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Molecular subtyping of Borrelia burgdorferi in erythema migrans and acrodermatitis chronica atrophicans.

Recently, three subtypes of Borrelia burgdorferi have been identified: Borrelia burgdorferi sensu stricto, Borrelia garinii, and the VS 461 group of Borrelia burgdorferi. These subtypes differ by nucleotide sequence variations within several Borrelia burgdorferi specific genes and most likely by their pathogenetic potential. To assess whether different subtypes of Borrelia burgdorferi might be associated with different cutaneous manifestations and clinical courses of Lyme disease, lesional skin biopsies from 35 patients with erythema migrans and 18 patients with acrodermatitis chronica atrophicans were analyzed. A Borrelia burgdorferi specific gene segment encoding a 26-kD protein with subtype specific nucleotide sequence variations was amplified by a nested polymerase chain reaction technique. For molecular subtyping, the products were transcribed into complementary RNA. Upon polyacrylamide gel electrophoresis, complementary RNA molecules separate into several metastable conformational forms resulting in patterns of bands highly specific for the nucleotide sequence of the transcribed molecules. In biopsy specimens of erythema migrans, the VS 461 subtype was detected in 28 of 35 and the Borrelia garinii subtype in six of 35 cases. In one of 35 cases of erythema migrans Borrelia burgdorferi sensu stricto as well as Borrelia garinii was detected. In contrast, in all 18 biopsies of acrodermatitis chronica atrophicans, only the VS 461 subtype was identified. This subtype is rarely found in the USA, where acrodermatitis chronica atrophicans is almost unknown. These data indicate that acrodermatitis chronica atrophicans might be closely associated with the VS 461 group of Borrelia burgdorferi.

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Abnormal immune responses during hypozincaemia in acrodermatitis enteropathica.

Immune responses were characterized in six patients with acrodermatitis enteropathica during a break in zinc supplementation and during resupplementation. During hypozincaemia the number of T-cells increased but the amount of B-cells and the responses of T- and B-lymphocytes to phytohaemagglutinin, concanavalin A-, pokeweed mitogen- and Staphylococcus aureus stimulations in vitro were subnormal. Cell counts and stimulation results both normalized when serum zinc values improved. One patient was anergic to tuberculin while showing signs of acrodermatitis enteropathica; she converted during supplementation whereas the others were continuously positive. Three females had antibodies against nuclear antigens and slightly elevated serum IgE concentrations; these values were not affected by the break in supplementation. Four females were continuously rheumatoid factor positive. Our findings suggest that zinc deficiency is closely associated with impaired immune responses in patients with acrodermatitis enteropathica, and laboratory markers of autoimmunity occur in a considerable number of the acrodermatitis enteropathica patients, irrespective of their zinc status.

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[Acrodermatitis enteropathica--zinc as a life-saving drug].

Formerly acrodermatitis enteropathica was treated with oxiquinoline without full control of the disease and with the danger of blindness. Moynahan has introduced zinc into the treatment with excellent results, based on the finding that acrodermatitis enteropathica is a zinc-deficiency disorder. Other authors and own observations have confirmed the findings of Moynahan. There are clinical, genetical, immunological and therapeutical parallels between the acrodermatitis enteropathica of man and the so-called hereditary parakeratosis of calves which also is a hereditary disturbance of zinc metabolism. The treatment of acrodermatitis enteropathica with zinc is furthermore a great success in the prevention of blindness, as zinc is not dangerous to the retina and the optic nerve.

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Rheumatic manifestations related to acrodermatitis chronica atrophicans. A review of four cases.

BACKGROUND: Acrodermatitis chronica atrophicans is a delayed manifestation of Lyme disease caused by a Borrelia burgdorferi subspecies, B. afzelii. Although rheumatic manifestations are rare, they can result in deformities of the fingers and toes if they are not treated promptly. METHODS: We report four cases of acrodermatitis chronica atrophicans seen over a 15-year period. RESULTS: Two patients had a noninflammatory unilateral knee effusion and one had swelling of the dorsum of one hand. Antimicrobial therapy was followed by a full recovery in the three patients who received an early diagnosis. The remaining patient, a 63-year-old woman, had swelling and dysesthesia in the fingers of both hands. She developed finger deformities over a period of two years. Although the swelling resolved under antimicrobial therapy, she had persistent reducible deformities of the fingers consistent with Jaccoud's arthropathy. CONCLUSION: The diagnosis of acrodermatitis chronica atrophicans rests on a history of a tick bite, a suggestive skin biopsy histology and a positive Western blot for B. afzelii. A positive response to antimicrobial therapy is also required. Acrodermatitis chronica atrophicans, a common condition in central and northern Europe, can cause joint manifestations and persistent finger deformities in the absence of early treatment.

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[PUVA-bath photochemotherapy in Hallopeau's acrodermatitis continua suppurativa].

A 73-year-old man presented with severe, relapsing acrodermatitis continua of Hallopeau, which had been resistant to prior local and systemic therapy for eight years. The patient was treated with selective hand PUVA-bath photochemotherapy. The cumulative dose of UVA used over 10 weeks of treatment was 54.6 J/cm2 on the palms and 26.8 J/cm2 on the dorsum of the hands. The single UVA doses ranged from 0.5 to 2.5 J/cm2 on the palms and 0.2 to 1.4 J/cm2 on the dorsum of the hands. After 16 treatment sessions, the acrodermatitis continua started to improve, and after 24 treatments, had cleared completely. In the four months following the PUVA therapy, there was no relapse. PUVA-bath photochemotherapy is an efficient therapeutic alternative in the treatment of acrodermatitis continua due to its clinical effectiveness and lack of any systemic side effects. It also possesses the advantage of allowing selective photosensitization of certain areas of the skin such as the hands.

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Expression pattern, genomic structure and evaluation of the human SLC30A4 gene as a candidate for acrodermatitis enteropathica.

Slc30a4 is the fourth and last identified member of a mammalian proteins family presumably involved in the cellular transport of zinc, solute carrier family 30. The murine homologue of the human SLC30A4 gene has previously been investigated and found responsible for the lm, a phenotype due to zinc deficiency. According to the strong homology between mouse and human SLC30A4 coding sequences, and to the very similar clinical features encountered in the murine lm and in human acrodermatitis enteropathica, SLC30A4 has appeared to us to be a good candidate for acrodermatitis enteropathica. Here we detail the genomic structure of human SLC30A4 together with its localization on chromosome 15q15-q21. We also report the mutational analysis of human SLC30A4 in ten families with acrodermatitis enteropathica, which enabled us to exclude this gene from any involvement in the disorder of the patients examined.

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Acrodermatitis continua of Hallopeau: treatment with etretinate and review of relapsing pustular eruptions of the hands and feet.

Acrodermatitis continua of Hallopeau is considered by many to be a variant of pustular psoriasis because of similar histologic features. Its clinical picture is unique and helps to distinguish acrodermatitis from pustular psoriasis. We present a patient with acrodermatitis continua of Hallopeau resistant to conventional therapy. We describe the beneficial effect of etretinate in this patient.

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Severe zinc deficiency presenting with acrodermatitis during hyperalimentation: diagnosis, pathogenesis, and treatment.

Seven patients developed severe zinc deficiency with acrodermatitis during hyperalimentation. Several of them had other problems such as diarrhea, poor wound healing and mental changes, which may also have been related to zinc deficiency. Three patients were on hyperalimentation for 2 weeks or less when skin lesions first developed, and most patients were receiving regular infusions of plasma. All patients responded to enteral administration of zinc. We conclude that: 1) severe zinc deficiency with acrodermatitis is not a rare complication of hyperalimentation; 2) even short-term hypralimentation may be complicated by severe zinc deficiency with acrodermatitis; 3) plasma is not an appropriate way to provide zinc supplementation; 4) if intravenous zinc preparations are not available, oral supplementation is usually effective; and 5) all patients undergoing hyperalimentation should receive zinc supplementation and have regular monitoring of their serum zinc level.

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Acrodermatitis enteropathica: zinc therapy and possible identification of a carrier state through multiple hair zinc analyses over three decades.

We report on the successful use of repeated hair analyses over three decades to monitor zinc and copper status in two siblings with Acrodermatitis enteropathica who were treated with oral zinc sulfate beginning in 1975. Furthermore, we report for the first time that analysis of zinc in hair over a 30-yr period allows for the identification of individuals who might be heterozygous carriers of this autosomal recessive disease and who, therefore, would be expected to have hair zinc levels intermediate between normal, healthy individuals and those with Acrodermatitis enteropathica. Zinc treatment of the two patients with Acrodermatitis enteropathica resulted in remission of the signs and symptoms of the disease within the first month of therapy. However, any short-term interruption (typically, 7-10 d) in oral zinc resulted in an almost immediate relapse, with the reappearance of the skin lesions. We also document the inverse relationship that exists between zinc and copper through analysis of these metals in the scalp hair from the two patients, thus providing a tool for ensuring adequate copper intake in patients taking relatively high doses of zinc over a long period.

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[Acrodermatitis enteropathica with mild course].

Acrodermatitis enteropathica is a disorder due to zinc deficiency in a human body. It is disease of autosomal recessive inheritance, that usually occurs in infants, typically develops in early months of life. Classical findings include acrodermatitis, diarrhea and alopecia. Natural course of disease is various from observed ones in 70 tumoral cases to subclinical cases without severe diarrhoea with improvement of post maturation period. We describe a 13-year-old girl with acrodermatitis enteropathica diagnosed after nine years from first symptoms.

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[Acrodermatitis enteropathica--a disturbance of zinc metabolism with zinc malabsorption (author's transl)].

The intestinal resorption of zinc using 65ZnCl2 was estimated in 3 patients with acrodermatitis enteropathica, 2 healthy controls, and 3 heterozygotes. After oral application of 65Zn the whole body activity was measured by a whole body counter for 34 days. The 65Zn resorption of the patients amounted to 16, 42 and 30% of the applied dose, whereas the resorption values of the heterozygotes and the controls were in the range of 58 and 77%. The elimination of 65Zn from the body amounted to about 0.7% of the applied dose with no difference between controls and patients with acrodermatitis enteropathica. Before therapy the serum-zinc levels of patients were markedly decreased. After oral application of high doses of zinc aspartate (2 times 400 mg/day) all clinical symptoms disappeared within a week. The results point at a causal connection between zinc and the pathogenesis of acrodermatitis enteropathica. Ultrastructural alterations of the Paneth cells of the intestines are also shown in this disease [12] as have also been seen in Paneth cells of zinc deficient rats [Beitr. Path. 145, 336 (1972)].

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Isolation of Borrelia burgdorferi sensu lato from a fibrous nodule in a patient with acrodermatitis chronica atrophicans.

A 66-year-old woman presented with a 2-year history of acrodermatitis chonica atrophicans of her left hand and associated fibrous nodules. In addition to skin changes she experienced profound fatigue, and pains and swelling of the left elbow and dorsum of the left hand. On clinical examination, typical livid-red discoloration of the skin distally from the left elbow was evident with atrophy on the dorsum of the hand. Nodules with diameters from 0.5 to 2 cm were present around the olecranon and along the ulnar region. The indirect immunofluorescent assay (IFA) without absorption in serum revealed negative borrelial IgM and positive IgG (1:512) antibody titres. Histological findings on tissue specimens were compatible with acrodermatitis chronica atrophicans and fibrous nodule tissue, respectively. Cultures in MKP medium of biopsy specimens from the involved skin and from one of the nodules were positive. Both isolates were identified as B. afzelii with concordant protein and plasmid profiles. The patient received a 3-week course of ceftriaxone (2 g daily, i.v.). Her condition progressively improved: pains and swelling vanished by the end of treatment, fibrous nodules diminished and skin lesions gradually began to fade. According to a MEDLINE literature search this is the first report of the isolation of B. burgdorferi sensu lato from a fibrous nodule in a patient with acrodermatitis chronica atrophicans.

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[Zinc treatment of acrodermatitis enteropathica (author's transl)].

Treatment of acrodermatitis enteropathica with zinc sulfate, first described by Moynahan and Barnes in 1973, has been widely accepted. We have treated a case of acrodermatitis enteropathica successfully with this drug. The 14-year old boy had to discontinue clioquinol because of a partial opticus atrophy. The skin lesions deteriorated acutely. Following zinc sulfate treatment the lesions rapidly disappeared and the general health of the patient greatly improved. Small doses of zinc sulfate are sufficient for maintenance therapy. The pathogenesis of acrodermatitis enteropathica is reviewed and the modes of action of zinc therapy are considered.

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Lymphoproliferative responses to Borrelia burgdorferi in patients with erythema migrans, acrodermatitis chronica atrophicans, lymphadenosis benigna cutis, and morphea.

BACKGROUND AND DESIGN: Specific humoral and cell-mediated immune responses play an important role in the pathogenesis of Lyme borreliosis. Several previous studies demonstrated that a specific cellular immune response to Borrelia burgdorferi can occur independently of a diagnostic humoral response. Little is known about T-cell reactivities against B burgdorferi in early and late cutaneous manifestations of Lyme borreliosis. We studied the lymphoproliferative response of peripheral blood mononuclear cells to B burgdorferi antigen from 99 patients (25 with erythema migrans, 16 with acrodermatitis chronica atrophicans, 13 with lymphadenosis benigna cutis, and 45 with localized scleroderma) and 21 control subjects. The results are expressed as a stimulation index (SI) (mean count per minute of triplicate cultures with stimulant divided by mean count per minute without stimulant). The serum samples from all patients and control subjects were tested for antibodies to B burgdorferi by indirect immunofluorescence assay. RESULTS: The 21 healthy seronegative controls had an SI of 3.3 +/- 2.0 (mean +/- SD). Compared with that of control subjects, the SIs were significantly elevated in patients with erythema migrans (9.8 +/- 9.1), acrodermatitis chronica atrophicans (11.8 +/- 8.2), and lymphadenosis benigna cutis (7.2 +/- 6.2). The 45 patients with localized scleroderma had elevated proliferative responses, with an SI of 6.5 +/- 7.3, but these responses did not significantly differ from those of controls. Elevated titers of antibodies to B burgdorferi were present in six (24%) of 25 patients with erythema migrans, five (38%) of 13 patients with lymphadenosis benigna cutis, and 13 (29%) of 45 patients with localized scleroderma. All 16 patients with acrodermatitis chronica atrophicans had markedly elevated antibody titers. CONCLUSIONS: Our findings show that a significant lymphoproliferative response to B burgdorferi occurs in the majority of patients with cutaneous manifestations of Lyme borreliosis. The lymphocyte proliferation assay may be of diagnostic value in patients in whom Lyme borreliosis is strongly clinically suspected and who have nondiagnostic levels of antibodies against B burgdorferi.

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Acrodermatitis chronica atrophicans in the United States: clinical and histopathologic features of six cases.

Acrodermatitis chronica atrophicans is a chronic cutaneous disease caused by the Lyme disease spirochete Borrelia burgdorferi. Acrodermatitis chronica atrophicans is endemic in some regions of Europe but is only rarely seen in the United States. This report describes the clinical and histopathologic findings in six cases of acrodermatitis chronica atrophicans seen at the Mayo Clinic between 1912 and 1961. Histologic differences between early and late phases of the disease were observed, and multisystemic symptoms consistent with chronic Lyme disease were documented in a subset of the patients. All five patients from whom biographical data were available were European immigrants. Our data suggest that some of the first patients with Lyme disease in the United States came to the Mayo Clinic earlier in this century.

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Acrodermatitis enteropathico. Abnormalities of fat metabolism and integumental ultrastructures in infants.

Acrodermatitis enteropathica is a rare disease of childhood, characterized by periorificial and perioral dermatitis, acrodermatitis, diarrhea, and alopecia. Two patients were successfully treated with diiodohydroxyquin (Diodoquin). Lipid concentrations disclosed abnormal distribution of fats that resembled those of less mature infants fed diets low in linoleic acid even though the patients were actually on diets with high linoleic acid levels. Fatty acid distribution showed increased levels of linoleic acid that correlated with clinical improvement in the patient who was more ill. Skin fatty acids showed decreased levels of linoleic acid. Electron micrographs and histochemical staining disclosed increased lipids droplets in epidermal cells. Linoleic acid and zinc may have a role in the origin of the disease, and measurement of both skin and serum linoleic acid is suggested in the evaluation of its progress.

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Acrodermatitis enteropathica. Corneal involvement with histochemical and electron micrographic studies.

A case of acrodermatitis enteropathica occurred with corneal changes consisting of linear subepithelial corneal opacities. From the results of histochemical and electronmicrographic studies on a biopsy specimen of the corneal lesion, no definite conclusion may be drawn as to whether the corneal changes are a manifestation of acrodermatitis enterophathica or a result of iodochlorhydroxyquin therapy.

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Oral treatment of acrodermatitis enteropathica with zinc sulfate.

In a 7-year-old boy with acrodermatitis enteropathica, oral administration of zinc sulfate brought about complete relief of symptoms and signs, with clearing of the skin lesions, arrest of diarrhea, and growth of new hair. Considering the dramatic results obtained, we believe that oral treatment with zinc sulfate is an innocuous, inexpensive, and very effective medication for acrodermatitis enteropathica, which can replace the previously used and toxic diiodohydroxyquin-like drugs.

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