Objective Pulmonary involvement in chronic nonbacterial osteomyelitis (CNO) is rare. Limited awareness results in diagnostic challenges, especially because malignancy or infection needs to be considered. Methods Based on a survey shared among centers participating in the Kerndokumentation Deutsches Rheumaforschungszentrum (Germany), this study investigated clinical and imaging presentations, demographic features, treatment response and outcomes of pulmonary involvement in CNO (pCNO). Magnetic resonance imaging and computed tomography images were read centrally by an experienced pediatric radiologist. Results Twenty‐two patients with pCNO were included in this study. Among patients with CNO, pulmonary involvement was more common in girls (91% vs 62.8%, P = 0.006) and patients with multifocal bone lesions (95% vs 65%, P <0.001) but was not associated with systemic inflammation or additional organ involvement. Forty‐two pulmonary lesions were counted with a median of two per patient (two to six). They displayed a median size of 1.8 cm (0.3–4.0 cm) and followed mono‐ (40%) and oligo‐focal (60%) patterns representing consolidations or nodules, abutting the pleura in 50%. Although prominent hilar lymph nodes were present (in 19% of patients), no pathologic enlargement (>1 cm) was seen. When available (3 of 22 patients), histology revealed granulomatous inflammation with lymphocyte infiltration. Development and courses of pCNO did not associate with treatments chosen. Complete remission was reported in 60% of patients, partial remission in 20%. Conclusion pCNO is usually asymptomatic. Although more common in girls and patients with multifocal CNO, pCNO is not associated with systemic parameters of inflammation or specific organ involvement. Prognosis of pCNO is favorable, and most lesions resolve over time. Thus, a careful watch‐and‐wait strategy may be appropriate.

Protracted febrile myalgia syndrome (PFMS) is a rare manifestation of familial Mediterranean fever (FMF), characterized by myalgia, fever and elevated inflammatory markers lasting several weeks. As the hallmark of FMF are short episodes of disease symptoms, the long duration of PFMS may lead to a delayed diagnosis and treatment. 1. To perform a review of literature and rheumatology textbooks focused on clinical features and treatment of PFMS in children. 2. To present our own case. All articles in Pub Med generated using the keywords “protracted febrile myalgia” and information on PFMS in seven rheumatology textbooks were collected. The systematic review was supplemented with our own case presentation. In total, 18 articles with 78 pediatric patients (including our own) were retrieved. More than half of the patients presented with PFMS as the first manifestation of FMF. All complained of myalgia, 65

Wir präsentieren 2 Patientinnen, die sich beide mit einer einseitigen Lidschwellung und Ptosis vorstellten.

Bei der bislang gesunden 7-jährigen Patientin aus Nigeria wurde in der Augenklinik bei beidseitiger granulomatöser Uveitis der Verdacht auf eine Tuberkulose geäußert und sie der Kinderrheumatologie zugewiesen. Bei der Patientin kam es bereits vor einem Monat aufgrund einer alternierenden Fazialisparese und Artikulationsstörungen in einer auswärtigen Klinik zu einer stationären Aufnahme. Seit dem Beginn der Symptomatik hatte die Patientin beidseitig gerötete Augen ohne Schmerzen oder Visusminderung. Die Eltern bemerkten zudem eine sich verschlechternde Hypakusis. Initial hatte sie einmalig Fieber ohne weitere systemische Symptome. Anamnestisch bestand keine organische oder anorganische Antigenexposition, keine Hausrenovierung erinnerlich.

Abstract Background Cogan´s syndrome is a rare, presumed autoimmune vasculitis of various vessels characterized by interstitial keratitis and vestibular impairment accompanied by sensorineural hearing loss. Due to the rarity of Cogan´s syndrome in children, therapeutic decision making may be challenging. Therefore, a literature search was performed to collect all published paediatric Cogan´s syndrome cases with their clinical characteristics, disease course, treatment modalities used and their outcome. The cohort was supplemented with our own patient. Main text Altogether, 55 paediatric Cogan´s syndrome patients aged median 12 years have been reported so far. These were identified in PubMed with the keywords “Cogan´s syndrome” and “children” or “childhood”. All patients suffered from inflammatory ocular and vestibulo-auditory symptoms. In addition, 32/55 (58%) manifested systemic symptoms with musculoskeletal involvement being the most common with a prevalence of 45%, followed by neurological and skin manifestations. Aortitis was detected in 9/55 (16%). Regarding prognosis, remission in ocular symptoms was attained in 69%, whereas only 32% achieved a significant improvement in auditory function. Mortality was 2/55. Our patient was an 8 year old girl who presented with bilateral uveitis and a history of long standing hearing deficit. She also complained of intermittent vertigo, subfebrile temperatures, abdominal pain with diarrhoea, fatigue and recurrent epistaxis. The diagnosis was supported by bilateral labyrinthitis seen on contrast-enhanced magnetic resonance imaging. Treatment with topical and systemic steroids was started immediately. As the effect on auditory function was only transient, infliximab was added early in the disease course. This led to a remission of ocular and systemic symptoms and a normalization of hearing in the right ear. Her left ear remained deaf and the girl is currently evaluated for a unilateral cochlear implantation. Conclusions This study presents an analysis of the largest cohort of paediatric Cogan´s syndrome patients. Based on the collected data, the first practical guide to a diagnostic work-up and treatment in children with Cogan´s syndrome is provided.

Die Diagnose einer juvenilen idiopathischen Arthritis basiert auf dem Vorliegen einer persistierenden Arthritis nach sorgfältigem Ausschluss anderer Erkrankungen. Im vorliegenden Fall berichten wir über eine Patientin, bei der es bereits im Alter von 4 Monaten zu einer ausgeprägten Polyarthritis gekommen ist. Laborchemisch zeigten sich eine Anämie, eine Thrombozytose bei normalen Leukozyten, eine Hypergammaglobulinämie und erhöhte Entzündungswerte. Bei anhaltender Symptomatik wurde unter der Verdachtsdiagnose einer seronegativen Polyarthritis eine kurzdauernde Therapie mit Steroiden und MTX begonnen. Dies zeigte nur wenig Effekt. Im weiteren Verlauf entwickelte das Mädchen ein Exanthem im Gesichts- und Brustbereich. Aufgrund der ungewöhnlich frühen Manifestation einer schweren therapierefraktären Polyarthritis wurde eine molekulargenetische Untersuchung veranlasst (whole-exome sequencing – WES). Hierbei konnte eine Variante im CTLA4-Gen (CTLA4 c.416 A > G; p.Tyr139Cys heterozygot) nachgewiesen werden, welche als pathogenetisch relevant eingestuft wurde. Unter dem initialen Therapieversuch mit Abatacept kam es zu keiner wesentlichen Besserung der Symptomatik. Daraufhin Umstellung auf Rituximab. Nachdem auch hierunter keine ausreichende Verbesserung eintrat, musste eine Stammzelltransplantation durchgeführt werden. Seither ist das Mädchen klinisch beschwerdefrei.

ZUSAMMENFASSUNGEinleitung: Das Kawasaki-Syndrom (KS) ist eine systemische Vaskulitis, die mittelgroße Arterien betrifft. Obwohl Diagnose- und Klassifizierungskriterien existieren, kann die Abgrenzung von anderen Krankheiten schwierig sein.Falldarstellung: Bei einer 3-jährigen Patientin wurden neben Fieber folgende Symptome und Befunde festgestellt: Konjunktivitis, zervikale Lymphadenopathie, Palmarschwellung, gerötete und rissige Lippen sowie ein makulöses Exanthem. Diese Befunde sind mit einem kompletten KS vereinbar. Die Urin-PCR auf Leptospiren war positiv. Nach 2 Wochen entwickelte sich eine periunguale Schuppung.Diskussion: Dieser Fall zeigt, dass eine Leptospirose nicht nur ähnliche Symptome wie das KS aufweist, sondern auch mit dieser Erkrankung assoziiert sein kann. Dafür sprechen spezifische Befunde wie Schuppungen an Fingern, Zehen und Veränderungen der oropharyngealen Schleimhäute.

Das 10-jährige türkischstämmige Mädchen wurde aus einer auswärtigen Klinik übernommen mit hohem Fieber seit 2 Wochen sowie heftigen Bauchschmerzen. Es war eine Appendektomie durchgeführt worden, mikroskopisch zeigte die Appendix eine lymphofollikuläre Invasion mit der histologischen Diagnose einer katarrhalischen Appendizitis. Intraoperativ wurde eine ausgeprägte Lymphadenitis mesenterialis mit Enteritis und Aszites beschrieben. Zu den weiterhin persistierenden Bauchschmerzen klagte das Mädchen über ausgeprägte multitope Myalgien und Arthralgien. Im Alter von 3 Jahren war eine Purpura Schönlein-Henoch (PSH) durchgemacht worden. 2 Wochen vor der Erkrankung trat eine Rachenentzündung ohne Erregernachweis auf.

Das Mädchen habe schon immer viel getragen werden müssen, ein Ablegen des Säuglings war auch im schlafenden Zustand nur kurz möglich gewesen. Ab dem 4. Lebensmonat war es kurzzeitig zu einer leichten Besserung der Symptomatik gekommen. Nun vermuteten die Eltern erneut Schmerzen in den Beinen. Fieber war bisher nicht aufgetreten. In den vom niedergelassenen Kinderarzt veranlassten Laboruntersuchungen wurde ein erhöhtes C-reaktives Protein (CRP) von 8,7 mg/dl (Normwert < 0,3 mg/ dk) und ein erniedrigtes Hämoglobin (Hb) von 9,3 g/dl (Normwert 10,7–13,1 g/dl) festgestellt.

Background: Kawasaki disease (KD) is a systemic vasculitis which affects medium-sized arteries. Although diagnostic and classification criteria exist, differentiation from other diseases can be difficult. Case Presentation: We present a 3-year old patient with a diagnosis of complete KD with positivity for urine-PCR on leptospirosis. In our patient conjunctivitis, rash, fever, cervical lymphadenopathy, palmar swelling, exanthema were seen, indicating all criteria for complete KD. After 2 weeks periungual desquamation developed. Besides this patient two further cases were retrieved form the literature with similar clinical courses indicating leptospirosis associated KD. Conclusion: These cases indicate that leptospirosis may not only mimic but also be associated with KD shown by specific findings like desquamation of fingers, toes and oropharyngeal mucous membrane changes. To distinguish between KD, leptospirosis and leptospirosis associated KD a proper history taking including travel history and contact to animals is fundamental as well as thorough clinical and cardiac examinations in the course of the disease. While diagnostic procedures and observation might take time, treatment of acute KD should not be delayed.

Deficiency of interleukin-36 receptor antagonist (DITRA) is a life threatening monogenic autoinflammatory disease caused by loss of function mutations in the IL36RN gene. Affected patients develop recurrent episodes of generalized pustular psoriasis (GPP) with systemic inflammation and fever. We here review and analyze the literature on pediatric DITRA patients who have been treated by biologicals targeting inflammatory cytokines. A database research was performed to identify all relevant articles on pediatric DITRA patients treated with biologicals. According to defined response criteria therapeutic efficacy was analyzed. Our literature research revealed 12 pediatric patients with DITRA who have received treatment with biologicals and we add a further not yet reported patient. Out of these 13 patients 10 were homozygous including 6 with the p.Leu27Pro, 3 with the p.Arg10 Argfs* and 1 with the p.Thr123Met mutation. 3 patients were compound heterozygous. In total 28 flares were treated with biological agents- targeting IL-1, IL-17, IL-12/23 and TNF-α. Complete response was achieved in 16 flares (57%), a partial reponse was seen in 2 flares (7%), and no response was observed in 10 flares (36%). Response rates were heterogeneous among the different agents. While complete/partial/no response with inhibition of TNF-alpha could be achieved in 7 (58%)/1 (8%)/4 (33%), the inhibition of IL-17 and of IL-12/23 led in each 4 flares to a 100% complete response. IL-1 inhibition led to complete/partial response in each 1 (13%) and was not effective in 6 (76%) flares. Of note, the novel patient was successfully treated with weekly dosed adalimumab. DITRA is a rare disease that has to be considered in GPP with systemic inflammation and fever. It can be effectively treated with specific biological inhibition of TNF-alpha, IL-12/23 and IL- 17, while anti-IL-1 treatment seems less effective. Weekly dosed adalimumab appears to be a treatment option for pediatric patients. Further reports and studies of biological treated pediatric DITRA patients are warranted for evaluation of optimal treatment.

Background Deficiency of interleukin-36 receptor antagonist (DITRA) is a life threatening autoinflammatory disease caused by autosomal recessive mutations of the IL36RN gene leading to recurrent episodes of generalized pustular psoriasis with systemic inflammation and fever. The disease is rare and no standardized treatment guidelines exist Objectives To systematically review and analyze the literature on biologically treated pediatric DITRA patients Methods A NCBI pubmed database research was performed to identify all relevant articles on pediatric DITRA patients treated with biologicals. According to defined response criteria therapeutic efficacy was analyzed. Results Our literature research revealed 13 pediatric patients with DITRA and biolocial treatment. Ten patients were homozygous including six with the p.Leu27Pro, three with the p.Arg10 Argfs* and one with the p.Thr123Met mutation and three were compound heterozygous. We add an unreported DITRA patient with a compound heterozygous IL36RN p.Pro76Leu/pSer113Leu mutation. In total 29 flares in 14 patients were treated with biological agents- targeting IL-1/R, IL-17, IL-12/23 and TNF-α. Complete response was achieved in 15 (52%), partial in 4 (14%), and no response in 10 (34%) of the flares. Response rates were heterogeneous among the different agents. While complete/partial/no response with inhibition of TNF-alpha could be achieved in 6 (46%)/3 (23%)/4 (31%), the inhibition of IL-17 and of IL-12/23 led in each 4 flares to a 100% complete response. IL-1/R inhibition led to complete/partial response in each 1 (13%) and was not effective in 6 (75%) flares. Of note, the unreported patient was successfully treated with weekly dosed adalimumab. Conclusion DITRA is a rare disease that has to be considered in patients with generalized pustular psoriasis with systemic inflammation and fever. It can be effectively treated with specific biological inhibition of TNF-alpha, IL-12/23 and IL- 17, while anti-IL-1/R treatment seems less effective. Weekly dosed adalimumab appears to be a novel treatment option for pediatric patients. Further reports and studies of biological treated pediatric DITRA patients are warranted for evaluation of optimal treatment. Reference [1] Marrakchi, S., P. Guigue, et al. (2011). "Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis." N Engl J Med 365(7): 620-628. Disclosure of Interests Toni Hospach Speakers bureau: Chugai, Roche, Novartis, Fabian Glowatzki: None declared, Friederike Blankenburg: None declared, Dennis Conzelmann: None declared, Christian Strinkorb: None declared, Chris Sandra Muellerschoen: None declared, Peter Driesch von den: None declared, Lisa Koehler: None declared, Meino Rohlfs: None declared, Christoph Klein: None declared, Fabian Hauck: None declared