ABSTRACT
BACKGROUND: Chronic spontaneous urticaria (CSU) is defined as symptoms of urticaria persisting for 6 weeks or more without obvious cause. Autologous serum skin test (ASST) positivity in patients with CSU is considered to be associated with autoimmune urticaria (AIU). METHODS: In this retrospective study we retrieved the medical records of 1,073 urticaria patients seen at the Department of Dermatology and Allergology of Szeged University between January 2005 and February 2014. Forty-two patients (36 female and 6 male) met the study criteria by having CSU and giving positive results in the ASST. Our aim was to assess the clinical efficacy and safety of low-dose oral prednisolone therapy administered to patients with antihistamine-refractory ASST-positive CSU for a few months. Patients were given an initial dose (40 mg/day) of prednisolone until the complete resolution of the symptoms, usually 7-10 days, and then the dose was gradually decreased, as in other autoimmune diseases. RESULTS: Prednisolone therapy lasted for an average of 3.6 months and a complete long-lasting response was achieved in 35 of 42 AIU patients (83.3%). The follow-up period was at least 36 months (3 years) for each AIU patient; the longest follow-up time was 139 months (11.5 years). None of the patients reported any considerable side effects. CONCLUSION: Based on our results, we suggest that the use of this treatment could be an alternative for the treatment of AIU. Our present results also highlight the need for other therapies in a small percentage of AIU patients. Our results suggest that AIU represents a transient autoimmunity that can be successfully treated with low-dose steroid therapy administered for a few months.
Subject(s)
Anti-Inflammatory Agents/administration & dosage , Autoimmune Diseases/drug therapy , Prednisolone/administration & dosage , Urticaria/drug therapy , Adult , Aged , Aged, 80 and over , Anti-Inflammatory Agents/adverse effects , Chronic Disease , Female , Humans , Male , Middle Aged , Prednisolone/adverse effects , Retrospective Studies , Treatment OutcomeABSTRACT
The authors present their experience related to the diagnosis, treatment, and followup of 431 patients with bullous pemphigoid, 14 patients with juvenile bullous pemphigoid, and 273 patients with pemphigus. The detection of autoantibodies plays an outstanding role in the diagnosis and differential diagnosis. Paraneoplastic pemphigoid is suggested to be a distinct entity from the group of bullous pemphigoid in view of the linear C3 deposits along the basement membrane of the perilesional skin and the "ladder" configuration of autoantibodies demonstrated by western blot analysis. It is proposed that IgA pemphigoid should be differentiated from the linear IgA dermatoses. Immunosuppressive therapy is recommended in which the maintenance dose of corticosteroid is administered every second day, thereby reducing the side effects of the corticosteroids. Following the detection of IgA antibodies (IgA pemphigoid, linear IgA bullous dermatosis, and IgA pemphigus), diamino diphenyl sulfone (dapsone) therapy is preferred alone or in combination. The clinical relevance of autoantibodies in patients with autoimmune bullous dermatosis is stressed.
Subject(s)
Autoantibodies/immunology , Autoimmune Diseases/immunology , Immunoglobulin A/immunology , Skin Diseases, Vesiculobullous/immunology , Animals , HumansABSTRACT
Sortilin, a member of the family of Vps10p domain receptors, has been shown to be able to bind the precursor peptide of nerve growth factor (proNGF). ProNGF interacts with sortilin and the p75(NTR) receptor on the cell surface to form a molecular complex capable of activating an apoptotic cascade. Keratinocytes can secrete proNGF and they have p75(NTR) on their surface. The expression of sortilin in normal human keratinocytes has not yet been clearly shown. In this study, we show that keratinocytes express sortilin mRNA, and the presence of sortilin protein is shown in cultured keratinocytes and in normal human skin. We have also shown that the cutaneous neuropeptides substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide, and galanin are able to reduce the expression of sortilin mRNA and sortilin protein in cultured human keratinocytes. In addition, each of the analyzed neuropeptides has the ability to arrest the proNGF-induced apoptosis of human keratinocytes. These results suggest that all the participants in the NGF/proNGF pathway are present in the keratinocytes, and cutaneous neuropeptides can modulate their expressions and actions. The NGF/proNGF balance and its regulation by neuropeptides may have an important role in skin homeostasis.
Subject(s)
Adaptor Proteins, Vesicular Transport/genetics , Keratinocytes/physiology , Neuropeptides/metabolism , Neuropeptides/pharmacology , Adaptor Proteins, Vesicular Transport/metabolism , Adult , Apoptosis/drug effects , Apoptosis/physiology , Calcitonin Gene-Related Peptide/metabolism , Calcitonin Gene-Related Peptide/pharmacology , Cells, Cultured , Female , Galanin/metabolism , Galanin/pharmacology , Gene Expression/drug effects , Gene Expression/physiology , Humans , Keratinocytes/cytology , Nerve Growth Factor/metabolism , Nerve Growth Factor/pharmacology , Nerve Tissue Proteins/metabolism , Protein Precursors/metabolism , Protein Precursors/pharmacology , Receptors, Nerve Growth Factor/metabolism , Skin/cytology , Substance P/metabolism , Substance P/pharmacology , Vasoactive Intestinal Peptide/metabolism , Vasoactive Intestinal Peptide/pharmacology , Young AdultABSTRACT
Human keratinocytes are important constituents of the skin immune system. They produce several cytokines, chemokines as well as some complement proteins. As regards soluble complement proteins, so far keratinocytes have been shown to synthesize only C3, factor B, factor H and factor I. Synthesis and regulation of synthesis of other complement proteins has not yet been studied. Here we studied the synthesis of terminal complement components, C5-C9 by human keratinocytes. We also studied the regulation of terminal complement synthesis in keratinocytes by several cytokines, namely, IL-1alpha, IL-2, IL-6, TGF-beta1, TNF-alpha, and IFN-gamma. Human keratinocytes constitutively expressed C5, C7, C8gamma and C9 mRNA but not C6, C8alpha and C8beta mRNA. They released C7 and C9, but not C5, C6 and C8. None of the cytokines tested had any influence on the synthesis of terminal components except TNF-alpha, which strongly upregulated C9 production. In conclusion, we demonstrate that keratinocytes are capable of synthesizing some of the terminal complement components and that the synthesis of C9 is regulated by TNF-alpha.
Subject(s)
Complement System Proteins/metabolism , Cytokines/metabolism , Keratinocytes/immunology , Blotting, Western , Complement System Proteins/analysis , Complement System Proteins/genetics , Humans , RNA, Messenger/analysis , RNA, Messenger/metabolism , Transcription, GeneticABSTRACT
Drug hypersensitivity results from interactions between a pharmacologic agent and the human immune system. However, some reactions involve additional, poorly-understood, non-immunological mechanisms. The clinical picture is usually very similar to that of real allergic reactions and the therapeutic possibilities are also the same. The clinical symptoms (aspecific symptoms, special diseases, fixed drug eruption, and drug-induced internal symptoms), and the therapeutic and diagnostic possibilities are reported.
Subject(s)
Drug Hypersensitivity , Drug Eruptions/diagnosis , Drug Eruptions/physiopathology , Drug Eruptions/therapy , Drug Hypersensitivity/diagnosis , Drug Hypersensitivity/physiopathology , Drug Hypersensitivity/therapy , HumansABSTRACT
Neuropeptides released from the cutaneous sensory nerve endings have neurotransmitter and immunoregulatory roles; they exert mitogenic actions and can influence the functions of different cell types in the skin. The aims of this study were a systematic investigation of the effects of the neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and galanin (GAL) on the inflammatory cytokine production (IL-1alpha, IL-8 and TNF-alpha) of the keratinocytes, and a study of their role in the production and secretion of nerve growth factor (NGF) and its precursor molecule (proNGF). Cultures of normal human keratinocytes were treated with 10(-8)M SP, CGRP, VIP or GAL for 30 min. After different time intervals, cells were harvested for total RNA isolation; in addition, cell lysates and supernatants were collected. The effects of the neuropeptides on the mRNA expressions of the different cytokines and NGF were investigated by Q-RT-PCR and the protein levels were studied by means of ELISA assays and Western blotting. Each of the four neuropeptides induced increases in the expressions of IL-1alpha, IL-8 and TNF-alpha mRNA. Increases appeared in the amount of the IL-1alpha protein in the supernatants of neuropeptide-treated cells, and the IL-8 secretion was mildly elevated, while secretion of TNF-alpha remained undetectable. The four neuropeptides increased the NGF mRNA expression to different extents. In the cell lysates of the keratinocytes, only proNGF could be detected, its concentration in the neuropeptide-treated cells being approximately twice that in the time-matched controls. Both control cultures and neuropeptide-treated cultures were found to secrete proNGF and mature NGF, but neuropeptide-treated cell cultures produced markedly higher (3-7-fold) amounts of NGF-like immunoreactive materials. The results demonstrated that neuropeptides released from cutaneous nerves after an injurious stimulus are able to induce an upregulation of IL-1alpha and IL-8 production; they are additionally able to influence the expressions of proNGF/NGF and their secretion from the keratinocytes. These findings may contribute toward an understanding of the neural influence on skin health and disease.
Subject(s)
Calcitonin Gene-Related Peptide/metabolism , Cytokines/metabolism , Galanin/metabolism , Keratinocytes/metabolism , Nerve Growth Factor/metabolism , Substance P/metabolism , Vasoactive Intestinal Peptide/metabolism , Cells, Cultured , Cytokines/genetics , Female , Humans , Inflammation/metabolism , Keratinocytes/cytology , Protein Precursors/metabolism , RNA, Messenger/metabolismABSTRACT
Galanin (GAL) is a biologically active neuropeptide that is widely distributed in the nervous system. GAL exerts diverse action via the GAL receptors (GALR1, GALR2, and GALR3), which belong in the superfamily of G-protein-coupled transmembrane receptors. In human skin, GAL-like immunoreactivity has been reported in free nerve endings and fibers of the dermis. The extraneuronal expression of GAL has also been demonstrated. Although the GALRs are essential for biological functions, the expressions of different GALR subtypes in cultured human keratinocytes have not yet been investigated. The aim of our study was to investigate the mRNA and protein expressions of the different GALRs in the HaCaT immortalized keratinocyte cell line and in cultured human keratinocytes. When reverse transcription (RT)-polymerase chain reaction (PCR) was used with different GALR-specific primers, only GALR2 mRNA was identified in cultured HaCaT cells and keratinocytes. Sequencing of the PCR products proved the presence of GALR2 mRNA in the keratinocytes. The presence of GALR2 protein was next investigated, using a polyclonal antibody against human GALR2. Both the HaCaT cells and the cultured keratinocytes displayed specific immunohistochemical staining, with higher intensity on the surface of the keratinocytes. Immunohistochemical investigations of normal human skin specimens revealed that GALR2 was expressed with high intensity in the basal layer of the epidermis and also around the hair follicles in the dermis. GAL treatment of the keratinocytes resulted in an increase in cytosolic Ca2+ concentration, suggesting that GALR2 is a functional receptor. Further studies are necessary to clarify the biological effects of GAL in the skin.
Subject(s)
Gene Expression/physiology , Keratinocytes/metabolism , Receptors, Galanin/metabolism , Skin/cytology , Adult , Blotting, Western/methods , Calcium/metabolism , Cells, Cultured , Female , Humans , Immunohistochemistry/methods , In Situ Hybridization/methods , RNA, Messenger/metabolism , Receptors, Galanin/classification , Receptors, Galanin/genetics , Reverse Transcriptase Polymerase Chain Reaction/methodsABSTRACT
Bullous pemphigoid (BP) is characterized immunologically by tissue-bound and circulating autoantibodies targeting the hemidesmosomal proteins BP230 and BP180. Recent evidence suggests a pathophysiological role for autoantibodies against alpha6 integrin in the subepidermal blister formation of oral pemphigoid. The objective of our study was to investigate the presence of anti-alpha6 integrin antibodies in patients with classical BP. The autoantibody profiles of 30 patients with BP, 10 patients with pemphigus vulgaris, and 20 healthy persons were identified. With the use of PeptideStructure and PlotStructure software, four different antigenic epitopes for alpha6 integrin were predicted, and their fusion recombinant constructs were prepared in an E. coli expression system. Sera were tested for alpha6 integrin autoantibodies by an ELISA technique. Altogether, 52% of the patients with BP displayed circulating antibodies against at least one recombinant protein. Our findings provide the first evidence for the presence of anti-alpha6 integrin antibodies in patients with classical BP.
Subject(s)
Autoantibodies/blood , Integrin alpha6/immunology , Pemphigoid, Bullous/immunology , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle AgedSubject(s)
Lymphedema/therapy , Nail Diseases/therapy , Physical Therapy Modalities , Humans , Lymphedema/diagnosis , Male , Middle Aged , Nail Diseases/diagnosis , SyndromeABSTRACT
Bullous pemphigoid (BP) is an IgG-mediated autoimmune blistering disease that targets the hemidesmosomal proteins BP230 and BP180. To investigate the pathogenic role of anti-BP230 antibodies, rabbit polyclonal antibodies were generated against an antigenic sequence of the human BP230 antigen (BPAG 1, 2479-2499), which shows 67% homology in the human and the mouse BP230. Purified IgG from the rabbit anti-serum was transferred subcutaneously into the dorsal skin of neonatal isogeneic CBA/Ca (CBA) mice in a dose of 5 mg (n=7) or 1.2 mg IgG/50 microl (n=16). After 24 h, 1 of the mice injected with 5 mg IgG exhibited blisters, but the dorsal skin of all 7 of them was erythematous, and gentle friction produced a fine persistent wrinkling of the epidermis in 4 mice. The mice injected with 1.2 mg IgG developed less severe symptoms. Immunohistological examinations revealed linear rabbit IgG and mouse C3 depositions along the basement membrane of the perilesional skin and subepidermal blister formation. An intradermal inflammatory reaction (granulocyte infiltration) was also detected. None of these symptoms was seen in mice injected with IgG from a control rabbit anti-serum. These findings demonstrate that antibodies against BP230 can elicit the clinical and immunopathological features of BP in neonatal mice, suggesting that anti-BP230 antibodies may possibly play a pathogenic role in this disease.
Subject(s)
Carrier Proteins/immunology , Cytoskeletal Proteins/immunology , Epitopes/immunology , Nerve Tissue Proteins/immunology , Pemphigoid, Bullous/immunology , Amino Acid Sequence , Animals , Animals, Newborn , Carrier Proteins/chemistry , Carrier Proteins/genetics , Carrier Proteins/metabolism , Cytoskeletal Proteins/chemistry , Cytoskeletal Proteins/genetics , Cytoskeletal Proteins/metabolism , Disease Models, Animal , Dystonin , Humans , Immune Sera/immunology , Immunization, Passive , Immunoglobulin G/administration & dosage , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunohistochemistry , Mice , Molecular Sequence Data , Nerve Tissue Proteins/chemistry , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Pemphigoid, Bullous/pathology , Rabbits , Sequence AlignmentABSTRACT
The authors present a 51-year-old patient with clinical signs of acrodermatitis continua suppurativa of the toes. Since histological findings failed to unambiguously support the diagnosis of acrodermatitis continua suppurativa, immunohistology was performed. The results showed intercellular epidermal fluorescence. The subsequent clinical picture (vegetating formation), the repeated histological examination (suprabasal cleft and eosinophilia), as well as the data of immunohistological findings supported the diagnosis of pemphigus vegetans Hallopeau. The patient was treated successfully with a combination of cyclosporine-A and low-dose steroid therapy. The case is of special interest, because there is only a single publication about phalangeal and nail involvement in Hallopeau's type pemphigus vegetans in the dermatological literature according to our knowledge.
Subject(s)
Acrodermatitis/pathology , Pemphigus/diagnosis , Female , Humans , Middle Aged , Nail Diseases/pathology , Pemphigus/pathology , SuppurationABSTRACT
The authors followed the frequency of fragrance contact sensitization in Hungary in a multicentre study in the years 1998 and 1999. A total of 3,604 patients were tested with fragrance mix (FM), and positive reactions were observed in 294 (8.2%). In 160 FM hypersensitive patients, the study was continued with patch testing of the mix constituents (cinnamic alcohol, cinnamic aldehyde, eugenol, amyl cinnamic aldehyde, hydroxycitronellal, geraniol, isoeugenol, oak moss absolute). Of the patients tested, 70.6% produced positive reactions to the constituents. FM contact sensitization was mainly observed in female patients (74.4%). The incidence of contact urticaria in FM hypersensitive patients was 6.1%. Simultaneous patch test trials of other environmental contact allergens, in both early and late evaluations, mainly confirmed hypersensitivity reactions to balsams. Female dominance of hypersensitivity reactions observed during testing the individual components of the mix was striking (82.4%). In positive skin reactions, cinnamic alcohol, isoeugenol and oak moss provoked skin symptoms most frequently. We also tested the 104 patients who produced negative reactions to FM with the constituent individual allergens, with 11.9% positive incidence. The clinical symptoms of the patients were above all manifest in the form of contact eczema, located on the hands, face, eyelids and axillae. With this study, the authors, members of the Hungarian Contact Dermatitis Research Group, call attention to one of the most frequent allergens in the environment.