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PubMed1997

Herpetiform pemphigus showing reactivity with pemphigus vulgaris antigen (desmoglein 3)

We report a patient with herpetiform pemphigus (HP) who showed reactivity only with pemphigus vulgaris (PV) antigen but not with pemphigus foliaceus (PF) antigen. Direct and indirect immunofluorescence revealed keratinocyte cell surface staining in the lower layers of the epidermis, where desmoglein 3 (Dsg3) is expressed. Immunoblot analysis, using ethylenediamine tetra-acetic acid-separated human epidermal extracts, revealed that the patient's serum recognized only a 130-kDa polypeptide which co-migrated with Dsg3. By antigen-specific immunoadsorption studies, using desmoglein 1 (Dsg1) and Dsg3 recombinant protein produced by baculovirus expression system, immunoreactivity of the patient's serum was completely adsorbed by Dsg3 alone, but not by Dsg1. These results indicate that this HP patient produced only anti-Dsg3 autoantibodies and no other autoantibodies against components of the keratinocyte cell surface. HP could be a variant of PV, in addition to PF, with unique clinical and histological features.

Autoantigens↗
PubMed1991

HLA class II antigens are associated with Japanese pemphigus patients.

We investigated the HLA class II antigens in 30 Japanese cases of pemphigus, 17 cases of pemphigus vulgaris (PV) and 13 cases of pemphigus foliaceus (PF), by both serologic and restriction fragment length polymorphism (RFLP) analyses. We detected two major haplotypes susceptible to PV, i.e., DRw12-DQw7 and DRw6-DQw5. In contrast, DR2 was absent in PV. RFLP analyses showed that DRw6 PV patients had a disease-associated restriction fragment representing DQw5, the same association as that found in DRw6 Jewish PV patients. However, DRw12 Japanese PV patients had DQw7, whereas DR4 Jewish PV patients had DQw8. On the other hand, all 13 PF patients were serologically typed for DQw1, which could not be further subdivided into DQw5 by RFLP analyses. These results suggest that Japanese and Jewish PV patients may be immunogenetically closely related to each other, but Japanese PV patients appear to be immunogenetically different from Japanese PF patients.

Autoantibodies↗
PubMedDate not supplied

[Anatomopathology and direct and indirect immunofluorescence of lesions of endemic pemphigus foliaceous resistant to corticoid therapy].

A group of 16 patients with endemic pemphigus foliaceus under corticotherapy and still showing erythematous, papulous, verrucous, in general hyperpigmented lesions, which were characterized as cortico therapy resistant lesions, were studied. Such study was made through anatomopathology and direct immunofluorescence (DIF). Anatomopathologically, such lesions showed tendencies to epithelial hyperplasia and cleavage in variable levels at the epidermis what differs from the early lesions of EPF and coincides with the chronic injuries of the EPF of the pre-corticoid era. The DIF of the injured skin was positive for IgG in 93.75% of cases, as it happens in the early stages of EPF, being negative in a simple case in which there was not cleavage. In addition, in eight of those patients, the DIF of the healthy skin and the indirect immunofluorescence (IIF) were studied. The DIF was positive in three of these cases and in all eight the IIF was negative.

Adolescent↗
PubMed2004

Elevated expression of CD23 on peripheral blood B lymphocytes from patients with bullous pemphigoid: correlation with increased serum IgE.

BACKGROUND: Increased serum IgE levels are occasionally found in patients with severe bullous pemphigoid (BP). CD23, a low affinity Fc receptor for IgE, is mainly expressed on mature B lymphocytes. Studies have suggested that serum levels of soluble CD23 (sCD23) correlate with serum IgE levels and disease severity in BP. OBJECTIVE: The purpose of our study is to examine whether the expression of CD23 is elevated in BP and whether this expression correlates with serum IgE levels and disease severity. METHODS: We measured CD23 expression on B cells from patients with active BP, pemphigus vulgaris, pemphigus foliaceus, and atopic dermatitis (AD), as well as healthy control subjects, using a flow cytometer. Serum levels of IgE and sCD23 were also measured. RESULTS: The expression of CD23 was significantly higher in BP patients compared with healthy control subjects (P < 0.05), whereas the levels were normal in the other bullous diseases. CD23 expression tended to be higher in severe BP compared with moderate BP, and the levels in severe BP were comparable to the levels in AD. Furthermore, CD23 expression correlated positively with serum IgE levels (P < 0.002), and the IgE levels were significantly higher in severe BP than in moderate BP (P < 0.01 ). CD23 expression in BP did not correlate with sCD23 levels. CONCLUSIONS: These results suggest that the up-regulated surface CD23 on B cells may be involved in IgE synthesis and inflammatory events in BP.

Adult↗
PubMed1996

Profile of alopecia areata in Northern India.

BACKGROUND: Epidemiologic studies of alopecia areata (AA) are available from USA, Japan and European countries, but there is a paucity of literature on AA from Asian countries, especially from the Indian subcontinent. METHODS: In a prospective, hospital-based study lasting for a decade (1983-1992), the epidemiology of AA was studied, including associated diseases and risk factors for development of severe AA. Simultaneously a similar study was carried out in age- and sex-matched controls. RESULTS: Eight hundred and eight patients (532 men, 276 women) and 572 age- and sex-matched controls (370 men, 202 women) were studied. The incidence of AA was 0.7% of new dermatology outpatients. The majority of patients (712, 88%) were below 40 years of age, including 196 children < 16 years of age (24%). Almost half (46%) of the women patients had onset of AA in childhood, compared to only 19% in men (P < 0.001). Alopecia was total, universal, or extensive in 154 patients (19%). An onset in the first two decades was more often associated with severe alopecia (P < 0.001), especially in men (P < 0.01). Alopecia areata was recorded in family members of 70 patients (9%), being more frequent in the severe forms of AA (16%). Evidence of atopy was recorded in a total of 146 instances (18%). The frequency of atopy was the same in circumscribed alopecia (18.1%) and severe alopecia (18.2%). Nail changes were found in 162 patients (20%) and were more frequent in 76 (47%) with the severe form of AA (P < 0.001). On 39 occasions (5%), autoimmune-related diseases were detected: vitiligo in 15 (1.8%), thyroid disorders in 8 (1%), lichen planus in 6 (0.7%), collagen vascular diseases in 5 (0.6%), diabetes mellitus in 4 patients (0.4%), and pemphigus foliaceus in 1 (0.1%) patient. Patients with family members having vitiligo (recorded in 5.9% of patients), were more frequently affected with severe alopecia (P < 0.001). CONCLUSIONS: Alopecia areata in North Indians showed a preponderance in men (M:F = 2:1) and the majority of persons with disease (88%) were below 40 years of age. Onset in childhood was more frequent in girls or women, but the incidence of severe alopecia was higher in boys or men with onset at an earlier age. Diseases associated with autoimmunity were seen in only 5% of patients. Atopy was found to be associated in 18% of patients, but its reported association with younger age of onset and severe alopecia was not confirmed. Presence of vitiligo in family members and onset before 20 years of age, especially in boys or men, were found to be risk factors for severe alopecia.

Adolescent↗
PubMed1993

[Dexamethasone-cyclophosphamide pulse therapy in bullous autoimmune dermatoses].

The problem in the treatment of bullous autoimmune dermatoses with long-term corticosteroids is that the high doses cause side-effects. An alternative form of therapy with high-dose dexamethasone-cyclophosphamide pulses was used to treat 20 patients between 33 and 86 years: 7 patients had bullous pemphigoid, 6 pemphigus vulgaris, 5 pemphigus foliaceus, and 2 cicatricial pemphigoid. On each of days 1-3 100 mg dexamethasone was administered i.v. and on day 1, 500 mg cyclophosphamide i.v. In the therapy interval between the pulses 50 mg cyclophosphamide per day. Initially the pulses were repeated every 2 weeks and later at 10-week intervals. After 6 months of this regimen 13 patients were symptom-free, 4 had improved, and 3 showed no change. The efficacy of treatment was equal in newly diagnosed and previously treated cases. (Side-effects were leucopenia (n = 3), myalgia and arthralgia (n = 2), taste disturbance (n = 2), diffuse hair loss (n = 2), thrombophlebitis (n = 1), herpes zoster (n = 1) and a delayed-type hypersensitivity reaction to mesna. Owing to the rather short follow-up, no conclusions on long-term side-effects of this therapy are possible. However, dexamethasone-cyclophosphamide pulse therapy appears so far to be a good alternative to the standard continuous corticosteroid treatment.

Adult↗
PubMed2000

A study of desmoglein 1 autoantibodies in pemphigus vulgaris: racial differences in frequency and the association with a more severe phenotype.

BACKGROUND: Pemphigus vulgaris (PV) is characterized by pathogenic autoantibodies to desmoglein (Dsg) 3, but additional antibodies to Dsg1, the pemphigus foliaceus antigen, are detectable in some cases. OBJECTIVES: To investigate the clinical significance of the presence of both Dsg 1 and 3 antibodies. METHODS: In 79 subjects with PV, enzyme-linked immunosorbent assays were used to detect IgG autoantibodies reactive with the ectodomain of Dsg1 and Dsg3. RESULTS: There was a clear association between the clinical phenotype and the Dsg antibody profile. All subjects had Dsg3 autoantibodies and 61% had coexisting Dsg1 antibodies (Dsg3+/Dsg1+). PV limited entirely to the mucosal surfaces was seen only in Dsg3+/Dsg1- patients, while additional Dsg1 antibodies (Dsg3+/Dsg1+) predicted cutaneous in addition to mucosal involvement. Although minor cutaneous involvement was observed in most Dsg3+/Dsg1- patients, severe cutaneous involvement was seen only in Dsg3+/Dsg1+ patients. Dsg1 antibodies were detectable early in the course of disease and their appearance did not relate to the use of systemic therapy. The proportion of Dsg1+ patients was higher in those of Indian origin compared with white northern Europeans (P < 0.05). CONCLUSIONS: These data suggest that the presence of Dsg1 antibodies is predictive of a potentially more severe disease and that genetic factors may determine the Dsg antibody profile.

Autoantibodies↗
PubMedDate not supplied

Study of upper gastrointestinal tract involvement in pemphigus by esophago-gastro-duodenoscopy.

INTRODUCTION: Involvement of upper gastrointestinal tract in pemphigus vulgaris is not uncommon. AIM: To study the involvement of upper gastrointestinal tract (UGIT) with the help of esophago-gastro-duodenoscopy (EGD) in patients of vesiculobullous dermatoses with emphasis on pemphigus vulgaris. METHODS: Forty-two patients (M-22, F-20) with vesiculobullous dermatoses, diagnosed on the basis of clinical features and skin histopathology as pemphigus vulgaris (PV)-40 patients and pemphigus foliaceus (PF)-2 patients were included in the study. The EGD was performed and mucosa of the esophagus, stomach and first part of the duodenum were examined. Mucosal biopsies were taken from the lower esophagus in 26 patients of PV and studied after H and E staining. RESULTS: On EGD, esophageal involvement was seen in 67% patients of PV (27/40). Of these, Grade I esophagitis was observed in seven, Grade II in 11, Grade III in four and Grade IV involvement was seen in five patients of PV. Three PV patients had associated esophageal candidiasis. Involvement of esophageal mucosa was also observed in one out of two patients of PF. Gastric mucosa was involved in 52% and duodenal mucosa in 20% of PV patients. Acantholysis was observed in seven out of 26 (27%) esophageal biopsies of PV patients. Two patients of PV vomited a tube-like structure, indicative of 'esophagitis dissecans superficialis'. The involvement of the gastric mucosa in patients with history of oral corticosteroid intake (60%) was compared to the group without history of oral corticosteroids (30%). CONCLUSION: Among PV patients under study, significant involvement of oral (87%), esophageal (67%), gastric (52%) and duodenal mucosa (20%) was observed.

Adolescent↗
PubMed2002

Diagnostic features of pemphigus vulgaris in patients with bullous pemphigoid. Molecular analysis of autoantibody profile.

BACKGROUND: The simultaneous presence of features of pemphigus vulgaris (PV) in patients with bullous pemphigoid (BP) has previously been reported in the literature. OBJECTIVE: The purpose of this retrospective study is to present 13 patients with an initial diagnosis of BP, who subsequently demonstrated coexistent serological features of both BP and PV. METHODS: The following information on each patient was documented, at the time of initial diagnosis: clinical profile on presentation, histology, direct immunofluorescence, indirect immunofluorescence (IIF) using monkey esophagus as substrate, salt-split skin (SSS) and an immunoblot assay. Since all 13 patients failed to respond to conventional systemic therapy, intravenous immunoglobulin (IVIg) was used as an alternative treatment modality. Prior to initiating IVIg therapy, in all 13 patients, serological studies were performed. In addition to IIF using monkey esophagus, an immunoblot assay and SSS, an enzyme-linked immunosorbent assay (ELISA) was performed to detect antibodies to desmogleins. These different assays were done to identify pathological autoantibodies typical of BP and PV. A control group of 25 healthy normal individuals, 37 patients with BP, 17 patients with PV and 12 patients with pemphigus foliaceus were used for comparison of serological studies. RESULTS: At the time of initial presentation, histological and immunopathological studies confirmed the diagnosis of BP in all 13 patients. Prior to the initiation of IVIg therapy, results of IIF using monkey esophagus as substrate demonstrated high levels of anti-intercellular cement substance (anti-ICS) or antikeratinocyte cell surface antibody. Sera of all 13 patients on SSS bound to the epidermal side of the split. In an immunoblot, using bovine gingival lysate as substrate, sera of 6 patients bound to both a 230-kD (BP Ag1) and 180-kD protein (BP Ag2), while 7 sera bound to only a 230-kD protein. All 13 patients had high levels of antibodies to desmoglein 3 on ELISA. In a pilot experiment, the anti-ICS antibody in sera from 6 random patients was found to be predominantly of the IgG4 subclass. Use of IVIg resulted in an effective clinical response and the maintenance of a prolonged clinical remission. CONCLUSION: In patients with BP, who are nonresponsive to conventional therapy, the presence of two autoimmune diseases or a dual diagnosis should be considered.

Aged↗
PubMed2000

Diagnosis of pemphigus by ELISA: a critical evaluation of two ELISAs for the detection of antibodies to the major pemphigus antigens, desmoglein 1 and 3.

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are characterized by autoantibodies to the desmosomal glycoproteins desmoglein 3 (Dsg 3) and Dsg 1 (Dsg 1), respectively. In this study, two enzyme-linked immunosorbent assays (ELISA) which detect IgG autoantibodies to Dsg 1 and Dsg 3 have been evaluated. A total of 317 normal and disease controls, 82 patients with PV and 25 with PF were studied. The Dsg 3 ELISA was positive in all 34 patients with untreated PV and the Dsg 1 ELISA was positive in all 10 with untreated PF. When patients undergoing treatment were included, the sensitivities fell to 95% and 92%, respectively, but still compared favourably to the sensitivity of indirect immunofluorescence which was 79% in PV and 84% in PF. All PF sera were negative in the Dsg 3 ELISA and the specificity of both assays was 98% or greater. Large numbers of samples could be analysed simultaneously over a relatively short time period. The Dsg 1 and Dsg 3 ELISAs also provided objective, quantitative, reproducible data which allowed differentiation of PV from PF and in view of these advantages, they are likely to become a routine technique in diagnostic laboratories.

Adolescent↗
PubMed2005

The interaction of pemphigus autoimmunoglobulins with epidermal cells: activation of the fas apoptotic pathway and the use of caspase activity for pathogenicity tests of pemphigus patients.

Pemphigus is a fatal autoimmune disease in which autoimmunoglobulins PV-IgG (binding to desmoglein 3) and PF-IgG (binding to desmoglein 1) in pemphigus vulgaris and pemphigus foliaceus, respectively, cause intraepidermal blisters, cell-cell separation (acantholysis), and cell death. The mechanism of acantholytic lesion formation has not yet been elucidated. Recently, we have reported that an apoptotic mechanism might be operative in PV-IgG-induced acantholysis: (1) in patients' lesional and some perilesional skin portions, the FasR pathway is activated as its components were enriched; (2) in cultured keratinocytes, PV-IgG upregulates effectors of the FasR pathway (including the mitochondrial loop), as found by immunodetermination (cytochemistry, Western blot of pathway effectors) and determination of caspases 1, 3, and 8 activity/activation; (3) in organ cultures of skin incubated with PV-IgG, activated caspase 8 was found also in perilesional cells and coaggregated with bound PV-IgG; (4) caspase 8 activation in DISCs precedes caspase 3 activation in keratinocytes in cultures upon incubation with PV-IgG. Because caspase activation was shown to accompany lesion formation in cell and organ cultures incubated with PV-IgG, we used caspase activity to monitor the pathogenicity of PV-IgG in relation to PV-IgG binding to epithelia. A rough correlation was found between sera titers, determined by IIF and by immunoblot binding to desmoglein 3, and activation of caspase 3.

Acantholysis↗
PubMed2004

Anti-desmoglein-1 antibodies in onchocerciasis, leishmaniasis and Chagas disease suggest a possible etiological link to Fogo selvagem.

Pemphigus foliaceus (PF) and the endemic form Fogo Selvagem (FS) are mediated by pathogenic antibodies to the EC1-2 domains of desmoglein-1. There is a preclinical phase with antibodies to only EC5. Based on geographic clustering of cases, FS is thought to have an, as yet unidentified, environmental trigger. In this study we have searched for anti-desmoglein-1 antibodies in sera from parasitic (leishmaniasis, Chagas, and onchocerciasis), and infectious diseases (leprosy and South American (SA) blastomycosis), which are prevalent in the same geographic regions of Brazil as FS. A specific and sensitive desmoglein-1 ELISA detected antibodies in 34 of 41 onchocerciasis (83%), 38 of 88 leishmaniasis (43%), 18 of 31 Chagas disease (58%), 7 of 28 SA blastomycosis (25%), and 14 of 83 leprosy sera (17%). These sera recognized epitopes restricted to the EC5 domain. These findings identify several etiological factors for FS. It is hypothesized that a component of insect vector saliva, rather than the parasite itself may trigger an antibody response to EC-5. In persons with the known HLA susceptibility alleles and living in endemic areas, a response to the EC1-2 domains may subsequently develop by epitope spreading with associated clinical signs of FS.

Antigens, Protozoan↗
PubMed2005

Intravenous dexamethasone-cyclophosphamide pulse therapy in comparison with oral methylprednisolone-azathioprine therapy in patients with pemphigus: results of a multicenter prospectively randomized study.

BACKGROUND: Pemphigus is a potentially life-threatening autoimmune blistering skin disease usually treated with high-dose corticosteroids in combination with immunosuppressive drugs. In a multicenter, prospectively randomized study we compared efficacy and side effects of a dexamethasone-cyclophosphamide (D/C) pulse therapy with a methylprednisolone-azathioprine (M/A) therapy in 22 patients with newly diagnosed pemphigus vulgaris and pemphigus foliaceus. PATIENTS AND METHODS: The 11 patients of the M/A group were treated with daily doses of methylprednisolone (initially 2 mg/kg body weight) and azathioprine (2-2,5 mg/kg body weight) which were subsequently tapered. D/C pulse therapy in 11 patients consisted of intravenous administration of 100 mg dexamethasone/d on 3 consecutive days along with cyclophosphamide (500 mg) on day one. Pulses were initially repeated every 2-4 weeks and then at increasing intervals. In between the pulses, oral cyclophosphamide (50 mg) was given daily for 6 months. RESULTS: Within 24 months after treatment initiation, 5/11 patients of the D/C group had a remission (complete remissions after discontinuation of therapy in 3 patients) and 6/11 patients had a progression. In the M/A group, there were remissions in 9/11 patients (complete remissions after discontinuation of therapy in 3 patients) and progression in 1/11 patients. There were more relapses in M/A therapy after remission than in D/C therapy. Side effects were more common in the M/A group. These differences were not significant (p > 0,05). CONCLUSION: Because of the high number of progressions in patients treated with D/C therapy, we can not confirm the encouraging results of earlier reports about pulse D/C therapy. Nevertheless D/C therapy seemed to be better tolerated and, in case of primary efficacy, was associated with fewer recurrences than M/A therapy.

Administration, Oral↗
PubMed2002

Increased incidence of pemphigus vulgaris in southern Europeans living in Germany compared with native Germans.

BACKGROUND: The two major subtypes of pemphigus include: pemphigus vulgaris (PV) and pemphigus foliaceus. Only limited data are available on the epidemiology of these diseases. OBJECTIVE: The aim of the present study was to estimate the gender- and age-specific incidences of PV in two well-defined regions of Germany and to compare the incidences among native Germans with those in citizens from other countries living in Germany. METHODS: We performed a retrospective review of records from all patients that were diagnosed with PV at the Departments of Dermatology in Würzburg and Mannheim between 1989 and 1997. RESULTS: During the observation period, 14 patients were diagnosed with PV coming from an area with 1.46 million residents. With regard to the patients' age, the highest incidence for women was found in the 51-65-year-old-age group with 2.34 [95% confidence interval (CI): 0.36; 7.76] new cases per 1 million inhabitants per year. The highest incidence for men was observed in the over 65-year-old age group with 3.72 (95% CI: 0.95; 9.8) cases/million peryear. In the 51-65-year-old age group,we found a 25-foldhigher incidence of PV in foreigners living in Germany compared with native Germans. The age-adjusted incidence of PV was ninefold higher in foreigners compared with native Germans. Interestingly, all non-German patients came from two southern European countries (Turkey and Italy). CONCLUSIONS: The age-adjusted incidence of PV differs between native Germans and foreigners living in Germany. Further studies are necessary to address the risk factors (genetic and/or environmental) that contribute to this difference.

Aged↗
PubMed2001

Upregulation of P-cadherin expression in the lesional skin of pemphigus, Hailey-Hailey disease and Darier's disease.

BACKGROUND: Autoimmune blistering diseases, pemphigus vulgaris (PV) and pemphigus foliaceus (PF), are known to be caused by binding of autoantibodies to the desmosomal cadherins, desmoglein 3 and desmoglein 1, respectively. Recently, mutations in the genes coding Ca2+ pumps leads to inherited blistering diseases, Hailey-Hailey disease (HHD) and Darier's disease (DD). Cadherins are a family of Ca2+-dependent cell adhesion molecules and P-cadherin is one of the major cadherins expressed in the epidermis. Although detailed mechanisms of acantholysis of these blistering diseases have not been fully clarified, abnormal expression of cadherins caused by altered Ca2+ concentration due to the binding of autoantibodies to cell surface or by mutations in Ca2+ pumps is suggested to be involved in mechanisms of acantholysis of these autoimmune and inherited blistering diseases. The purpose of the present study was to determine whether altered P-cadherin expression is present in these diseases. METHOD: Distribution patterns of P-cadherin in skin specimens from patients with PV (n=2), PF (n=2), HHD (n=4) and DD (n=3), were examined with confocal laser scanning microscopy using two anti-P-cadherin antibodies, 6A9 and NCC-CAD-299. RESULTS: In normal control skin, P-cadherin expression was restricted to the basal layer. In contrast, positive immunostaining of P-cadherin was observed not only in the basal cells, but also in the suprabasal cells in lesional skin of all the acantholytic diseases. CONCLUSIONS: The present results clearly demonstrated that upregulation of P-cadherin expression occurs in the acantholysis in all the four blistering diseases PV, PF, HHD and DD. Upregulation of P-cadherin may be involved in the pathomechanism of both the autoimmune blistering diseases and the inherited blistering diseases.

Acantholysis↗
PubMed1977

Necrolytic migratory erythema. Distinctive dermatosis of the glucagonoma syndrome.

Glucagon-secreting tumors of the pancreatic islets (glucagonomas) produce a distinctive syndrome in which weight loss, diabetes mellitus, anemia,and prominent mucocutaneous findings occur. The cutaneous component-necrolytic migratory erythema--may be polymorphous, but most commonly manifests as erosions and crusts of the groin, perineum, buttocks, distal part of the extremities, and central area of the face. Alternatively, scaly papules and plaques may predominate in these areas. The eruption may resemble such dermatoses as pemphigus foliaceus, acrodermatitis enteropathica, chronic mucocutaneous candidiasis, psoriasis, and severe seborrheic dermatitis. Two patients with chronic, previously undiagnosed dermatoses had necrolytic migratory erythemia, which led to the discovery of glucagonomas present in each. In one patient surgical resection of the tumor resulted in total clearing of the rash within 48 hours. Awareness of this distinctive entity may lead to early diagnosis and, possibly, cure.

Adenoma, Islet Cell↗
PubMed1998

The expression of desmoglein isoforms in cultured human keratinocytes is regulated by calcium, serum, and protein kinase C.

Three desmoglein (Dsg) isoforms are expressed in a differentiation-specific fashion in the epidermis, with Dsg2 being basal, Dsg3 (pemphigus vulgaris antigen) basal and spinous, and Dsg1 (pemphigus foliaceus antigen) predominantly granular. To better understand the mechanism(s) regulating Dsg isoform expression, we examined the expression pattern of Dsg1, Dsg2, and Dsg3 in normal human epidermal keratinocytes (NHEKs), the immortalized, nontumorigenic HaCaT cell line, and several squamous cell carcinoma cell lines (SCC-9, SCC-12F, SCC-13, and SCC-25). In all cells, the accumulation of high Dsg protein levels required calcium and was not observed in low calcium (0.05-0.07 mM) media. NHEKs expressed Dsg1 in all media tested, consistent with their normal differentiation capacity. HaCaT and SCC-25 also expressed Dsg1; however, the presence of serum in the media dramatically decreased Dsg1 protein levels. Serum also inhibited Dsg1 mRNA levels in HaCaT cells. Dsg1 was not detected in extracts from SCC-9, SCC-12F, and SCC-13 under any conditions. Since activation of protein kinase C (PKC) is involved in keratinocyte differentiation, we evaluated the effects of PKC down-regulation on Dsg isoform expression. Long-term treatment with either the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) or bryostatin 1 inhibited levels of Dsg1 and Dsg3, but not Dsg2 in NHEKs and HaCaT cells. Chronic TPA also decreased Dsg1 and Dsg3 mRNA levels in NHEKs, further supporting a role for PKC activation in the expression of the suprabasal Dsg1 and Dsg3. These results identify several regulatory mechanisms by which the differentiation-specific pattern of desmosomal cadherins is established in the epidermis.

Blood↗
PubMedDate not supplied

Allergic skin reactions in the tropics.

Cutaneous allergic reactions are relatively common in tropical countries, with some caused by the tropical environment and others by changes in the traditional living conditions combined with poverty. HIV infection is a major contributory factor. A large number of reactions are eczematous. Atopic dermatitis is on the increase together with contact allergic reactions. Available products are often of inferior quality and contain irritants and allergens that may be forbidden elsewhere in the world. The extensive and uncontrolled use of drugs and indigenous medications together with an increase in HIV prevalence leads to drug eruptions such as the Stevens-Johnson syndrome and toxic epidermal necrolysis. Poverty plays an important role in the prevalence of insect bites and resulting papular urticaria and possibly in acropustulosis infantum. Many unexplained environmentally induced blistering diseases occur, ranging from phytophotodermatitis to fogo selvagem and from pemphigus foliaceus to chronic bullous dermatosis of childhood. This article describes the allergic conditions that occur in the tropics. Special attention is given to those cases of eczema and eruptions that are specific to tropical countries. Available treatments are also discussed.

Blister↗