in some cases, to the conditions known as leukoedema and white sponge nevus; the distinction of these diseases from OHL is of importance because OHL is a hallmark of severe immunosuppression.

Cytoplasm↗

Linear IgA bullous dermatosis with autoantibodies to a 290 kd antigen of anchoring fibrils.

We describe a patient with a papulovesicular eruption associated with scarring and severe mucosal lesions that led to blindness. Direct immunofluorescence showed linear IgA deposits at the dermoepidermal junction. Indirect immunofluorescence microscopy showed that the patient's serum reacted with the dermal side of salt-split skin. Direct immunoelectron microscopy showed the IgA deposits to be associated with anchoring fibrils, whereas with Western blot analysis the patient's serum reacted with a 290 kd dermal antigen. On the basis of these findings, we suggest that our case may represent a form of IgA-mediated epidermolysis bullosa acquisita.

Adult↗

Disseminated superficial porokeratosis in a patient with AIDS.

We report the case of a 50-year-old male homosexual suffering from AIDS, who developed diffuse annular hyperkeratotic lesions on the arms and legs. Histopathological examination revealed typical features of porokeratosis, which clinically was of the disseminated superficial type. Ultrastructural examination showed a paucity of keratohyalin granules and lamellar bodies. Immunohistochemical studies showed an almost complete absence of Langerhans cells in lesional epidermis. Involucrin and filaggrin expression were altered in areas of cornoid lamella formation, whereas basal keratinocytes in these areas expressed PCNA/cyclin and, to a lesser degree, p53 protein. Porokeratosis may affect immunocompetent patients, but has also been reported in the setting of immunosuppression following organ transplantation. As far as we are aware, the development of porokeratosis during the course of HIV infection has not been reported previously.

Acquired Immunodeficiency Syndrome↗

Linear IgA bullous dermatosis of childhood with autoantibodies to a 230 kDa epidermal antigen.

Linear IgA bullous dermatosis (LABD) is an autoimmune, subepidermal disease defined on the basis of direct immunofluorescence findings. However, more recent techniques used to study bullous dermatoses suggest that LABD may be heterogeneous. A patient with LABD of childhood (chronic benign disease of childhood, CBDC) was studied by indirect immunofluorescence on salt-split skin and by Western blot in an attempt to characterize the involved autoantigen. This young girl's periorificial (mouth, genitalia), erythematovesicular lesions were diagnosed initially as herpes simplex. Histologic examination revealed eosinophilic spongiosis, suggesting the diagnosis of an autoimmune blistering disease. Direct immunofluorescence showed an exclusive linear IgA deposit at the dermoepidermal junction. Indirect immunofluorescence revealed circulating IgA autoantibodies that reacted with the epidermal side of salt-split skin; these reacted by Western blot with a 230 kDa epidermal antigen, as in bullous pemphigoid. This case, fulfilling the diagnostic clinical and direct immunofluorescence criteria for LABD/CBDC, seems to represent IgA bullous pemphigoid. It further underscores the nosologic heterogeneity of LABD, which probably includes, apart from bullous pemphigoid, epidermolysis bullosa acquisita and cicatricial pemphigoid.

Autoantibodies↗

Epidermolysis bullosa simplex with mottled pigmentation. Case report and review of the literature.

Epidermolysis bullosa simplex with mottled pigmentation (EBS-MP) is a rare genodermatosis of which only 4 pedigrees have so far been reported. We present herein a new family with EBS-MP comprising a peculiar punctate digital keratoderma. The propositus was an 18-year-old patient who had suffered since birth from posttraumatic bullae, followed by mottled pigmentation, plantar keratosis, nail dystrophy and peculiar punctate keratoses of the fingers. Histology, immunofluorescence and electron microscopy of a bullous lesion showed an intraepidermal cleavage and an increased number of melanosomes within basal keratinocytes, dermal macrophages and Schwann cells. The precise genetic defect responsible for EBS-MP is not known but could be due to two distinct, closely linked mutations. The nosologic relationship between EBS-MP and other forms of EBS as well as cases of hereditary bullous poikilodermic acrokeratosis is discussed.

Adolescent↗

Immunohistopathological study of autoimmune pemphigus. Lack of strictly specific histological and indirect immunofluorescence criteria for paraneoplastic pemphigus.

Paraneoplastic pemphigus (PNP) is a form of pemphigus considered to bear characteristic immunohistopathological features (vacuolar-interface dermatitis, keratinocyte dyskeratosis and reactivity of patients' sera with transitional epithelia). The present study was undertaken in order to investigate whether these criteria are specific enough so as to allow the diagnosis of PNP in the absence of clinical data. A retrospective study of 66 biopsies of pemphigus revealed that one third of them comprised histological signs of PNP; one of the corresponding sera reacted with mouse bladder epithelium. However, no evidence of a neoplastic disease was present in any of the patients, and Western blotting further excluded the diagnosis of PNP. These results suggest that some of the features considered characteristic of PNP are not strictly specific for this variety of pemphigus; hence this diagnosis cannot be reliably established by histology or immunofluorescence but requires biochemical studies.

Acantholysis↗

[Pachydermoperiostosis. An ultrastructural study].

BACKGROUND: Pachydermoperiostosis (PDP) is a rare genetically determined disease belonging to the group of hypertrophic osteoarthropathies. Its aetiopathogenesis remains unclear. Most hypotheses favour an exogenous stimulation of fibroblasts. METHODS: A clinically typical patient with PDP was studied by electron microscopy with particular reference to the dermis and its cellular constituents. Fibroblasts from involved skin were cultured and studied in comparison with control cells. RESULTS: Remarkable modifications of the structure of the dermis were observed, encompassing irregular caliber of collagen fibres, extracellular deposits of microfibrils and of amorphous granular substance corresponding to the Alcian blue positive deposits seen by conventional histochemistry. The in vitro growth of fibroblasts was normal. CONCLUSION: Authors reviewed aetiopathogenic hypotheses. Our data suggest a genetically determined alteration of extracellular matrix production by fibroblasts as a possible explanation for the development of PDP.

Adult↗

[Xanthogranuloma and cutaneous mastocytosis in adults].

Xanthogranuloma (XG) is a rare disease in adults. The authors report a case of XG in an 20 years-old woman. This observation is particularly interesting: First by the pathology of the cutaneous lesion which showed a dermal infiltrate composed of histiocytes and a few foamy cells but without Touton giant cells. Second by is association with a mastocytosis which disappeared when XG appeared. These data led the authors to discuss the misleading histology pattern of XG and also the pathogenesis of XG. In our case, it would appeared as a benign reactive process against mastocytosis.

Adult↗

[Pemphigoid in children].

INTRODUCTION: Bullous pemphigoid is rare during the childhood. The authors report the 51st case. CASE REPORT: Jeremie, a seven-month-old baby, had atypical bullous lesions. Histological examination, direct and indirect immunofluorescence were in favor of bullous pemphigoid. COMMENTS: Clinical and biological features of bullous pemphigoid are similar in the adult and in the infant. First treatment is represented by corticosteroids. Evolution is generally very good.

Facial Dermatoses↗

[Acute exanthematous pustulosis during amoxapine treatment].

Toxidermia is a well-known complication of antidepressor therapy, often related to photosensitization. The authors report an original case of amoxapine-related acute generalized exanthematous pustulosis which regressed at drug withdrawal.

Amoxapine↗

Association of skin malignancies with various and multiple carcinogenic and noncarcinogenic human papillomaviruses in renal transplant recipients.

BACKGROUND: Organ transplant recipients receiving immunosuppressive treatment are prone to skin carcinomas on sun-exposed areas, and the frequency of such carcinomas in the long term reaches 40%. These carcinomas primarily are squamous cell carcinomas (SCC), which often are preceded by viral warts and premalignant keratoses. Human papillomaviruses (HPV) with other cocarcinogenic factors have been reported to play a role in the development of carcinomas in these patients. METHODS: Five hundred renal-graft recipients referred to our department were examined for the presence of warts, precancerous keratoses, Bowen disease, keratoacanthomas, and basal and squamous cell carcinomas. Adequate material for histologic and virologic examination was obtained from 24 patients. An in situ molecular hybridization technique was performed using biotinylated DNA probes for HPV types 1a, 2a, 5, 16, and 18 under stringent conditions. RESULTS: HPV DNA was detected in 44 of 86 specimens, including 14 of 17 warts, 4 of 17 premalignant keratoses, 1 of 4 Bowen disease lesions, 8 of 12 keratoacanthomas, 3 of 4 tumors in which distinction between keratoacanthomas and SCC was difficult, and 14 of 30 SCC. Twenty-six of 44 positive specimens contained several HPV types, whereas 30 specimens contained oncogenic types. Benign types 1 or 2 were detected alone in five SCC. HPV types 16 and 18 (usually detected in genital lesions) were found in 26 samples from sun-exposed areas. CONCLUSIONS: Our results show that oncogenic and benign HPV often are detected within premalignant keratoses and SCC in organ transplant recipients, which suggests that HPV may play a role in the development of cutaneous malignancies.

Adult↗

[Cutaneous metastases of internal cancers].

Cutaneous metastases from internal tumours are relatively rare, appearing in ca. 4.5 percent of the cases, but their recognition is important; indeed, even though they usually appear during a known neoplastic disease, they may be the presenting sign of a hitherto unknown tumour. They may also constitute the first manifestation of relapse of a tumour considered to be in complete remission. Cutaneous metastases generally manifest as solitary or multiple nodules devoid of specific clinical features, over the head, chest and abdominal wall. They are mainly due to cancers of mammary origin in women, or of pulmonary, renal and gastrointestinal origin in men. Any histological type may be encountered, with a predominance of adenocarcinomas. The histological aspect often does not allow recognition of the primary site, which can be identified in selected cases by immunohistochemical studies. Although long survivals have exceptionally been observed after the development of cutaneous metastases, their occurrence usually has an ominous prognostic significance and considerably reduces the chances for an efficient treatment.

Humans↗

A novel antigen of the dermal-epidermal junction defined by an anti-CD1b monoclonal antibody (NU-T2).

NU-T2 is a mouse monoclonal IgG1 antibody to the CD1b molecule, (cross-)reacting with an antigen of the dermal-epidermal junction (NU-T2 DEJ AG). Further immunohistochemical characterization of the NU-T2 DEJ AG showed it to display unique properties that differentiate it from other known antigens of the dermal-epidermal junction. Indeed, the NU-T2 DEJ AG is primate-specific and present only in epithelial basement membranes. In normal human skin it is expressed within the lowermost lamina lucida of the dermal-epidermal junction but not in the deep part of epidermal appendages nor in the deep part of epidermal appendages nor in the basement membrane of dermal vessels, smooth muscles or nerves. In diseases with intraepidermal or intradermal cleavage, NU-T2 reactivity was observed at the floor of the blister. In various skin specimens with a cleavage through the lamina lucida (NaCl--or dispase-split skin, bullous pemphigoid, junctional epidermolysis bullosa), NU-T2 immunoreactivity seemed reduced, being localized at the dermal side of the cleavage. These results suggest that the antigen recognized by NU-T2 is a novel component of the lamina lucida of the dermal-epidermal junction, that seems to be important for dermal-epidermal adhesion.

Adult↗

Ultrastructural study of chronic lesions of erythema elevatum diutinum: "extracellular cholesterosis" is a misnomer.

Erythema elevatum diutinum (EED) is a rare disease of unknown origin that belongs to the spectrum of leukocytoclastic vasculitis. Chronic lesions of EED contain lipid deposits, for which the term extracellular cholesterosis has been coined. We studied a typical case of EED with long-standing lesions. Findings of electron microscopic examination revealed a heavy, exclusively intracellular lipid deposition that consisted of lipid droplets, myelin figures, and rare cholesterol clefts within histiocytes but also within epidermal keratinocytes, mast cells, pericytes, and lymphocytes. These findings are in keeping with the results of previous ultrastructural studies and suggest that the term extracellular cholesterosis is a misnomer; intracellular lipidosis would more accurately describe the lipid deposition.

Chronic Disease↗

Electron-microscopic observation of a human epidermal Langerhans cell in mitosis.

Langerhans cells are dendritic cells of the epidermis originating from bone marrow precursors which may exceptionally undergo mitosis within the skin. We report herein an electron-microscopic observation of a dividing LC within a seemingly hyperproliferative human epidermis. This observation further underlines the self-reproducing capacity of LC in situ and suggests that LC may respond to the same mitogenic stimuli as keratinocytes.

Child↗