Growth Retardation in Non-steroid Treated Juvenile Rheumatoid Arthritis

Polito, Cesare; Strano, C. G.; Olivieri, Alma Nunzia; Alessio, Maria; Iammarrone, Clemente Servodio; Todisco, Nicola; Papale, Massimo

doi:10.3109/03009749709115826

Cited by 49 publications

(40 citation statements)

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“…Furthermore, growth impairment has been reported in systemic and polyarticular JIA patients never treated with corticosteroids (Polito et al 1997). This indicates that other factors, not only GCs, contribute to the deleterious effects of chronic inflammation on bone growth.…”

Section: Impact Of Gc Treatment On Bone Growthmentioning

confidence: 99%

RECENT RESEARCH ON THE GROWTH PLATE: Impact of inflammatory cytokines on longitudinal bone growth

Sederquist¹,

Fernandez-Vojvodich²,

Zaman³

et al. 2014

Journal of Molecular Endocrinology

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Children with inflammatory diseases usually display abnormal growth patterns as well as delayed puberty. This is a result of several factors related to the disease itself, such as malnutrition, hypercortisolism, and elevated levels of pro-inflammatory cytokines. These factors in combination with glucocorticoid treatment contribute to growth retardation during chronic inflammation by systemically affecting the major regulator of growth, the GH/IGF1 axis. However, recent studies have also shown evidence of a direct effect of these factors at the growth plate level. In conditions of chronic inflammation, pro-inflammatory cytokines are upregulated and released into the circulation. The most abundant of these, tumor necrosis factor a, interleukin 1b (IL1b), and IL6, are all known to directly act on growth plate cartilage to induce apoptosis and thereby suppress bone growth. Both clinical and experimental studies have shown that growth retardation can partly be rescued when these cytokines are blocked. Therefore, therapy modulating the local actions of these cytokines may be effective for preventing growth failure in patients with chronic inflammatory disorders. In this review, we report the current knowledge of inflammatory cytokines and their role in regulating bone growth.

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Section: Impact Of Gc Treatment On Bone Growthmentioning

confidence: 99%

RECENT RESEARCH ON THE GROWTH PLATE: Impact of inflammatory cytokines on longitudinal bone growth

Sederquist¹,

Fernandez-Vojvodich²,

Zaman³

et al. 2014

Journal of Molecular Endocrinology

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“…11 Polito ve ark., hastalığın süresinin uzamasının ve daha yüksek düzeyde iş-levsel tutulumun büyüme hızında gerileme için risk faktörleri olduğunu göstermişlerdir. 25 Bizim çalışmamızda ise IL-6 düzeyleri ve uzun süreli hastalık arasında istatistiksel olarak anlamlı bir ilişki bulunmamıştır.…”

Section: Discussionunclassified

“…18,19 Polito ve ark., hiç steroid tedavisi almamış hastalarda da uzamanın etkilendiğini bildirmişlerdir. 25 Diğer çalışma-lar da dikkate alındığında, JİA'lı çocuklarda uzama hızını korumada kortikosteroidlerden kaçınmak kadar inflamasyonun agresif kontrolünün de önemli olduğu düşünülmektedir. …”

Section: Discussionunclassified

Interleukin-6 Concentrations and Growth Velocity in Juvenil Idiopathic Arthritis

Yıldırım¹,

Çakar²,

Kızılgün³

et al. 2015

Turkiye Klinikleri J Pediatr

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Ö ÖZ ZE ET T A Am ma aç ç: : Jüvenil idiyopatik artrit (JİA) hastalarında büyüme hızının inflamasyon bulguları, hastalık aktivasyonu, interlökin-6 (IL-6) ve tedavi ile olan ilişkisini araştırmaktır. G Ge er re eç ç v ve e Y Yö ön nt te em ml le er r: : Çalışmaya 64 JİA tanılı hasta alındı. İnaktif hastalık ve klinik remisyon kriterleri, başlangıçta ve izlem süresince Wallace ve ark.nın belirlediği kriterlere göre saptandı. Antropometrik veriler Dünya Sağ-lık Örgütü standartlarına göre değerlendirildi. Büyüme hızı (cm/6 ay), başlangıç ve altı ay sonraki öl-çümler arası farkın geçen süreye bölünmesi ile hesaplandı. Değerler kronolojik yaşa göre standart sapma (Z skoru) şeklinde ifade edildi. Z skoru -2 SD altındaki değerler düşük uzama hızı olarak tanımlandı. Eritrosit sedimentasyon hızı (ESH) ≥20 mm/saat, C-reaktif protein (CRP) ≥1 mg/dL ve serum IL-6 düzeyi ≥17 pg/mL değerleri artmış olarak değerlendirildi. Hastaların yaşları, cinsiyetleri, hastalık başlangıç yaşları, ortalama takip süreleri, hastalık alt tipleri ve aldıkları tedaviler kaydedildi. Klinik ve laboratuvar değerlendirme ilk değerlendirmeden altı ay sonra tekrarlandı. B Bu ul lg gu ul la ar r: : Otuz üç (%51,6) hasta kız, 31 (%48,4) hasta erkek cinsiyette idi. Hastalık tiplerine göre en fazla oligoartiküler JİA bulundu (n=27; %42,2). Aktif hastalık dönemlerinde ESH, CRP ve IL-6 değerleri yüksek olarak saptandı. Düşük büyüme hızı sıklığı %23,4 idi; glukokortikoid tedavisi ve uzun süreli hastalık ile iliş-kili bulundu. Serum ESH, CRP ve IL-6 düzeyleri büyüme hızı ile ilişkili bulunmadı. S So on nu uç ç: : JİA tanılı hastalarda düşük büyüme hızı sıklığı yüksektir. Hastalarımızda düşük büyüme hızı literatürle benzer şekilde bulunmuştur. Hastaların izleminde kullanılan inflamasyon parametrelerinin hâlâ önemini koruduğu, hastalığın aktivite belirteci olarak IL-6 düzeyinin de anlamlı olduğu sonucuna varılmıştır. Bu hastalarda glukokortikoid maruziyeti büyüme üzerine olumsuz etkili ana faktör gibi görünmektedir.A An na ah ht ta ar r K Ke el li im me el le er r: : Artrit, jüvenil romatoid; büyüme; interlökin-6 A AB BS ST TR RA AC CT T O Ob bj je ec ct ti iv ve e: : To evaluate associations of growth velocity with inflammatory markers, dise-ase activity, interleukin-6 (IL-6) levels and treatments in patients with juvenile idiopathic arthritis (JIA). M Ma at te er ri ia al l a an nd d M Me et th ho od ds s: : Sixty four patients with JIA participated in the study. Inactive disease and clinical remission criterias were determined at baseline assessment and during the follow up according to criteria of Wallace et al. Anthropometric data were classified according to the World Health Organization standards. Growth velocity (cm/6 months) was defined by the difference between baseline and 6 months later measures, divided by follow up time. Values was expressed as standard deviation (Z score) according to chronological age. Values below the Z score ≤-2 were considered low growth velocity. Erythrocyte sedimentation rate (ESR) ≥20 mm/h, C-reactive protein (CRP) ≥1 mg/dL...

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“…They often have a prolonged course, accompanied by growth retardation, which has a psychological influence on adolescents. 3,11,12 Although rGH therapy is attempted, only a few reports have stated that rGH injection is effective for treating growth retardation in children with severe JRA. 13 Furthermore, rGH therapy was shown to be ineffective in a patient taking corticosteroids (PDN Ͼ0.35 mg/kg per day).…”

Section: Discussionmentioning

confidence: 99%

Intense immunosuppression followed by purified blood CD34+ cell autografting in a patient with refractory juvenile rheumatoid arthritis

Nakagawa

Kawano

Yoshimura

et al. 2001

Bone Marrow Transplant

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Summary:A 15-year-old boy with refractory juvenile rheumatoid arthritis (JRA) underwent intense immunosuppressive therapy followed by purified blood CD34+ cell autografting. He had been taking prednisolone (PDN) daily or every other day combined with methotrexate once a week to control the disease for 7 years. He suffered from psychological complications and a very short stature due to the adverse effects of these drugs. CD34+ cells were purified in bulk from G-CSF-mobilized PBSC using an Isolex 300. After the administration of cyclophosphamide (200 mg/kg) and anti-lymphocyte globulin (45 mg/kg), 3.6 × 10 6 /kg purified CD34 + cells were infused. His post-transplant course was uneventful except for herpes-zoster infection. He is now more than 1 year post transplant and has not taken any immunosuppressive medication. His rate of growth has increased (Ͼ10 cm/year) due to the effects of the cessation of PDN and the administration of recombinant human growth hormone (rGH), in contrast to the gain of 2 cm in the preceding 3 years with rGH treatment. Although the durability of this remission is unknown, intense immunosuppressive therapy followed by purified blood CD34+ cell autografting might be acceptable for adolescent patients with refractory JRA to achieve a drug-free period for physical and psychological maturation. Bone Marrow Transplantation (2001) 27, 333-336. Keywords: juvenile rheumatoid arthritis; growth retardation; purified blood CD34 + cell autografting; recombinant human growth hormone Juvenile rheumatoid arthritis (JRA) is one of the most common rheumatic diseases of children and a major cause of chronic disability.1-3 Although JRA is not always fatal, except in a small proportion of patients with systemic disease, it often becomes refractory to combinations of non- steroidal anti-inflammatory drugs (NSAIDs) or immunosuppressive drugs such as methotrexate (MTX), cyclophosphamide (CY), and corticosteroids. In such cases, patients are susceptible to severe joint destruction and various adverse effects from long-term treatment, and adolescent patients often must endure a mental and physical burden. To improve the quality of life in these patients, a new strategy with intense immunosuppression followed by stem cell support has been introduced, first for patients with fatal autoimmune disease, and then for those with non-fatal disease that is refractory to ordinary therapies. [4][5][6][7] We report here a 15 year-old boy with refractory JRA who was treated with high-dose CY and anti-lymphocyte globulin (ALG) followed by purified blood CD34 + cell autografting. Case reportThe patient was a 15-year-old boy. In October 1992, at the age of 8, he developed high-grade fever and multiple arthralgia. Since his symptoms failed to respond to antibiotics prescribed by a general practitioner, he was referred to the Department of Pediatrics of Tokushima Municipal Hospital. The laboratory examinations revealed acceleration of the erythrocyte sedimentation rate (102 mm/h) and elevation of C-reactive protein (14.5 mg/dl) a...

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Growth Retardation in Non-steroid Treated Juvenile Rheumatoid Arthritis

Cited by 49 publications

References 1 publication

RECENT RESEARCH ON THE GROWTH PLATE: Impact of inflammatory cytokines on longitudinal bone growth

RECENT RESEARCH ON THE GROWTH PLATE: Impact of inflammatory cytokines on longitudinal bone growth

Interleukin-6 Concentrations and Growth Velocity in Juvenil Idiopathic Arthritis

Intense immunosuppression followed by purified blood CD34+ cell autografting in a patient with refractory juvenile rheumatoid arthritis

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