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PubMed1992

[Cyclosporin A in the therapy of inflammatory dermatoses].

The experience reported in the literature with cyclosporin A (CyA) in the treatment of various inflammatory and autoimmune dermatological diseases is reviewed and compared with the authors' own experience of treating 36 patients presenting with psoriatic arthritis [8], generalized pustular psoriasis [2], palmoplantar pustular psoriasis [12], Behçet's disease [2], disseminated circumscribed scleroderma [2], acrodermatitis continua suppurativa [2], pemphigus vulgaris [1], lupus erythematosus [3], pyoderma gangrenosum [1], severe atopic eczema [2], and actinic reticuloid [1]. On the basis of the authors' own experience and the reported results, treatment with CyA appears to be primarily indicated in pyoderma gangrenosum, circumscribed scleroderma, psoriatic arthritis and acrodermatitis continua suppurativa. In diseases such as actinic reticuloid, Behçet's disease, localized and generalized pustular psoriasis, treatment with CyA leads to good results with an acceptable risk-benefit ratio. In our view, it is doubtful whether treatment with CyA alone is indicated in alopecia areata, lichen ruber, dermatomyositis, atopic eczema, systemic scleroderma, bullous diseases, and lupus erythematosus, and in the last two it should be given only in combination with systemic steroids. Literature reports provide no support for the use of CyA in ichthyosis vulgaris, pityriasis rubra pilaris, and cutaneous T-cell lymphomas. The risk-benefit ratio of CyA treatment should be carefully considered, especially in diseases that are not life-threatening.

Behcet Syndrome↗
PubMedDate not supplied

Dermatological manifestations of Lyme borreliosis.

Lyme borreliosis is a multisystem infectious disease caused by the tick-transmitted spirochete Borrelia burgdorferi sensu lato. About 80% of all Lyme borreliosis cases represent skin manifestations (dermatoborrelioses). The three characteristic dermatoborrelioses are erythema migrans, borrelial lymphocytoma, and acrodermatitis chronica atrophicans, which occur in different stages of the disease. Erythema migrans is the hallmark of early Lyme borreliosis, whereas acrodermatitis chronica atrophicans is the characteristic manifestation of late Lyme borreliosis. Several spirochetal factors (e.g. infection with different genospecies, co-infection with other tick-transmitted pathogens) as well as host factors (e.g. cytokine patterns at the site of infection) influence the course of the disease. Diagnosis in the early stage of Lyme borreliosis relies on the clinical picture, whereas serological, molecular, microbiological, and histopathological findings are important adjuncts in the diagnosis of later stages of the infection. Antibiotic treatment is necessary for all stages and manifestations of Lyme borreliosis. Doxycycline is the antibiotic of choice for most patients with dermatoborrelioses.

Animals↗
PubMed1990

Oral cyclosporine in the treatment of inflammatory and noninflammatory dermatoses. A clinical and immunopathologic analysis.

Cyclosporine is known to be effective in the treatment of psoriasis. In this study, we have used oral cyclosporine (6 mg/kg per day) given for 5 to 30 weeks to 24 patients for the treatment of 12 different dermatoses. Patients with the following diseases demonstrated a marked response or total clearing: 1 patient each with pyoderma gangrenosum, pityriasis lichenoides chronica, and psoriasis of the acrodermatitis continua of Hallopeau type. Moderate to marked response occurred in both patients with epidermolysis bullosa acquisita and the patient with hidradenitis suppurativa. Minimal to moderate responses were obtained in both patients with granuloma annulare, 1 of 2 with acrodermatitis continua of Hallopeau, both patients with Darier's disease, and 1 of 6 patients with vitiligo. Little or no response was noted in both patients with sarcoidosis, all 3 patients with pityriasis rubra pilaris, 5 of 6 patients with vitiligo, 1 patient with pemphigus foliaceous, and 1 with pemphigus vulgaris. Clinical side effects were mild and transient and included dysesthesia, fatigue, hypertrichosis, nausea, and flushing. The most frequent clinically significant abnormalities were hypertension and renal dysfunction, with all factors normalizing within 1 month of discontinuation of cyclosporine therapy.

Administration, Oral↗
PubMed1980

Nutritional modulation of immune responses.

Malnutrition has been linked in field studies with increased susceptibility to infection, often associated with severe marasmus or kwashiorkor. However, studies by Jose and colleagues revealed an apparent paradox: while B-cell immunity was decreased by chronic moderate malnutrition, several aspects of T-cell immunity were enhanced. In extensive experimental studies we have analyzed the effects of dietary restriction in immunologic function and development of disease. Our investigations may be grouped into three related areas. 1) Differential effects of protein or protein-calorie malnutrition on B-cell and T-cell immunity. While antibody-mediated immunity was impaired in animals moderately restricted with respect to protein or total calories, several T-cell functions were consistently enhanced in mice, rats, guinea pigs, and monkeys. 2) Influence of restricting a single nutritional element, the trace metal zinc, on immunologic function. Zinc deficiency produces progressive thymic involution and a progressive loss of T-cell immunity functions in mice and rats. While congenital failure to absorb this element normally is the single cause of hereditary acrodermatitis enteropathica, a frequently lethal disease both in humans and in cattle, acrodermatitis enteropathica has also been linked with common variable immunodeficiency disease, total parenteral alimentation with preparations lacking zinc, several forms of cancer, marasmus, and kwashiorkor. 3) Inhibition by dietary restriction of development of the diseases of aging. Disorganization of thymus-derived immunity, and development with aging of genetically determined diseases in several strains of mice, can be sharply curtailed or even prevented by reducing the intake of total calories or fat. Similarly, development of mammary cancer in C3H female mice is prevented by restricting dietary intake of fat.

Aging↗
PubMed1995

[Lyme borreliosis--diagnosis, clinical aspects and therapy of the cutaneous form].

Occurrence of Lyme borreliosis and namely its skin forms have a rising tendency. Thick population of ticks and their relatively high contamination with borrelia (app. 9% in Slovakia), increased presence of man in nature and frequent professional exposition create good conditions for the spreading of the disease. During the period of 20 months in 1993-1994 19 cases of borreliosis were recorded among 2,187 patients hospitalized at the Bratislava Dermatologic Clinic--17 cases of erythema chronicum migrans and two cases of acrodermatitis chronica atrophicans. All patients stated that they came into contact with ticks 24 hours--12 months prior to the origin of dermatologic alterations. 14 cases of erythema chronicum migrans being IFT examined by means of B. burgdorferi antigen included 10 patients who yielded the titre of antibodies higher than 1:256; 6 patients being examined by means of ELISA test included 2 positive findings. The IFT values varied also in cases of classical clinical picture of erythema chronicum migrans and a discrepancy was observed between IFT and ELISA results. Two cases of acrodermatitis chronica atrophica had positive serologic test. The serologic tests were performed also in 4 cases of scleroderma with positive results. Into their analysis the authors included also other studies on the basis of which they present schemes of diagnostic examination and therapeutic interventions in Lyme borreliosis. (Tab. 2, Ref. 4.)

Adolescent↗
PubMed1993

[Skin changes in patients with Lyme borreliosis].

In introduction some clinical characteristics of Erythema migrans, Borrelia lymphocytoma and acrodermatitis chronica atrophica has been described. The importance of atypical forms of Erythema migrans and the difficulties in differential diagnosis of cutaneous manifestation has been stressed. In a prospective, and partly retrospective investigation of 1292 persons with tick bites, signs of Lyme borreliosis have been found in 18.96%. Number of such persons seen in dermatology wards is rising, and 18.2% of these are children less than 15 years of age. Patients seen in dermatology are mostly women (56.5%:43.5%). Nearly half of the patients with Erythema migrans did not known that they had a tick bite (42.5%). Lyme borreliosis was manifested mainly as Erythema migrans, 89% of patients. Borrelia lymphocytoma was encountered in 2%, and Acrodermatitis chronica atrophicans in 0.4% of patients, significantly less than in other reports. Sclerotic skin lesions were found in 4.1% of patients, and some macular and urticarial lesions were recorded. An incubation period generally less than three weeks preceded to skin manifestations, but in some patients this period could not be recorded. Skin lesions were located on lower extremities in 50.4% of patients, trunk in 25.5%, and upper extremities in 10.5% of patients. In 87% of patients skin lesions lasted less than three weeks. Symptoms were present in 62% of patients. Seropositivity to Borrelia burgdorferi has been found in 10.2% of patients, mostly three weeks after the tick bite.

Adolescent↗
PubMed1997

[Apoptosis in the morphology of Lyme borreliosis].

BACKGROUND: Morphological, mainly ultrastructural changes in borreliosis has been the matter of contemporary interest indeed and it seems to be more and more clear that they are the product of an immunologic reaction. The aim of this study is to find out the epidermal changes of erythema migrans and acrodermatitis chronica on the ultrastructural level. METHODS AND RESULTS: There were 14 cases of erythema migrans and 5 acrodermatitis examined and many apoptotic keratinocytes, but also Langerhans cells and melanocytes were the dominant findings. Considering the very short time needed for apoptosis there is a good reason to take our findings as an important component of the borreliosis pathogenesis. CONCLUSIONS: The presence of many apoptotic cells in Lyme disease epidermis emphasises the importance of the immunology in the borreliosis pathogenesis. The striking number of apoptotic melanocytes suggests the higher affinity of the borrelia to the neuroectodermal tissue.

Apoptosis↗
PubMed1998

Zinc deficiency in exclusively breast-fed infants.

Zinc deficiency in breast-fed infants is an important disorder. Unlike acrodermatitis enteropathica, it is transient and stops when nursing ends. We report two cases of premature infants, breast-fed only, who showed skin lesions resembling acrodermatitis enteropathica. Results of laboratory investigations revealed a lowered zinc level in the infants' serum and in the mothers' milk and a normal level of zinc in the mothers' serum. After the infants were given zinc supplements and their diets diversified, the skin lesions regressed and their serum zinc levels became normal.

Adult↗
PubMed1984

Gianotti-Crosti syndrome. A review of ten cases not associated with hepatitis B.

Studies of data from ten cases of infantile acrodermatitis and from eight cases reported in the North American literature disclose distinctive papular dermatosis of the face and extremities, often related to virus infection. None of our eight patients who were tested had evidence of hepatitis B infections, although transaminase values were elevated in two. All five patients who were tested had lymphocytosis. Six patients had antecedent upper respiratory tract symptoms. Data from our cases and from the other previously reported cases indicate that the eruption is a virus-related response. Although the hepatitis virus has been the most frequently encountered causative agent to date, other viruses, including Epstein-Barr virus, coxsackievirus, and parainfluenza virus, may produce a similar cutaneous response.

Acrodermatitis↗
PubMed1999

Positive serology for Lyme disease borrelias in primary cutaneous B-cell lymphoma: a study in 22 patients; is it a fortuitous finding?

BACKGROUND: The historical association of acrodermatitis chronica atrophicans (ACA), now known to be a late manifestation of Lyme disease caused by Borrelia afzelii, with cutaneous lymphoma, and several small series of PCBCL with positive Lyme disease borrelial serology initiated a study of this association. Material and methods In the last 9 years, 30 patients with PCBCL have been observed and followed, 22 of them were tested for borrelial serology. The control group consisted of 85 patients with NHL (10 cutaneous T-cell, 25 extranodal B-cell non-PCBCL, 50 nodal B-cell), 30 patients with breast cancer and 60 blood donors. The screening tests were two different ELISA tests for B. burgdorferi sensu lato and sensu stricto, and reactive sera were further tested with the ELISA test for B. garinii, a Western blot (WB) test for Swiss Borrelia strains and a WB test for Bavarian Borrelia strains, since an immunoblot made with local strains was not available. Studies with a differential WB test for B. burgdorferi sensu stricto, B. garinii and B. afzelii was performed afterwards, as well as serological studies ruling out cross-reactions with Leptospiras and Treponema. RESULTS: Fifteen of 22 patients with PCBCL were positive on the screening tests, three of them falsely. Thus, the incidence of positive borrelial serology was 12/22 (55 per cent) in the PCBCL group. No positives were detected in the cutaneous T-cell lymphoma group; 2/25 patients (8 per cent) were positive in the extranodal B-cell NHL group (the localizations being vestibulum nasi and oral cavity), 2/50 (4 per cent) were positive in the nodal B-cell NHL group, 2/30 (7 per cent) in the breast cancer group and 2/60 (3 per cent) in the blood donor group. The cumulative incidence in the control groups was 8/175 (4,6 per cent). The incidence was significantly higher in PCBCL patients as compared to each of the control groups, p value ranging from 0.004 to <0.0001. Two positive patients had ACA, one arthritis. Borrelia afzelii was most often implied for positive serology in the differential WB. No cross-reactions with Treponema and the Leptospiras were documented. CONCLUSION: In conclusion there appears to be a clustering of positive serology for Lyme disease Borrelias in PCBCL patients possibly related to an ethiopathogenic relationship. Mechanisms of Borrelia escape from immunosurveillance mechanisms, persistence of both their mitogenic and antigenic stimuli for B-cells, and SALT formation may be involved in the pathogenesis of a subset of PCBCL.

Acrodermatitis↗
PubMed1980

Ultrastructural changes in the small intestine of zinc deficient rats.

In normal rats changes in the enterocytes that appear to be associated with physiological cell death were found. They were confined to the villous tip and included fragmentation of the microvilli and increased electron density of the cytoplasm with morphological alterations of the organelles. Acute severe zinc deficiency in young rats results in degenerative changes in the enterocytes and microvillous damage which is not confined to the villous tip. Increased numbers of apoptotic bodies as a result of cell death are found. The enterocyte lesions differed from cell death preceding normal desquamation. There were no significant changes in Paneth cell ultrastructure. These results were compared with the ultrastructural findings reported in patients with Acrodermatitis Enteropathica.

Acrodermatitis↗
PubMed1989

Peripheral nerve disorders in Lyme-Borreliosis. Nerve biopsy studies from eight cases.

Clinical, cerebrospinal fluid and nerve biopsy findings from eight patients with peripheral nervous system complications of Lyme-Borreliosis are reported. Five cases showed the typical features of the Garin-Bujadoux-Bannwarth syndrome (meningoradiculoneuritis), one patient had a multiple mononeuritis associated with acrodermatitis chronica atrophicans Herxheimer. Two cases could not be classified under these diagnostic categories. In all patients we observed a prompt relief of signs and symptoms after antibiotic treatment. Nerve biopsy studies showed gross infiltrations of epineurial vasa nervorum and small infiltrations around endoneurial capillaries. The infiltrations consisted of lymphocytes, histiocytes and plasma cells. We did not find necrotizing changes of the vessel walls, but thrombosis and recanalization was observed in some epineurial vessels. Seven biopsies showed a significant loss of myelinated axons due to axonal degeneration. Only in one biopsy did we observe segmental demyelination next to axonal degeneration. We conclude that the PNS complications of Lyme-Borreliosis in early and late stages of the disease are angiopathic due to vasculitis of the vasa nervorum and primarily caused by axonal degeneration.

Acrodermatitis↗
PubMed1980

Protracted diarrhoea: secondary monosaccharide malabsorption and zinc deficiency with cutaneous manifestations during total parenteral nutrition.

Protracted diarrhoea in early infancy gives rise to many diagnostic and therapeutic problems. Jejunal biopsy often reveals villous atrophy of varying degrees. Severe reduction of small intestinal absorptive area causes secondary monosaccharide malabsorption, as well as secondary disaccharide deficiency, consequences which are relevant in any attempts at oral feeding. Morphologic, metabolic, endocrinological and microbiological studies have to be undertaken in order to establish a definitive diagnosis in protracted diarrhoea, but these studies often fail to reveal the aetiology of the disease. Immunologic abnormalities like phagocyte dysfunction, thymic atrophy and hypoplasia of B-cell regions in lymph nodes might be secondary events, but some types of immunodeficiency are of primary importance in the development of protracted diarrhoea. Total parenteral nutrition in many cases has to be instituted, with all its implications and hazards: septicaemia is the most dangerous of these. Zinc deficiency and acrodermatitis enteropathica may occur during total parenteral nutrition, and zinc deficiency secondarily contributes to the symptoms of diarrhoea. Parenteral administration of zinc is able to overcome these effects.

Acrodermatitis↗
PubMed1977

Serum zinc concentration during childhood.

Serum zinc concentrations in subjects of different ages were estimated by neutron activation analysis to obtain reliable reference values for the diagnosis of primary or secondary zinc deficiency during childhood. In these healthy individuals a small age-dependent variation of the mean values was found. Serum zinc concentrations were lower in cord blood (mean value: 880 X 10(-9) g/ml) and in infant;s (mean value: 820 X 10(-9) g/ml) than in adults (mean value 1178 X 10(-9) g/ml). In comparison to these values, the serum zinc concentration in a patient with secondary zinc deficiency and 4 patients with acrodermatitis enteropathica was reduced to about 25% of normal.

Acrodermatitis↗
PubMed1979

[Zinc deficiency syndrome during long-term parenteral nutrition in a patient with Crohn's disease and cirrhosis of the liver. Casuistry and zinc-pharmacokinetic (author's transl)].

A 29 year old patient with Crohn's disease and posthepatitic HBsAg-positive cirrhosis developed zinc deficiency in the course of complete parenteral nutrition. Zinc deficiency was proven by a low plasma zinc level of 12 microgram/dl. The daily input of zinc was 0.5 mg as calculated from the zinc concentration of infusion solutions used in parenteral nutrition during 3 1/2 months of treatment. The clinical picutre was that of acrodermatitis enteropathica. Cirrhosis of the liver and Crohn's disease were contributory causes of zinc deficiency. 6 bolus injections of 12-36 mg of zinc (total amount 144 mg) were given during 13 days. The plasma zinc level increased to 60-80 microgram/dl. 52% of the total amount of zinc injected were excreted by urine. The plasma half-life times of zinc were independent from basic zinc concentrations and averaged 1.55 +/- 0.22 h. It is concluded that severe signs of zinc deficiency will develop during parenteral nutrition in the presence of conditions leading to a negative zinc balance. In the case of long-term complete parenteral nutrition zinc should be substituted from the beginning of the treatment on.

Acrodermatitis↗
PubMedDate not supplied

Serological diagnosis of erythema migrans disease and related disorders.

An indirect immunofluorescence technique for the determination of antibodies against ixodid tick spirochetes is described. Differences in the reactivity between Ixodes ricinus spirochete and Ixodes dammini spirochete antigens were not observed. Cross-reacting antibodies against Treponema pallidum and Treponema phagedenis can be eliminated by quantitative absorption with T. phagedenis. Cross-reactions with leptospira were not observed by immunofluorescence. In the IgM test, false negative reactions caused by high-titered specific IgG antibodies or false positive reactions caused by rheumatoid factor occur. This can be avoided by testing the IgM fraction (19S-IgM-test) or using sera previously treated with anti-IgG serum. Significantly elevated antibody titers against ixodid tick spirochetes were observed in 45% of 44 cases with erythema migrans disease, in 72% of 29 cases of lymphocytic meningoradiculitis, in all of nine patients with acrodermatitis chronica atrophicans and in all of four investigated patients with lymphocytoma (lymphadenosis benigna cutis).

Acrodermatitis↗
PubMed1990

Comparison of flagellum and sonicate antigens for serological diagnosis of Lyme borreliosis.

A sonicate antigen and two concentrations of a purified flagellum antigen of Borrelia burgdorferi were compared for serological diagnosis of Lyme borreliosis by an enzyme immunoassay (EIA). Generally, the higher concentration of flagellum antigen was found to be superior to the lower concentration, which was diluted eight times compared to the higher concentration. The diagnostic sensitivity for IgG antibody detection increased from 13% in the sonicate EIA to 31% in the best flagellum EIA assay (p = 0.01) in sera from patients with erythema migrans (n = 70), and from 34% to 55% (p = 0.01) in sera from patients with neuroborreliosis (n = 77). However, the sensitivity for IgG in sera from patients with acrodermatitis chronica atrophicans (n = 20) was high in both assays: 90% in the sonicate EIA compared to 95% in the flagellum EIA. Regarding IgM, there was no significant difference between the sensitivity of the assays in sera from any of the patient groups. The sensitivity values for IgM and IgG in cerebrospinal fluid (CSF) from patients with neuroborreliosis were also without significant differences. Sera and CSF from patients with meningitis/encephalitis of non-Borrelia etiology (n = 35), multiple sclerosis (n = 9) or syphilis (n = 24), served as controls. The flagellum EIA showed a significantly improved specificity for IgG in CSF from controls with syphilis (p less than 0.01). It is concluded that purified Borrelia burgdorferi flagellum antigen is superior to a sonicate antigen, especially for serodiagnosis of the early stages of Lyme borreliosis.

Acrodermatitis↗
PubMed1999

Partial characterization of a human zinc-deficiency syndrome by differential display.

The effect of the acrodermatitis enteropathica mutation (AE) on gene expression was investigated using differential display. Two differentially expressed cDNAs were partially characterized. The NA8 cDNA (HT11A anchor and HAP 8 random primer pair) was expressed in greater quantity in normal fibroblasts, was 249 bp, and hybridized to three mRNA species (2 kb, 1 kb, 0.8 kb). Northern blot analysis indicated that the relative amounts of the AE mRNA species were reduced by 73%, 75%, and 52%, respectively. The cDNA sequence exhibited 92-93% homology to the human cytochrome oxidase subunit II, as analyzed through the GenBank database. The AEG4 cDNA species (HT11G anchor and HAP 4 random, primer pair) was expressed in greater quantity in AE fibroblasts, was 197 bp, and hybridized to two mRNA species (9 kb, 4 kb). Northern blot analysis indicated that the 9-kb mRNA species was present equally in AE and normal cells, but the 4-kb mRNA species was only present in the AE fibroblasts. The cDNA sequence exhibited 92% homology to LINE1 human retrotransposons, as analyzed through the GenBank database. The functional relationship between the mutation and the reduced expression of cytochrome oxidase subunit II is unknown at this time and needs to be addressed. The increased expression of the LINE1 element in AE fibroblasts may be indicative of an insertion mutation affecting the mRNA of a protein involved in zinc transport, a prospect which requires further investigation.

Acrodermatitis↗