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3.
Br J Dermatol ; 173(3): 792-6, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25913891

ABSTRACT

Cases of immunobullous skin disease associated with ulcerative colitis (UC) have been previously reported in the literature. There is no clear explanation for this association. In this series, we report six cases of immunobullous disease in patients with UC and discuss potential mechanisms of pathogenesis proposed to explain these concomitant diseases. The clinical presentation, immunopathology and treatment of six new cases are described and analysed. We report six patients, two with linear IgA bullous dermatosis (LABD), one with bullous pemphigoid (BP), one with mucous membrane pemphigoid (MMP) and two with IgA pemphigus. The patients' ages ranged from 33 to 66 years at the onset of their skin disease, and all but one case had a documented age of UC onset, confirmed with colonoscopy, prior to the development of skin disease. Direct immunofluorescence results in these patients demonstrated IgA basement membrane zone (BMZ) antibodies in the LABD cases, IgG antibodies at the BMZ in the BP and MMP cases, and IgA cell surface antibodies in the patients with IgA pemphigus. Additionally, indirect immunofluorescence was positive in one of the patients with LABD, the patient with BP and both of the patients with IgA pemphigus. The temporal association of UC and skin disease, in addition to the resolution of skin disease with total colectomy in one case, suggests colonic mucosal antigenic stimulation driving immune activation and leading to immunobullous skin disease.


Subject(s)
Colitis, Ulcerative/complications , Skin Diseases, Vesiculobullous/complications , Adult , Aged , Colitis, Ulcerative/immunology , Female , Humans , Immunoglobulin A/immunology , Male , Middle Aged , Skin Diseases, Vesiculobullous/immunology
4.
J Eur Acad Dermatol Venereol ; 25(9): 1061-7, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21175873

ABSTRACT

OBJECTIVE: To assess the efficacy and safety of topical pimecrolimus 1% cream in the treatment of oral erosive lichen planus. DESIGN: A 6-week randomized, double-blind, vehicle-controlled phase followed by a 6-week open-label phase. SETTING: Outpatients of the Department of Dermatology, University of Utah. PATIENTS: Twenty-one patients with oral erosive lichen planus were randomized and treated with either pimecrolimus 1% cream or vehicle cream. INTERVENTION: Pimecrolimus 1% cream, or its vehicle, were applied twice daily for 6 weeks to each side of the mouth with a 2×2 inch gauze pad folded in half and placed directly on the erosive lesion. MAIN OUTCOME MEASURES: Efficacy was based on clinical evaluation of Investigator's Global Assessment (IGA) of the overall severity of the disease, erythema, measurement of the size of any target erosion in millimetres, and assessment of spontaneous pain. Blood levels of pimecrolimus were monitored in all subjects on day 0 and repeated on day 7. RESULTS: Pimecrolimus 1% cream was superior to vehicle cream in reducing mean IGA, pain, and erosion size. For the vehicle group that entered the open-label phase, pimecrolimus 1% cream improved the mean IGA, pain, erosion size, and erythema. Pimecrolimus levels were detected in nine out of 10 of the pimecrolimus-treated subjects. These levels were consistently low. The pimecrolimus cream was well-tolerated. No clinically relevant, drug-related adverse events were reported. CONCLUSION: Pimecrolimus 1% cream was superior to vehicle in reducing pain, erythema, decreasing erosion size, and improving overall severity of disease when compared with vehicle treatment.


Subject(s)
Dermatologic Agents/therapeutic use , Lichen Planus, Oral/drug therapy , Tacrolimus/analogs & derivatives , Administration, Topical , Dermatologic Agents/administration & dosage , Dermatologic Agents/adverse effects , Double-Blind Method , Humans , Tacrolimus/administration & dosage , Tacrolimus/adverse effects , Tacrolimus/therapeutic use
5.
Br J Dermatol ; 159(1): 120-4, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18503599

ABSTRACT

BACKGROUND: Dermatitis herpetiformis (DH) is a papulovesicular eruption caused by ingestion of gluten. It is characterized by the deposition of IgA in the dermal papillae. IgA antibodies directed at tissue transglutaminase (TG2) are elevated in gluten-sensitive diseases including DH and coeliac disease (CD). More recently, antibodies directed at epidermal transglutaminase (TG3) were identified in patients with DH, and this may be the dominant autoantigen in this disease. OBJECTIVES: To measure IgA antibodies to TG3 and TG2 in patients with DH and CD, and control populations. METHODS: Serum IgA antibodies against TG2 and TG3 were measured from adults with DH, adults and children with CD, patients with psoriasis, adult Red Cross blood donors, and paediatric controls. RESULTS: Patients with DH and CD had elevated levels of IgA anti-TG2 antibodies compared with control populations. The levels in the patients with DH and adults with CD were similar. IgA anti-TG2 antibodies were higher in the children with CD compared with adults with DH and CD, and with control populations. Patients with DH and adults with CD had elevated levels of IgA anti-TG3 antibodies compared with children with CD and control populations. There was a trend towards higher levels in the patients with DH compared with adults with CD. CONCLUSIONS: IgA antibodies to TG3 are elevated in patients with DH and adults with CD. The progressive expansion of the epitope-binding profile of IgA antitransglutaminase antibodies in patients with CD may explain the development of DH in patients with undiagnosed CD during their adult life.


Subject(s)
Autoantigens/blood , Celiac Disease/enzymology , Dermatitis Herpetiformis/enzymology , Immunoglobulin A/blood , Transglutaminases/immunology , Adolescent , Adult , Aged , Child , Child, Preschool , Dermatitis Herpetiformis/immunology , Female , Humans , Infant , Male , Middle Aged , Transglutaminases/metabolism
6.
Genes Immun ; 8(2): 108-14, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17136122

ABSTRACT

Celiac disease (CD) is a common autoimmune disease caused by exposure to the protein gliadin in wheat, and related prolamins in barley and rye. The prevalence of the disease in the US is 1:133. The aim of this study was to identify non-human leukocyte antigen (HLA) loci that predispose to CD. A genome-wide search of 405 microsatellite markers was performed on DNA samples from 160 families with a minimum of two cases of CD. Multipoint, parametric and non-parametric linkage (NPL) analyses were performed. Locations on chromosomes 1q, 3q, 6p, 6q, 7q, 9q and 10q showed linkage statistics (NPL scores or heterogeneity logarithm of the odds (HLOD) scores) of approximately 2.0 or larger. The greatest evidence for linkage outside of chromosome 6 was on 7q and 9q. An NPL score of 2.60 occurred at position 151.0 on 7q and a HLOD score of 2.47 occurred at position 144.8 on 9q under a recessive model. As expected, there was highly significant linkage to the HLA region on 6p, with NPL and HLOD scores exceeding 5.50. In conclusion, this genome-wide linkage analysis represents one of the largest such studies of CD. The most promising region is a putative locus on 7q, a region reported independently in previous genome-wide searches.


Subject(s)
Celiac Disease/genetics , Chromosome Mapping , Chromosomes, Human/genetics , Genetic Predisposition to Disease , Major Histocompatibility Complex/genetics , Genomics , Humans , Lod Score , Microsatellite Repeats/genetics , North America
7.
BMC Med Genet ; 2: 12, 2001.
Article in English | MEDLINE | ID: mdl-11737870

ABSTRACT

BACKGROUND: Celiac disease has a strong genetic association with HLA. However, this association only explains approximately half of the sibling risk for celiac disease. Therefore, other genes must be involved in susceptibility to celiac disease. We tested for linkage to genes or loci that could play a role in pathogenesis of celiac disease. METHODS: DNA samples, from members of 62 families with a minimum of two cases of celiac disease, were genotyped at HLA and at 13 candidate gene regions, including CD4, CTLA4, four T-cell receptor regions, and 7 insulin-dependent diabetes regions. Two-point and multipoint heterogeneity LOD (HLOD) scores were examined. RESULTS: The highest two-point and multipoint HLOD scores were obtained in the HLA region, with a two-point HLOD of 3.1 and a multipoint HLOD of 5.0. For the candidate genes, we found no evidence for linkage. CONCLUSIONS: Our significant evidence of linkage to HLA replicates the known linkage and association of HLA with CD. In our families, likely candidate genes did not explain the susceptibility to celiac disease.

8.
J Immunol Methods ; 258(1-2): 65-71, 2001 Dec 01.
Article in English | MEDLINE | ID: mdl-11684124

ABSTRACT

We have developed a high throughput HLA typing methodology that is a modification of the standard sequence-specific primer method. This approach is distinct from other methods using an automated DNA analyzer, as more than one gene is typed in a single lane. We have optimized the method for use on an ABI 373 automated genotyping machine. Primers were designed to preferentially amplify DNA fragments of the generic allelic groups of the DQA1 and DQB1 loci. PCR products representing alleles at the DQA1 locus were amplified using a different fluorescent dye than the PCR products from the DQB1 locus. Only three PCR reactions are required for low resolution typing of DQA1 and DQB1. Use of different labeled primers enables genotyping for both loci in a single gel lane, allowing for 64 samples to be typed at low resolution for both DQA1 and DQB1 on a single gel. Automated allele assignments were determined based on DNA migration distance through a polyacrylamide gel using a standard genotype allele-calling program. Accuracy of this method is greater than 98% for both loci. The strategy described here may be adapted to include more loci or to produce higher resolution typing of alleles encoded by these loci. It can be readily optimized for use on other slab gel or capillary electrophoresis systems.


Subject(s)
HLA-DQ Antigens/genetics , Histocompatibility Testing/methods , Alleles , Base Sequence , DNA Primers/genetics , Genotype , HLA-DQ alpha-Chains , HLA-DQ beta-Chains , Humans , Polymerase Chain Reaction/methods
10.
Am J Med Genet ; 98(1): 70-4, 2001 Jan 01.
Article in English | MEDLINE | ID: mdl-11426458

ABSTRACT

Celiac disease is an autoimmune gastrointestinal disorder characterized by mucosal atrophy of the jejunum on exposure to gluten, a protein found in grains. The purpose of our study was to determine the prevalence of celiac disease in children with Downs syndrome in a U.S.-based Caucasian population. The 97 Downs syndrome children were screened for celiac disease using serum IgA-anti-endomysial antibody testing, which is highly specific and sensitive for the disorder. Children with titers greater than 1:5 (using the IgA endomysial antibody [EMA] test; EMA+) were considered affected. Ten children (10.3%) were EMA+. We examined their HLA DQA1 DQB1 genotype, karyotype, clinical characteristics, and the prevalence of celiac disease in their first-degree relatives. The nine available karyotypes were trisomy 21. Downs syndrome-specific mean height percentile was 64%+/-26% (range <5-99%) and weight percentile was 43%+/-28% (range 5-95%). Presence of diarrhea, constipation, vomiting, and abdominal pain was similar for children with and without celiac disease. Only bloating symptoms were significantly more frequent in those with celiac disease (EMA+). Seven of eight (88%) genotyped EMA+ children had the celiac disease-associated high-risk HLA DQA1*0501 DQB1*0201 genotype as compared with 13/ 80 (16%) of EMA- children. Five of 48 (10%) first-degree relatives of the celiac disease (EMA+) children were EMA+. In conclusion, celiac disease, as diagnosed by positive endomysial antibody tests, has an increased prevalence in children with Downs syndrome in the U.S. as compared with the general population (1/250). Clinical and growth characteristics do not distinguish between children with and without celiac disease. Based on these observations, it is recommended that children with Downs syndrome be screened for celiac disease.


Subject(s)
Celiac Disease/epidemiology , Down Syndrome/epidemiology , Adolescent , Body Weight , Celiac Disease/complications , Celiac Disease/diagnosis , Child , Child, Preschool , Down Syndrome/complications , Female , Gastrointestinal Diseases/etiology , Genotype , HLA-DQ Antigens , HLA-DQ alpha-Chains , HLA-DQ beta-Chains , Humans , Immunoglobulin A/blood , Karyotyping , Male , Prevalence , Seroepidemiologic Studies
11.
Am J Gastroenterol ; 96(6): 1927-9, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11419853

ABSTRACT

Dermatitis herpetiformis is associated with a gluten-sensitive enteropathy in >85% of cases. Both the skin lesions and the enteropathy respond to gluten restriction. Linear IgA bullous dermatosis has a much lower prevalence of histological small bowel abnormalities, and lesions are not known to respond to gluten restriction. We report a patient with linear IgA bullous dermatosis and gluten-sensitive enteropathy. This report addresses the issue of whether linear IgA bullous dermatosis can be associated with gluten-sensitive enteropathy. We evaluated the response to gluten restriction and normal diet by following the status of the patient's jejunal biopsies and skin lesions. The patient responded to gluten restriction, as shown by resolution of jejunal abnormalities and skin lesions and subsequently by recurrence of jejunal abnormalities and skin lesions with reinstitution of a gluten-containing diet. This report demonstrates that linear IgA bullous dermatosis can respond to gluten restriction if an underlying gluten-sensitive enteropathy is present.


Subject(s)
Celiac Disease/etiology , Food Hypersensitivity/complications , Glutens/adverse effects , Immunoglobulin A , Skin Diseases, Vesiculobullous/drug therapy , Adult , Celiac Disease/pathology , Female , Humans , Jejunum/pathology , Skin Diseases, Vesiculobullous/complications , Skin Diseases, Vesiculobullous/immunology
12.
J Cutan Med Surg ; 5(1): 33-6, 2001.
Article in English | MEDLINE | ID: mdl-11281432

ABSTRACT

BACKGROUND: Eosinophilic fasciitis is a rare, scleroderma-like disease that usually affects the extremities of young to middle-aged males. The disease may cause flexion contractures and limit joint mobility and is associated with peripheral eosinophilia. The fascia, by definition, is infiltrated with mononuclear cells and typically with eosinophils. Eosinophilic fasciitis may be separated from another sclerodermatous disorder, linear scleroderma, by its response to systemic corticosteroids. The etiology is unclear but eosinophilic fasciitis has numerous disease associations. However, it has not previously been associated with renal failure and hemodialysis. OBJECTIVE: This article reports a case of eosinophilic fasciitis occurring four weeks following the onset of hemodialysis. METHODS: The clinical and histologic features confirmed the diagnosis of eosinophilic fasciitis. He was treated with systemic corticosteroids with good response. CONCLUSION: This is the first reported patient who developed eosinophilic fasciitis in close temporal relationship with the start of hemodialysis. While eosinophilic fasciitis may be coincidental with a common disorder, namely, renal failure, it is interesting to note that hemodialysis patients often have immune-regulation abnormalities and peripheral eosinophilia.


Subject(s)
Eosinophilia/complications , Fasciitis/complications , Renal Dialysis , Renal Insufficiency/therapy , Aged , Eosinophilia/immunology , Fasciitis/immunology , Humans , Male , Renal Insufficiency/complications , Renal Insufficiency/immunology , Time Factors
13.
Am J Dermatopathol ; 23(1): 24-8, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11176048

ABSTRACT

Several reports have documented the coexistence of basal cell carcinoma (BCC) with other lesions, including melanoma. This study was performed to determine whether nests of BCC contain benign melanocytes and Langerhans [corrected] cells. Ten cases of BCC were investigated to determine whether benign melanocytes and Langerhans [corrected] cells populate tumor nests. The BCCs were stained with antibodies to cytokeratin AEI/AE3, S-100, HMB-45, Melan-A, and CD1a proteins. We report that all 10 BCCs were populated by dendritic melanocytes distributed at the periphery (5/10 cases) or evenly throughout tumor nests (5/10 cases). Clusters of melanocytes were not identified in any of the BCCs. A total of 9 of 10 tumors showed staining of dendritic Langerhans cells with CD1a. A total of 8 of 10 tumors stained with cytokeratin AEI/AE3; in 6 of the 8 tumors, the staining was focal. We compared these findings with a single example of a BCC and melanoma in situ (MIS) collision tumor in which the cytokeratin AE1/AE3-positive epithelial nests of BCC were populated by a high density of malignant melanocytes that stained with S-100 and HMB-45. Melanocytes were disposed singly and in clusters of two or more cells within BCC tumor nests. We conclude from this study that BCCs are regularly populated by benign melanocytes and Langerhans [corrected] cells. Furthermore, when BCC is infiltrated with malignant melanocytes of MIS, the melanocyte density is higher and clusters of melanocytes can be observed. The significance of these two findings is unclear, as additional cases of BCC MIS collision tumor need to be studied.


Subject(s)
Carcinoma, Basal Cell/pathology , Langerhans Cells/pathology , Melanocytes/pathology , Skin Neoplasms/pathology , Antigens, Neoplasm , Biomarkers, Tumor/metabolism , Carcinoma, Basal Cell/metabolism , Humans , Immunoenzyme Techniques , Keratins/metabolism , Langerhans Cells/metabolism , Melanocytes/metabolism , Melanoma/metabolism , Melanoma/secondary , Melanoma-Specific Antigens , Neoplasm Proteins/metabolism , Neoplasms, Multiple Primary/metabolism , Neoplasms, Multiple Primary/pathology , S100 Proteins/metabolism , Skin Neoplasms/metabolism
16.
J Pediatr Gastroenterol Nutr ; 31(1): 22-7, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10896066

ABSTRACT

BACKGROUND: Celiac disease is an autoimmune disorder of the small intestine characterized by intolerance to gluten. Traditionally, diagnosis is made by intestinal biopsy. Testing for immunoglobulin (Ig) A endomysial antibodies in the serum also is used for diagnosis. Biopsy and serology revert to normal with adherence to a gluten-free diet. Often, after an index case is diagnosed, siblings with symptoms adhere to a gluten-free diet without biopsy or serologic confirmation. More than 90% of patients with celiac disease have the human leukocyte antigen (HLA) DQA1*0501-DQB1*0201 genotype. Non-HLA genes also have been implicated. METHODS: One hundred ninety-five individuals with confirmed or suspected celiac disease were identified in 73 families affected by the disease. IgA endomysial antibody testing was performed for all symptomatic family members who did not have biopsy-confirmed diagnoses. DNA samples were genotyped at D6S276 and the HLA class II loci DQA and DQB. RESULTS: At the time sampling was begun in families, 88 of 177 (49.7%) individuals were self-diagnosed and adhering to a gluten-free diet. Ninety percent (91/101) of confirmed cases (biopsy or serology) had at least 1 copy of the DQA1*0501-DQB1*0201 genotype, whereas only 67% (46/69) of cases self-diagnosed (adherence to gluten-free diet without confirmation) had at least 1 copy. Of confirmed cases, 61% carried two copies of DQB*0201. It is estimated that the HLA association and other unlinked genes contribute approximately equally to the sibling risk of celiac disease. CONCLUSIONS: A dosage effect of DQB1*0201 may be associated with an increased risk of celiac disease. Self-diagnosis of celiac disease is as common as confirmed diagnosis in families in the United States. Diagnosis of celiac disease on the basis of clinical response to gluten restriction is inaccurate. With long-term adherence to a gluten-free diet, serologic test results are likely to be negative. Based on HLA genotype, approximately one third of self-diagnosed individuals are unlikely to have celiac disease. However, it is not possible to determine which individuals consuming a gluten-free diet have the disease. Therefore, before starting a gluten-free diet, serologic screening and biopsy confirmation are necessary.


Subject(s)
Celiac Disease/diagnosis , Dermatitis Herpetiformis/diagnosis , HLA Antigens/genetics , Biopsy , Celiac Disease/genetics , Dermatitis Herpetiformis/genetics , Enzyme-Linked Immunosorbent Assay , Female , Gene Dosage , Genotype , Glutens/adverse effects , Haplotypes , Humans , Immunoglobulin A/analysis , Jejunum/pathology , Male , Nuclear Family , Prevalence , Risk Factors , Sensitivity and Specificity
17.
Int J Dermatol ; 39(3): 230-5, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10759969

ABSTRACT

BACKGROUND: Bullous pemphigoid is an immunobullous disease affecting predominantly older patients. In severe cases, high-dose corticosteroids and/or other immunosuppressants are often needed long term to control the disease. These can be associated with serious side-effects in this patient population. Objective To evaluate the benefit of plasmapheresis as a steroid saving agent in a cohort of 10 patients. RESULTS: Plasmapheresis was effective as a steroid saving therapy. All patients went into remission with a lower daily dosage of oral prednisone at 3 and 6 months postplasmapheresis. Two patients had side-effects from therapy that, while significant, did not interfere with long-term improvement in their disease. Eight patients had circulating immunoglobulin G (IgG) antibodies reactive with bullous pemphigoid antigen 1, and three of these had circulating antibodies reactive with bullous pemphigoid antigen 2 on Western immunoblot. CONCLUSIONS: Plasmapheresis was an effective steroid sparing therapy in these patients. Due to its high cost and potential morbidity, plasmapheresis should not be recommended as routine therapy for bullous pemphigoid, but it is a useful adjunct in resistant cases.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Carrier Proteins , Cytoskeletal Proteins , Nerve Tissue Proteins , Non-Fibrillar Collagens , Pemphigoid, Bullous/therapy , Plasmapheresis , Prednisone/therapeutic use , Adult , Aged , Aged, 80 and over , Autoantigens/immunology , Azathioprine/therapeutic use , Collagen/immunology , Combined Modality Therapy , Cyclophosphamide/therapeutic use , Dose-Response Relationship, Drug , Drug Therapy, Combination , Dystonin , Evaluation Studies as Topic , Female , Humans , Immunoglobulin G/blood , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Pemphigoid, Bullous/pathology , Remission Induction , Severity of Illness Index , Time Factors , Treatment Outcome , Collagen Type XVII
18.
J Am Acad Dermatol ; 42(2 Pt 2): 381-3, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10640939

ABSTRACT

Henoch-Schönlein purpura is a systemic vasculitis of unknown cause. It is frequently triggered by a streptococcal upper respiratory tract infection. Other bacteria have been implicated as triggering agents. We report a recurring case of Henoch-Schönlein purpura in a patient with Pseudomonas pyelonephritis. The Henoch-Schönlein purpura remitted only when the infection was eradicated. Pseudomonas infection should be added to the list of bacteria that can trigger Henoch-Schönlein purpura.


Subject(s)
IgA Vasculitis/etiology , Pseudomonas Infections/complications , Pyelonephritis/complications , Adult , Bacteriuria/microbiology , Biopsy , Chronic Disease , Humans , IgA Vasculitis/microbiology , IgA Vasculitis/pathology , Leg , Male , Pseudomonas Infections/microbiology , Pseudomonas Infections/pathology , Pseudomonas aeruginosa/isolation & purification , Pyelonephritis/microbiology , Pyelonephritis/pathology , Recurrence , Skin/pathology
19.
Br J Dermatol ; 141(5): 859-62, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10583167

ABSTRACT

Henoch-Schönlein purpura (HSP) is characterized by palpable purpura predominantly involving the lower extremities. On direct immunofluorescence IgA can be seen deposited in the blood vessel walls of the superficial dermis. The subclass distribution of antibodies to this IgA was studied in the biopsies of 28 patients with HSP by direct immunofluorescence using anti-IgA1 and anti-IgA2 specific monoclonal antibodies. All 28 patients' biopsies demonstrated deposition of IgA1 while only one patient had IgA2 deposition. Positive and negative controls stained appropriately. This demonstrates that IgA1 is the dominant IgA subclass found in the skin in Henoch-Schönlein purpura.


Subject(s)
IgA Vasculitis/immunology , Immunoglobulin A/analysis , Skin Diseases, Vascular/immunology , Skin/blood supply , Capillaries/immunology , Fluorescent Antibody Technique, Direct , Humans
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