Taina Hasan

Photosensitivity in lupus erythematosus, UV photoprovocation results compared with history of photosensitivity and clinical findings

Photosensitivity, one of the presenting symptoms in lupus erythematosus (LE), is still poorly defined and varying prevalence figures have been reported. The possibility of a coexisting photodermatosis, especially polymorphous light eruption (PLE), has often not been taken into account. We report the results of ultraviolet A (UVA) and B (UVB) photoprovocation tests in 67 clinically photosensitive patients who had confirmed discoid LE (DLE), systemic LE (SLE) or subacute cutaneous LE (SCLE). The results are compared with a detailed history of photosensitivity and with clinical and serological findings. A pathological photoprovocation reaction, graded as weak, moderate or strong, was induced with either UVA or UVB in 69% of patients with LE, in 100% of those with SCLE, in 70% of those with SLE and in 64% of those with DLE, but in none of 14 controls. Only 16% of the pathological reactions were strong and long‐lasting, resembling LE lesions, while 48% were moderate or weak and transient, clinically like PLE. Fifty‐three per cent of the provocation reactions which were biopsied showed a PLE‐like histology or a non‐specific inflammatory reaction, and most of them were clinically moderate or weak reactions of short duration. In the remaining, mostly clinically strong or long‐lasting reactions, the histology was consistent with LE. A history of sunlight sensitivity did not predict a pathological photoprovocation result but a positive association between the presence of SSA/Ro or SSB/La antibodies and a pathological photoprovocation reaction was found. We have shown that PLE coexists with LE and that both PLE‐ and LE‐like lesions can be induced with UV radiation in LE patients.

Occurrence of polymorphous light eruption in lupus erythematosus.

Photosensitivity is a well–known manifestation of lupus erythematosus (LE). Since there are no strict criteria for photosensitivity, varying prevalence figures have been reported. Also, distinction from polymorphous light eruption (PLE) can be difficult. The purpose of this study was to characterize photosensitivity in more detail and to determine the occurrence of PLE in a series of well–documented LE patients. A questionnaire was answered by 337 LE patients seen at dermatology departments in Finland and Sweden, and 63 of the patients were invited for interview. According to the questionnaire. LE lesions were made worse by sunlight in 242 (72%) patients. Symptoms consistent with PLE were reported by 165 (49%) patients. Detailed personal interviews supported the results from the questionnaire, and revealed that PLE had started 2–45 years before the onset of LE in 23 of 37 patients with both diagnoses, and more than 7 years before in 18 of 37 (49%). PLE proved to be common in patients with both systemic and cutaneous LE. The two conditions may often coexist and, in about half of the cases, PLE preceded LE. These two diseases may share pathogenic factors, PLE might predispose to LE in a subgroup of PLE patients.

Evidence for Genetic Association and Interaction Between the TYK2 and IRF5 Genes in Systemic Lupus Erythematosus

Objective. Several candidate genes have been implicated in susceptibility for systemic lupus erythematosus (SLE), a complex autoimmune disease. The proposed genes include members of the type I interferon (IFN) pathway and genes involved in immunological defense functions. Our aim was to systematically replicate 6 such genes, TYK2, IRF5, CTLA4, PDCD1, FCGR2A, and NOD2. Methods. Single-nucleotide polymorphisms in TYK2, IRF5, CTLA4, PDCD1, FCGR2A, and NOD2 were genotyped in 277 SLE patients and 356 healthy controls from Finland, giving a power of 42%–70% for different genes at published allele frequencies. Results. Significant association was seen for rs2304256 (p = 0.0001) and rs12720270 (p = 0.0031) in TYK2 and rs10954213 (p = 0.0043) in IRF5 in our samples, but not for the other genes. We found evidence for genetic interaction (p = 0.014) between rs2304256 in TYK2 and rs10954213 in IRF5, both members of the type I IFN pathway, strengthening the role of the type I IFN pathway in the pathogenesis of SLE. Conclusion. The IFN pathway genes IRF5 and TYK2 may act epistatically in increasing risk for SLE, but our lack of replication does not exclude effects of the other genes studied.

Patch test reactions to cosmetic allergens in 1995–1997 and 2000–2002 in Finland – a multicentre study

Contact sensitivity to cosmetics is common, but the sensitizing chemicals vary between countries and study periods. The present survey aimed at revealing the recent trends in patch test sensitivity with cosmetic chemicals in Finland. We report a retrospective multicentre survey of patch test reactions focusing on cosmetic‐related substances and comparing the test results in 1995–97 with those in 2000–02. The most striking increases in the frequency of the patch test sensitivity were found with balsam of Peru and propolis from 4.0% to 6.2% (P < 0.001) and from 0.5% to 1.4% (P < 0.001), respectively, whereas the most prominent decreases were found with methylchloro/methylisothiazolinone and chlorhexidine diglugonate from 2.4% to 1.3% (P < 0.001) and from 1.2% to 0.5% (P < 0.001), respectively. The level of patch test sensitivity to methyldibromo glutaronitrile increased, although not significantly, from 1.0% to 1.5%. An increasing tendency was also found with hair dye chemicals 4‐aminophenol and toluene‐2,5‐diamine or toluene‐2,5‐diamine sulfate from 1.3% to 3.8% and from 1.4% to 5.2%, respectively, while such a tendency was not found among permanent wave chemicals. The sensitivity level of fragrance mix remained the same (6% − 7%). We conclude that surveys revealing the state of sensitivity to cosmetic chemicals should be performed periodically in different countries.

Contact sensitization to methylisothiazolinone in Finland--a multicentre study.

Background. Antimicrobials constitute the second most common cause of contact allergy to cosmetics. Methylisothiazolinone (MI), previously always used together with methylchloroisothiazolinone (MCI), has recently been approved in the EU for use on its own in cosmetics and also various industrial products. MCI has been classified as an extreme–strong and MI as a strong–moderate sensitizer.

Tyrosine kinase 2 and interferon regulatory factor 5 polymorphisms are associated with discoid and subacute cutaneous lupus erythematosus

Please cite this paper as: Tyrosine kinase 2 and interferon regulatory factor 5 polymorphisms are associated with discoid and subacute cutaneous lupus erythematosus. Experimental Dermatology 2010; 19: 123–131.

Allergy to systemic and intralesional corticosteroids

In this study, allergic reactions to systemic or intralesional corticosteroids were characterized, and skin tests utilized in the diagnosis of corticosteroid allergy. Five patients who had developed a rash when treated with systemic or intralesional hydrocortisone, methylprednisolone, prednisolone or betamethasone, were challenged with oral or intra‐articular corticosteroid preparations, and skin tested. Upon provocation the patients reacted with diffuse erythema principally on the trunk or on the face. The erythema appeared within a period ranging from a few hours to 24 h and faded in 1–3 days. On patch testing, one patient reacted to prednisolone and methylprednisolone, which induced a positive response upon provocation, and two patients were positive to Pivalone®. Patients who were sensitive to hydrocortisone or methylprednisolone, as judged by anamnestic data and provocations, reacted to these corticosteroids in the intradermal tests. Allergy to betamethasone could not be verified by intradermal or patch tests. A combination of intradermal and patch tests is recommended when allergy to systemic or intralesional corticosteroids is suspected. If these skin tests remain negative, provocation is the method of choice.

Replication of GWAS-identified systemic lupus erythematosus susceptibility genes affirms B-cell receptor pathway signalling and strengthens the role of IRF5 in disease susceptibility in a Northern European population

OBJECTIVE A large number of genes, including several not previously implicated in SLE susceptibility, have recently been identified or confirmed by genome-wide association studies (GWAS). In this study, we sought to replicate some of these results in Finnish SLE patients (n = 275) and control individuals (n = 356). METHODS We genotyped 32 single nucleotide polymorphisms (SNPs) in 12 of the best-supported GWAS-identified SLE genes and loci. We further investigated gene-gene interactions between the loci included in the study. RESULTS The strongest evidence of association was found at the IRF5-TNPO3 locus, with the most significant P-value being 2.0 × 10(-7) and an odds ratio of 1.95 (95% CI 1.51, 2.50). Association between SLE and TNFAIP3, FAM167A-BLK, BANK1 and KIAA1542 was also confirmed, although at a lower significance level and contribution to individual risk. No significant association was found with 1q25.1, PXK, ATG5, ICA1, XKR6, LYN and SCUBE1. Furthermore, no significant gene-gene interactions were detected. CONCLUSION Replication of previous GWAS findings across diverse populations is of importance to validate these associations and to get a better understanding of potential genetic heterogeneity between populations in SLE susceptibility. Our results attest the importance of B-cell receptor pathway and IFN signalling in SLE pathogenesis.

Polymorphisms of the ITGAM Gene Confer Higher Risk of Discoid Cutaneous than of Systemic Lupus Erythematosus

Background Lupus erythematosus (LE) is a heterogeneous disease ranging from mainly skin-restricted manifestations (discoid LE [DLE] and subacute cutaneous LE) to a progressive multisystem disease (systemic LE [SLE]). Genetic association studies have recently identified several strong susceptibility genes for SLE, including integrin alpha M (ITGAM), also known as CD11b, whereas the genetic background of DLE is less clear. Principal Findings To specifically investigate whether ITGAM is a susceptibility gene not only for SLE, but also for cutaneous DLE, we genotyped 177 patients with DLE, 85 patients with sporadic SLE, 190 index cases from SLE families and 395 population control individuals from Finland for nine genetic markers at the ITGAM locus. SLE patients were further subdivided by the presence or absence of discoid rash and renal involvement. In addition, 235 Finnish and Swedish patients positive for Ro/SSA-autoantibodies were included in a subphenotype analysis. Analysis of the ITGAM coding variant rs1143679 showed highly significant association to DLE in patients without signs of systemic disease (P-value  = 4.73×10−11, OR  = 3.20, 95% CI  = 2.23–4.57). Significant association was also detected to SLE patients (P-value  = 8.29×10−6, OR  = 2.14, 95% CI  = 1.52–3.00), and even stronger association was found when stratifying SLE patients by presence of discoid rash (P-value  = 3.59×10−8, OR  = 3.76, 95% CI  = 2.29–6.18). Significance We propose ITGAM as a novel susceptibility gene for cutaneous DLE. The risk effect is independent of systemic involvement and has an even stronger genetic influence on the risk of DLE than of SLE.

An epidemic of contact allergy to methylisothiazolinone in Finland

Kaija Lammintausta1, Kristiina Aalto-Korte2, Leena Ackerman3, Kristiina Alanko3, Päivikki Berry4, Taina Hasan5, Renata Kaminska6, Laura Korhonen5, Arja Laukkanen7, Jussi Liippo1, Maria Pesonen2, Tapio Rantanen8, Riita Riekki9 and Katri Suuronen2 1Department of Dermatology, Turku University Hospital, 20521 Turku, Finland, 2Department of Dermatology, Finnish Institute of Occupational Health, Control of Hypersensitivity Diseases, 00250 Helsinki, Finland, 3Department of Dermatology, Skin and Allergy Hospital, 00290 Helsinki University Central Hospital, Helsinki, Finland, 4Department of Dermatology, Allergy Centre, North Carelia Central Hospital, 80210, Joensuu, Finland, 5Department of Dermatology, Tampere University Hospital, 33521 Tampere, Finland, 6Department of Dermatology, Central Hospital of Keski-Pohjanmaa, 67200 Kokkola, UK, 7Department of Dermatology, Kuopio Unievrsity Hospital, 70211 Kuopio, Finland, 8Department of Dermatology, Central Hospital, Päijät-Häme Social and Health Care Group, 15850 Lahti, Finland, and 9Department of Dermatology, Oulu University Hospital, 90029 Helsinki, Finland