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There is an increasing consensus that the treatment of Hidradenitis suppurativa (HS) significantly varies with the degree of inflammation and that treatment according to guidelines is not always successful. Here, we report the case of a 31-year-old male with widespread, highly inflammatory Hurley Stage II HS in multiple locations who failed to respond to any kind of established medical treatment, including biologics. As an alternative approach, Ustekinumab was maintained, and additionally the patient was treated with LAight therapy, a combination of intense pulsed light and radiofrequency. After 10 sessions, deroofing of multiple lesions was performed in a two-step process. After a few weeks of healing time accompanied by specialized wound experts, the patient continued with LAight therapy to control and prevent recurrence. This case shows that the combination of LAight therapy and deroofing is a promising treatment plan for the long-term symptom control of mild and moderate HS.

NEMO-deficient patients present with variable degrees of immunodeficiency. Accordingly, treatment ranges from antibiotic prophylaxis and/or IgG-substitution to allogenic hematopoietic stem cell transplantation (HSCT). The correct estimation of the immunodeficiency is essential to avoid over- as well as under-treatment. We compare the immunological phenotype of a NEMO-deficient patient with a newly-described splice site mutation that causes truncation of the NEMO zinc-finger (ZF) domain and a severe clinical course with the immunological phenotype of three NEMO-deficient patients with missense mutations and milder clinical courses and all previously published patients. Lymphocyte subsets, proliferation, and intracellular NEMO-expression were assessed by FACS. NF-κB signal transduction was determined by measuring IκBα-degradation and the production of cytokines upon stimulation with TNF-α, IL-1β, and TLR-agonists in immortalized fibroblasts and whole blood, respectively. The patient with truncated ZF-domain of NEMO showed low levels of IgM and IgG, reduced class-switched memory B cells, almost complete skewing towards naive CD45RA+ T cells, impaired T cell proliferation as well as cytokine production upon stimulation with TNF-α, IL-1β, and TLR-agonists. He suffered from severe infections (sepsis, pneumonia, osteomyelitis) during infancy. In contrast, three patients with missense mutations in IKBKG presented neither skewing of T cells towards naivety nor impaired T cell proliferation. They are stable on prophylactic IgG-substitution or even off any prophylactic treatment. The loss of the ZF-domain and the impaired T cell proliferation accompanied by almost complete persistence of naive T cells despite severe infections are suggestive for a profound immunodeficiency. Allogenic HSCT should be considered early for these patients before chronic sequelae occur.

Background Methotrexate (MTX) intolerance is a frequent problem of long-term treatment in juvenile idiopathic arthritis (JIA). Mutations in the methylentetrahydrofolate reductase (MTHFR) gene may increase toxicity of MTX, potentially constituting an initial stimulus for this conditioned response. The objective of this study was to investigate the relationship of common MTHFR gene mutations and occurrence of MTX intolerance in pediatric patients with JIA treated with MTX. Methods Consecutive JIA patients on at least 3 months of MTX treatment were included in this study. Intolerance to MTX was determined using the Methotrexate Intolerance Severity Score (MISS) questionnaire, and MTX intolerance was defined as MISS values of ≥ 6. Presence of the two most common mutations in the MTHFR gene (C677T and A1298C) was tested using a PCR assay. Results were analyzed using descriptive and non-parametric statistics. Results 196 patients were included (73 % female). Of those, 93 (46 %) showed MTX intolerance. 168 patients were genotyped for C677T and A1298C. MTX intolerance was not found to be significantly more frequent among patients with hetero- and homozygous or homozygous mutations C677T or A1298C compared to wild type or heterozygous mutations. Analysis of the correlation between numbers of mutations in these two loci to the MISS score did not yield a statistically significant correlation. Conclusion Mutations in the MTHFR gene were not found to be significantly more frequent in JIA patients intolerant to MTX. Toxicity associated with the MTHFR gene seems to result from mechanisms different to those involved in clinical MTX intolerance. Electronic supplementary material The online version of this article (doi:10.1186/s12969-016-0071-y) contains supplementary material, which is available to authorized users.

Table S3. Demographic and clinical data of study participants; patients where MTHFR testing was available. Table S4. Influence of demographic and clinical data on MTX intolerance; patients where MTHFR testing was available. (DOCX 35 kb)

Methotrexate (MTX) is the cornerstone disease-modifying anti-rheumatic drug (DMARD) in juvenile idiopathic arthritis (JIA). In Dutch patients, MTX intolerance occurred frequently and was associated with subcutaneous (SC) administration. The aim of this study was to assess the prevalence of MTX intolerance and its association with the route of administration in a German cohort of JIA patients.A cross-sectional study of JIA patients on MTX was performed. Primary outcome was MTX intolerance, which was determined using the validated Methotrexate Intolerance Severity Score (MISS) questionnaire. The prevalence of gastrointestinal adverse effects and MTX intolerance was compared between patients on MTX SC and MTX administered orally (PO).Of 179 JIA patients on MTX, 73 (40.8%) were intolerant. The odds of MTX intolerance were higher in patients using MTX exclusively SC compared to exclusively PO (adjusted odds ratio 3.37 [95% confidence interval 1.19-10.0]). There was strong evidence that the former experienced more behavioural complaints (76.1% vs. 47.4%, p=0.001) and weak evidence that they experienced more abdominal pain after MTX intake (43.5% vs. 27.4%, p=0.056).The prevalence of MTX intolerance was high and exclusively SC administration of MTX was associated with MTX intolerance and behavioural adverse effects. The prevalence of gastrointestinal adverse effects was at least as high as in patients on MTX PO. The frequently held assumption that SC causes fewer side effects than PO seems unwarranted. Definite answers about the differences between SC and PO administration with respect to safety and efficacy should be obtained by randomised trials.

Objectives A high proportion of children with JIA will develop intolerance to MTX with anticipatory and associative gastrointestinal adverse effects. Parents and physicians frequently try to alleviate these symptoms with a variety of countermeasures. The objective of this study was to investigate the course of MTX intolerance within a 6 month period, and the effects of countermeasures on MTX intolerance severity. Methods We performed a prospective study of 196 consecutive JIA patients treated with MTX. Intolerance was determined using the Methotrexate Intolerance Severity Score (MISS) questionnaire. MISS and countermeasures instituted by parents or physicians were determined at four time points, each 2 months apart. Countermeasures, classified into four types (antiemetic drugs, covert dosing, taste masking and complementary medicine), were analysed using non-parametric statistics and mixed linear modelling, adjusted by propensity scoring for use of countermeasures. Results Ninety patients (46%) showed MTX intolerance, with 58 (64%) using countermeasures at time of inclusion. Median MISS at inclusion was 11 (interquartile range = 8.0-14.25), and did not change significantly over time. No significant difference in MISS score was observed between patients receiving countermeasures and those who did not. For specific countermeasures, MISS did not change significantly after introduction. Sensitivity analysis adjusting for propensity score indicated no significant association of MISS severity on parents' decision to implement any countermeasures. Conclusion MTX intolerance was present in many children with JIA and symptoms decreased little in the short term. Various modalities used as countermeasures against nausea by parents showed no discernible effect.

Einleitung: Methotrexat (MTX) ist das meistverwendete Medikament zur Therapie der Juvenilen idiopathischen Arthritis (JIA). Die Therapie führt jedoch häufig zu einer Intoleranz, gekennzeichnet durch ein ausgeprägtes Ekelgefühl, die die weitere Therapie erschwert und teilweise zu [for full text, please go to the a.m. URL], 42. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 28. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 24. wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)

Einleitung: Methotrexat (MTX) ist das meistverwendete Medikament zur Therapie der Juvenilen Idiopathischen Arthritis. Die Therapie führt jedoch häufig zu einer Intoleranz, gekennzeichnet durch ein ausgeprägtes Ekelgefühl und Verweigerung der Einnahme. Mutationen im Gen für Methylentetrahydrofolatreduktase[for full text, please go to the a.m. URL], 42. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 28. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 24. wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)

Background Methotrexate (MTX) is the drug used most frequently in the therapy of juvenile idiopathic arthritis (JIA). However, long-term treatment in children frequently leads to intolerance, with marked revulsion and refusal of treatment. Mutations in the gene for methylenetetrahydrofolate reductase (MTHFR) can lead to increased toxicity of MTX and could possibly represent an initial stimulus for this conditioned response. Objectives The objective of this study was to investigate the relation of common mutations in the MTHFR gene and occurrence of MTX intolerance in pediatric patients with juvenile idiopathic arthritis treated with MTX. Methods Consecutive patients admitted to the German Center for Pediatric and Adolescent Rheumatology from October 2012 until April 2014 included in this study. Inclusion criteria were 1) diagnosis of JIA and 2) treatment with MTX for at least 3 months prior to inclusion. Exclusion criteria were other diseases leading to nausea and/or abdominal complaints, and concomitant medications possibly inducing nausea (excepting biologics and non-steroidal anti-inflammatory drugs). Intolerance to MTX was determined using the validated Methotrexate Intolerance Severity Score (MISS) questionnaire; presence of MTX intolerance was assumed for MISS values of ≥6. Presence of the two most common mutations in the MTHFR gene (C677T and A1298C) was tested using a polymerase chain reaction assay, as described previously. Results were analyzed using descriptive statistics and chi square testing. Results 114 patients were included (71% female, age at inclusion (median) 12.6 years, disease duration (median) 4.1 years). Of those, 49 (43%) showed MTX intolerance. 42% of patients were heterozygous, and 7% homozygous for the C677T mutation of the MTHFR gene, 45% of patients were heterozygous, and 12% homozygous for the A1298C mutation; both are comparable to published allele frequencies. Compared to the homozygous wild type, MTX intolerance was not found significantly more frequent in patients with hetero- and homozygous (p=1.000) or homozygous (p=0.125) C677T mutations, nor in patients with hetero- and homozygous (p=0.775) or homozygous (p=0.444) A1298C mutations. Compound heterozygous mutations for C677T and A1298C were also not found significantly more frequently in patients with MTX intolerance (p=0.809). Conclusions Mutations in the MTHFR gene are not found significantly more frequently in JIA patients with intolerance to MTX. Toxicity associated with the MTHFR gene does not seem to be causally related to the development of MTX intolerance. Acknowledgements This study was supported by the “Stiftung Hilfe fur das rheumakranke Kind e.V.” Disclosure of Interest None declared

Background Methotrexate (MTX) is the mainstay treatment in the therapy of children with juvenile idiopathic arthritis (JIA) and can lead to prolonged remission and improved quality of life. However JIA patients frequently develop intolerance to MTX, with anticipatory and associative gastrointestinal adverse effects before drug intake, arising as a conditioned response. Parents frequently try to alleviate these symptoms with a variety of countermeasures against nausea. Objectives The objective of this study was to investigate the course of MTX intolerance in pediatric patients over a period of 6 months, as well as the effect of countermeasures by parents on the severity of MTX intolerance. Methods Consecutive patients admitted to the German Center for Pediatric and Adolescent Rheumatology from October 2012 until April 2014 were included in this study. MTX intolerance was measured using the validated Methotrexate Intolerance Severity Score (MISS) questionnaire. Inclusion criteria were 1) diagnosis of JIA, 2) treatment with MTX for at least 3 months prior to inclusion, and 3) confirmation of MTX intolerance by a MISS value of ≥6. Exclusion criteria were other diseases leading to nausea and/or abdominal complaints, and concomitant medications possibly inducing nausea (excepting biologics and non-steroidal anti-inflammatory drugs). Methotrexate dose, MISS and countermeasures instituted by the parents were determined at 4 time points (at inclusion, at 6 weeks, 3 months and 6 months). Countermeasures were classified into 4 criteria: antiemetic drugs, covert dosing, taste masking and complementary medicine. Results were analyzed using descriptive statistics and non-parametric testing (Wilcoxon signed rank test). Results 38 patients were included (63% female, median age at inclusion 11.7 years, median disease duration 7.1 years). Average MISS at inclusion was 10.8±4.1, and after 6 months 12.2±7.2 (p=0.316). In 6/38 patients (16%), MTX was reduced or discontinued during the study. In 89 time intervals between study visits, 40 countermeasures were introduced by the parents. Conclusions If MTX intolerance is present, symptoms will not decrease over the course of 6 months. Various modalities used by the parents as countermeasures against nausea by the parents show no discernible effect. Acknowledgements This study was supported by the “Stiftung Hilfe fur das rheumakranke Kind e.V.” Disclosure of Interest None declared