Consensus statement on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: Localized scleroderma, systemic sclerosis and overlap syndromes.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present consensus provides an update to the 2017 European Dermatology Forum Guidelines, focusing on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, updated strategies for the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 1 of this consensus provides clinicians with an overview of the diagnosis and treatment of localized scleroderma (morphea), and systemic sclerosis including overlap syndromes.

Comorbidities, mortality and survival in patients with pyoderma gangrenosum: a Danish nationwide registry-nested case-control study.

BACKGROUND: Pyoderma gangrenosum (PG) is an ulcerative skin disease associated with comorbidities and increased mortality; however, the literature on this topic is scarce. OBJECTIVES: To investigate the mortality, prevalence and risk of comorbidities in patients with PG. METHODS: This nationwide registry nested case-control study included all inpatients and outpatients diagnosed with PG in tertiary dermatology centres in Denmark between 1 January 1994 and 31 December 2016. Each case was matched on date of birth and sex with 10 unique controls. The Danish National Patient Registry was used to identify all patients and to gather information on comorbidity. Information on age, sex, vital status and emigration was obtained from the Danish Civil Registration System. The outcomes were 19 different comorbidities and all-cause mortality. Prevalence was assessed from odds ratios (ORs) for specific comorbidities at the time of PG diagnosis. The risk of developing specific comorbidities and death was assessed using hazard ratios (HRs) obtained using the Cox proportional-hazards model. RESULTS: A total of 1604 patients with PG were matched with 16 039 controls. Some associations were known, e.g. inflammatory bowel disease [OR 19·15 (15·27-24·02), HR 6·51 (4·24-10·01)], while others have not been described previously, e.g. osteoporosis [OR 1·57 (1·22-2·02), HR 2·59 (2·08-3·22)]. Mortality was significantly increased among patients with PG [HR 2·79 (2·57-3·03)]. CONCLUSIONS: Patients with PG have increased mortality and an increased prevalence and risk of both previously reported and novel comorbidities that may have severe consequences if left undiagnosed. Our findings are mainly related to moderate and severe PG.

Increased frequency of multiple sclerosis among patients with bullous pemphigoid: a population-based cohort study on comorbidities anchored around the diagnosis of bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is a disease of the elderly and may be associated with neurological and cardiovascular diseases and diabetes. Mortality rates strongly exceed those of the background population. OBJECTIVES: To investigate the frequency of comorbidities and their temporal relation to BP. METHODS: A register-based matched-cohort study on all Danish patients with a hospital-based diagnosis of BP (n = 3281). The main outcomes were multiple sclerosis (MS), Parkinson disease (PD), Alzheimer disease (AD), stroke, diabetes types 1 and 2, malignancies, ischaemic heart disease (IHD), hypertension and eventually death. RESULTS: At baseline, patients with BP had increased prevalences of MS [odds ratio (OR) 9·7, 95% confidence interval (CI) 6·0-15·6], PD (OR 4·2, 95% CI 3·1-5·8), AD (OR 2·6, 95% CI 1·8-3·5) and stroke (OR 2·7, 95% CI 2·4-2·9). Furthermore, malignancies, cardiovascular disease and diabetes were over-represented among patients with BP: type 1 diabetes (OR 3·1, 95% CI 2·5-3·8), type 2 diabetes (OR 2·3, 95% CI 2·0-2·6), malignancies (OR 1·3, 95% CI 1·1-1·4), IHD (OR 1·7, 95% CI 1·5-1·9) and hypertension (OR 2·0, 95% CI 1·8-2·2). During follow-up, the risk of MS was significantly higher among patients with BP [hazard ratio (HR) 9·4, 95% CI 4·9-18·0], even if events during the first year after diagnosis of BP were excluded (HR 5·1, 95% CI 2·3-11·3). Patients with BP had an average increased mortality rate of 2·04 (95% CI 1·96-2·13). CONCLUSIONS: We discovered a significantly increased frequency of MS among patients with BP. At the time of diagnosis, patients with BP had an excessive number of comorbidities and an increased mortality rate over the following years.

Cancer incidence among patients with a hospital diagnosis of pruritus: a nationwide Danish cohort study.

BACKGROUND: Pruritus is a frequent complaint in patients with cancer. However, no large study has examined pruritus as a marker of undiagnosed cancer. OBJECTIVES: To examine the association between inpatient, outpatient and emergency hospital diagnoses of pruritus and subsequent cancer diagnoses. METHODS: In this nationwide Danish cohort study, we used medical databases to identify all patients (n = 12,813) with a diagnosis of pruritus during the period 1978-2011 and followed them until a first-time cancer diagnosis, emigration, death or 31 December 2011. We computed standardized incidence ratios (SIRs) for cancer as the observed to expected number of cancers based on national cancer incidence rates. We calculated the 1-year absolute risk of cancer, treating death as a competing risk. RESULTS: The overall SIR of cancer was 1.13 [95% confidence interval (CI) 1.07-1.20]: 1.22 (95% CI 1.13-1.33) among men and 1.05 (95% CI 0.97-1.14) among women. The SIR was 1.20 (95% CI 1.08-1.33) among patients with a previous diagnosis of dermatological disease and 1.10 (95% CI 1.02-1.18) among patients without such a diagnosis. Both haematological and various solid cancers were observed at increased rates. Overall, the highest SIRs were observed during the first 3 months of follow-up, declining rapidly thereafter. The 1-year absolute risk of a cancer diagnosis was 1.63% and 155 patients with pruritus would have needed to be examined to detect one excess cancer. CONCLUSIONS: Pruritus may be a marker of occult cancer. Further studies are needed to assess the prognostic benefit of screening for cancer in patients with pruritus.

Self-reported skin morbidities and health-related quality of life: a population-based nested case-control study.

BACKGROUND: Impaired dermatological health-related quality of life (HRQoL) has been observed in hospital-based studies, but little is known on a population-based level. OBJECTIVE: To investigate self-reported dermatological HRQoL in the general population. METHODS: Hidradenitis suppurativa, psoriasis, pimples, hand rash or atopic eczema were identified using questionnaires in a 15,177 person population sample. A nested case-control study of 180 cases and 259 controls was made using the Dermatology Life Quality Index (DLQI), Skindex-29 and EQ-5D. RESULTS: Cases had higher scores in DLQI and Skindex-29 and a lower score in EQ-5D, suggesting lower HRQoL. Adjusting for age and sex, the differences in Skindex-29 and DLQI were significant (p < 0.001). CONCLUSIONS: Persons with self-reported skin morbidity had lower HRQoL than the general population. The impairment is not as significant as in studies of hospital-based cases, but considering the high prevalence of skin diseases it may still represent a significant burden of disease on society in aggregate.

The impact of comorbidity and stage on prognosis of Danish melanoma patients, 1987-2009: a registry-based cohort study.

BACKGROUND: Comorbid conditions may play an important role in the prognosis of melanoma patients but have received little attention. METHODS: Using data from Danish registries, we identified patients diagnosed with melanoma from 1987 to 2009. We estimated the prevalence of comorbidity and calculated mortality rate ratios and interaction risks between melanoma and comorbidity. For every melanoma patient, 10 individuals were selected for comparison. Individuals in the comparison cohort were matched to their corresponding melanoma patients on age, gender, and exact prevalent comorbidities. RESULTS: We included 23 476 patients, 81% of whom had no comorbidity. Higher prevalence of comorbidity was associated with more advanced cancer stage. The standardised mortality rate increased with increasing level of comorbidity in both cohorts and was consistently higher among melanoma patients. Melanoma and comorbidity interacted to increase the mortality rate. The highest proportional excess was seen in melanoma patients with comorbidity score 3, in whom interaction accounted for 77 deaths per 1000 person-years (40% of the total rate). We stratified by cancer stage and found that the interaction was markedly concentrated in patients with distant metastases. CONCLUSION: Interaction between melanoma and comorbidity was primarily concentrated in patients with distant metastases, which raises the possibility that comorbidity is associated with delay of melanoma diagnosis, advanced cancer stage, and less aggressive melanoma treatment.

Antifibrotic effect after low-dose imatinib mesylate treatment in patients with nephrogenic systemic fibrosis: an open-label non-randomized, uncontrolled clinical trial.

BACKGROUND: Nephrogenic systemic fibrosis is a disease affecting the connective tissue of the skin and internal organs in patients with renal failure. No effective treatments are available. OBJECTIVES: To investigate if the tyrosine kinase inhibitor, imatinib mesylate was effective in patients with moderate to severe nephrogenic systemic fibrosis. METHODS: Among 25 patients with nephrogenic systemic fibrosis evaluated for the study from 1 October 2009 to 1 December 2010, four were included. They were treated with oral imatinib mesylate at a start dose of 400 mg/day. MAIN OUTCOME MEASURE: Reduction of skin fibrosis and increase in joint mobility evaluated by the modified Rodnan skin score and a goniometer. RESULTS: In two patients, the imatinib mesylate dose was reduced to 200 mg/day and in one patient to 100 mg/day. Two patients were treated for 24 weeks, one patient for 16 weeks and one patient for 4 weeks. Three patients experienced tethering of their skin which lessened with reduction in modified Rodnan skin score from 24 to 20, 24 to 17 and 21 to 14 but with very limited changes in joint mobility. The fourth patient discontinued the treatment due to a complicating infection. CONCLUSION: Imatinib mesylate may be an effective drug in the treatment of skin fibrosis in moderate to severe NSF cases, even at reduced doses. We found a positive clinical effect on the skin, but no convincing improvement of the joint mobility. Only few patients could be recruited limiting the interpretation and conclusions of the results.

Nephrogenic systemic fibrosis is found only among gadolinium-exposed patients with renal insufficiency: a case-control study from Denmark.

BACKGROUND: Nephrogenic systemic fibrosis (NSF) is a systemic fibrosing disease associated with exposure to gadolinium-based contrast agents (GBCA) in patients with renal insufficiency. OBJECTIVES: To report the prevalence of NSF in a well-defined cohort of patients with renal insufficiency exposed to GBCA, to investigate if GBCA-unexposed controls showed signs of NSF and to evaluate selected risk factors among NSF cases and GBCA-exposed controls. METHODS: A study among GBCA-exposed patients with renal insufficiency (n=565) was conducted to identify cases of NSF. The NSF cases found were age and sex matched and clinically compared with GBCA-exposed and unexposed patients with renal insufficiency in a case-control study. RESULTS: We identified 17 NSF cases. No signs of NSF were observed among the controls. The prevalence of NSF was 4·7%, highest among patients with chronic kidney disease (CKD) stage 5 exposed to GBCA and undergoing haemodialysis or peritoneal dialysis. Three NSF cases were identified among patients with CKD stage 3 and 4. Three patients developed NSF after macrocyclic GBCA exposure. NSF cases had a tendency to have higher serum phosphate concentrations than GBCA-exposed controls. CONCLUSIONS: Our study supports the view that GBCA is a major risk factor for NSF. Importantly, we found that patients with CKD stage 3 and 4 can be at risk of NSF. NSF may also be triggered by macrocyclic GBCA. Further, we observed a trend for higher phosphate levels in NSF cases compared with controls. The important findings drawn from this case-control study indicate that NSF is not an overlooked condition among patients with renal insufficiency not exposed to GBCA.

Systemic sclerosis and the risk of cancer: a nationwide population-based cohort study.

BACKGROUND: Earlier studies reported an increased cancer risk among patients with systemic sclerosis. Study size limitations and paucity of population-based study designs may have resulted in imprecise risk estimates. OBJECTIVES: To assess cancer risk among patients with systemic sclerosis in a nationwide follow-up study. METHODS: Patients with a first diagnosis of systemic sclerosis from 1977 to 2006 were identified from the nationwide Danish National Registry of Patients (DNRP), whose records encompass all hospitalizations and outpatient visits. Patients' DNRP records were linked to the Danish Cancer Registry. We compared their cancer incidence with that expected from cancer incidence in the general population, calculating standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). RESULTS: Two thousand and forty patients with systemic sclerosis were identified and followed for 16,003 person-years, with a median follow-up time of 6·4 years (interquartile range 2·2-11·5). Among these patients, 222 cases of cancer were identified. The overall SIR for cancer was 1·5 (95% CI 1·3-1·7), with a gender-specific SIR of 2·2 (95% CI 1·7-2·8) for men and 1·3 (95% CI 1·1-1·6) for women. The most frequent cancers were smoking- and alcohol-related cancers including lung cancer (SIR = 1·6, 95% CI 1·2-2·0), haematological cancers (SIR = 2·5, 95% CI 1·5-4·0) and immune-related cancers (SIR = 1·4, 95% CI 1·0-1·9). CONCLUSIONS: Systemic sclerosis is a risk factor for cancer, particularly smoking- and alcohol-related cancers. Men with systemic sclerosis generally are at higher cancer risk than women. Both primary and secondary cancer preventive measures are needed in the care of patients with systemic sclerosis.

Use of oral glucocorticoids and risk of skin cancer and non-Hodgkin's lymphoma: a population-based case-control study.

In North Jutland County, Denmark, we investigated whether use of oral glucocorticoids was associated with an increased risk of developing basal cell carcinoma (BCC), squamous cell carcinoma (SCC), malignant melanoma (MM), and non-Hodgkin's lymphoma (NHL). From the Danish Cancer Registry we identified 5422 BCC, 935 SCC, 983 MM, and 481 NHL cases during 1989-2003. Using risk-set sampling we selected four age- and gender-matched population controls for each case from the Civil Registration System. Prescriptions for oral glucocorticoids before diagnosis were obtained from the Prescription Database of North Jutland County on the basis of National Health Service data. We used conditional logistic regression to estimate incidence rate ratios (IRRs), adjusting for chronic medical diseases (information about these were obtained from the National Patient Registry) and use of other immunosuppressants. We found slightly elevated risk estimates for BCC (IRR, 1.15 (95% CI: 1.07-1.25)), SCC (IRR, 1.14 (95% CI: 0.94-1.39)), MM (IRR, 1.15 (95% CI: 0.94-1.41), and NHL (IRR, 1.11 (95% CI: 0.85-1.46)) among users of oral glucocorticoids. Our study supports an overall association between glucocorticoid use and risk of BCC that cannot be explained by the presence of chronic diseases or concomitant use of other immunosuppressants.

A randomized controlled trial of R-salbutamol for topical treatment of discoid lupus erythematosus.

BACKGROUND: In a recent open pilot trial, R-salbutamol sulphate, a well-known molecule with anti-inflammatory effects, was tested successfully on patients with therapy-resistant discoid lupus erythematosus (DLE). OBJECTIVES: To compare the efficacy and safety of R-salbutamol cream 0.5% vs. placebo on DLE lesions in a multicentre, double-blinded, randomized, placebo-controlled phase II trial. METHODS: Thirty-seven patients with at least one newly developed DLE lesion were randomized - 19 to the R-salbutamol cream 0.5% and 18 to placebo - and treated twice daily for 8 weeks. Efficacy was evaluated through scores of erythema, scaling/hypertrophy and induration as well as pain and itching; general improvement scored by the investigator and global improvement scored by patients' assessment were also evaluated. RESULTS: The mean area under the curve of improvement for scaling/hypertrophy, pain, itching and global patient assessment was significantly better for the actively treated patients as compared with placebo (scaling/hypertrophy, P = 0.0262; pain, P = 0.0238; itching, P = 0.0135; global patient assessment, P = 0.045). Moreover, the percentage of patients without induration was significantly higher in the active group compared with the placebo group (P = 0.013), and a statistically significantly greater decrease in the size of the lesional area was also seen in the overall analysis of the R-salbutamol-treated patients (P = 0.0197). No serious adverse events were reported. CONCLUSIONS: Application of R-salbutamol cream 0.5% was safe and well tolerated. Statistically significant effects were seen on scaling/hypertrophy, induration, pain and itching as well as patient global assessment, suggesting that R-salbutamol could be a promising new topical therapy alternative for DLE.

Use of photosensitising diuretics and risk of skin cancer: a population-based case-control study.

Diuretics have photosensitising properties. However, little is known about how these diuretics affect the risk of skin cancers. In North Jutland County, Denmark, we investigated whether the use of photosensitising diuretics was associated with an increased risk for developing basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and malignant melanoma (MM). From the cancer registry, we identified primary cases of BCC, SCC and MM during the period of 1989-2003. We selected four population controls for each case from the Danish Civil Registration System, matched on age and gender. Prescriptions for photosensitising diuretics before cancer diagnosis were ascertained in the county's Prescription Database. We used conditional logistic regression to compute incidence rate ratio (IRR), controlling for the chronic medical conditions and for the previous use of oral glucocorticoids. We found an increased risk of SCC (IRR of 1.79 (95% confidence interval (CI): 1.45-2.21)) and MM (IRR of 1.43 (95% CI: 1.09-1.88)) among users of combined amiloride and hydrochlorothiazide therapy. An increased risk of MM (IRR of 3.30 (95% CI: 1.34-8.10)) was found among users of indapamide. We found little associations with risk of BCC. Our findings provide evidence that the use of some photosensitising diuretics is associated with an increased risk for SCC and MM.

Mortality in Danish patients with nonmelanoma skin cancer, 1978-2001.

BACKGROUND: Nonmelanoma skin cancer (NMSC) is a growing public health problem among Caucasians, thus mortality data that may provide insight into the clinical course and foster our understanding of NMSC are important. OBJECTIVES: We examined total and cause-specific mortality among patients with NMSC registered in the Danish Cancer Registry from 1978 to 2001. METHODS: A total of 82 837 patients with basal cell carcinoma (BCC) and 13 453 patients with squamous cell carcinoma (SCC) were followed through the National Death Registry for specific causes of death. Standardized mortality ratios (SMRs) were computed based on mortality rates in the general population. RESULTS: Among patients with BCC, we found a slightly reduced total mortality [SMR 0.97, 95% confidence interval (CI) 0.96-0.98] with decreased SMRs seen for chronic obstructive pulmonary disease (COPD), cardiovascular disease (CVD) and diabetes mellitus. The SMR for suicide was increased. Among patients with SCC, we found an increased total mortality (SMR 1.30, 95% CI 1.26-1.33) due primarily to excess deaths from cancers, COPD, CVD and infectious diseases. CONCLUSIONS: We found markedly different mortality patterns among patients with BCC and those with SCC, suggesting important differences in the clinical course of these patients.

X-linked spondylo-epiphyseal dysplasia tarda in the Danish-Swedish farm hound.

In two litters from the same parents, three out of four males had an abnormally short leg and body length. Affected dogs showed signs of pain when moving, which could be eliminated by analgesia. On radiography, these animals had widened, radiolucent, irregularly bordered intervertebral disc spaces. When examined at seven months of age, the epiphyses appeared widened and irregular in shape and outline. General bone opacity in the vertebral column was lower in the affected male dogs than in the normal littermate. The affected dogs developed spondylosis and arthrosis of the larger limb joints. All affected dogs were euthanased on humane grounds, the eldest at the age of two years nine months. Based on the clinical and radiographic evidence, the condition seen in the male dogs described here resembles X-linked spondylo-epiphyseal dysplasia tarda caused by a collagenopathy due to malformation of COL2A1 as seen in human beings.

Mast cells and atopic dermatitis. Stereological quantification of mast cells in atopic dermatitis and normal human skin.

Stereological quantification of mast cell numbers was applied to sections of punch biopsies from lesional and nonlesional skin of atopic dermatitis patients and skin of healthy volunteers. We also investigated whether the method of staining and/or the fixative influenced the results of the determination of the mast cell profile numbers. The punch biopsies were taken from the same four locations in both atopic dermatitis patients and normal individuals. The locations were the scalp, neck and flexure of the elbow (lesional skin), and nates (nonlesional skin). Clinical scoring was carried out at the site of each biopsy. After fixation and plastic embedding, the biopsies were cut into 2 microns serial sections. Ten sections, 30 microns apart, from each biopsy were examined and stained alternately with either toluidine blue or Giemsa stain and mast cell profile numbers were determined. The study yielded the following results: (1) in atopic dermatitis lesional skin an increased number of mast cell profiles was found as compared with nonlesional skin, (2) comparing atopic dermatitis skin with normal skin, a significantly increased number of mast cell profiles per millimetre squared was found in specimens from the neck, (3) staining with toluidine blue yielded a lower number of mast cell profiles than Giemsa staining, (4) the use of Carnoy's fixative resulted in a lower mast cell profile count than the use of formaldehyde, and (5) there was no statistically significant correlation between the clinical score and the number of mast cell profiles per millimetre squared. Using stereological techniques, this study indicated that mast cells might participate in the inflammatory process in skin leading to atopic dermatitis.

Distribution of feline blood types detected in the Copenhagen area of Denmark.

The purpose of the present study was to make the first survey of the distribution of feline AB blood types in the Copenhagen area of Denmark. A total of 244 cats (139 purebred cats and 105 Domestic Shorthair cats) were tested. 93% of all tested cats had blood type A. Neither an AB nor an O type cat was detected and thus, the frequency of blood type B among all tested cats was 7%. Most type B cats were purebred cats (Birman, British Shorthair and Persian cats). No association between sex and blood type could be demonstrated among British Shorthair and Persian cats. Thus, the present study indicates that cats in Denmark predominantly have blood type A, and that blood type B cats are rare, except for certain breeds such as Birman and British Shorthair cats.

Atopic dermatitis and birth factors: historical follow up by record linkage.

OBJECTIVE: To study if factors at birth are associated with later development of atopic dermatitis. DESIGN: Historical follow up by record linkage from Danish medical birth register. Children were followed up for 5.5 to 8.5 years. Second historical follow up study comprising questionnaire to mothers of singleborn children 6.5 to 9.5 years after birth. SETTING: Private dermatology clinics and dermatology and paediatric departments in the municipality of Aarhus, Denmark. SUBJECTS: 7862 singletons born in hospital between 1 January 1984 and 31 December 1986 to mothers living in the municipality of Aarhus. Questionnaires sent to 985 mothers. MAIN OUTCOME MEASURES: Gestational age, birth weight, parity, and age of mother at the time of birth. Atopy in children diagnosed by specialists in dermatology and physicians. Family size; diagnosis of atopic dermatitis, allergic rhinitis, and asthma; family predisposition; and mothers' smoking habits during pregnancy determined from questionnaires. RESULTS: Of 7862 children, 403 were diagnosed as having atopic dermatitis by a specialist; the cumulative incidence at age 7 was 5.6%. High gestational age and low parity were associated with an increased risk of atopic dermatitis. Among 985 children atopic dermatitis had been diagnosed by any physician in 184; the cumulative incidence at age 7 was 18.7%. High birth weight, high gestational age, and family history of atopy were associated with increased risk of atopic dermatitis. CONCLUSION: In both studies the incidence of atopic dermatitis was associated with high gestational age and in one with high birth weight also. The causes for these associations are at present unknown but may indicate that even during gestation factors associated with atopic dermatitis influence maturation.

Wheezing, asthma, hayfever, and atopic eczema in childhood following exposure to tobacco smoke in fetal life.

BACKGROUND: Prenatal maternal smoking has been associated with adverse respiratory effects in childhood such as lung deficits and wheezing, but results concerning asthma, hayfever, and atopic eczema are inconsistent. OBJECTIVE: In the present study, we investigate the effects of maternal smoking in pregnancy on asthma, hayfever, atopic eczema, and wheezing in the offspring up to the age of 14-18. METHODS: The study was based on a cohort of mothers enrolled during midwife visits around the 36th week of gestation in Odense and Aalborg, Denmark, 1984-1987. Singleton, live born children (n = 11,144) were followed-up in 2002 to obtain a childhood history of atopic diseases, by means of questionnaires to the parents. Multivariate logistic regression analyses for medical diagnoses of asthma, hayfever, atopic eczema, and symptoms of wheezing before the age of 3, were carried out on 7844 children. RESULTS: After adjustment for confounders, late prenatal smoke exposure was associated with wheezing, with an odds ratio (OR) of 1.2, and a 95% confidence interval (CI) of 1.1-1.5. Furthermore, slightly reduced estimates for hayfever (OR 0.8, CI 0.7-1.0) and atopic eczema (OR 0.8, CI 0.7-0.9) were obtained for children exposed in late pregnancy compared with non-exposed. CONCLUSION: Late gestational smoke exposure was associated with wheezing but not with asthma, while null or even protective estimates were indicated for hayfever and atopic eczema. However, lack of control options for hereditary factors may have affected the results.