Modern Rheumatology
ISSN: 1439-7595 (Print) 1439-7609 (Online) Journal homepage: http://www.tandfonline.com/loi/imor20
CINCA syndrome with surgical intervention for valgus deformity and flexion contracture of the knee joint: A case report Yuki Harada, Kenichi Fukiage, Ryuta Nishikomori, Shigeo Suzuki & Tohru Futami To cite this article: Yuki Harada, Kenichi Fukiage, Ryuta Nishikomori, Shigeo Suzuki & Tohru Futami (2015): CINCA syndrome with surgical intervention for valgus deformity and flexion contracture of the knee joint: A case report, Modern Rheumatology To link to this article: http://dx.doi.org/10.3109/14397595.2015.1040609
Accepted author version posted online: 13 Apr 2015. Published online: 13 Jun 2015. Submit your article to this journal
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Date: 05 November 2015, At: 23:41
http://informahealthcare.com/mor ISSN 1439-7595 (print), 1439-7609 (online) Mod Rheumatol, 2015; Early Online: 1–3 © 2015 Japan College of Rheumatology DOI: 10.3109/14397595.2015.1040609
CASE REPORT
CINCA syndrome with surgical intervention for valgus deformity and flexion contracture of the knee joint: A case report Yuki Harada1, Kenichi Fukiage1, Ryuta Nishikomori2, Shigeo Suzuki3, and Tohru Futami2 1Department of Pediatric Orthopaedics, Shiga Medical Center for Children, Shiga, Japan, 2Department of Pediatrics, Kyoto University Hospital,
Downloaded by [Washington University in St Louis] at 23:41 05 November 2015
Shiga, Japan, and 3Department of Pediatric Orthopaedics, Mizuno Memorial Hospital, Shiga, Japan
Abstract
Keywords
Chronic infantile neurological, cutaneous, and articular (CINCA) syndrome is a systemic autoinflammatory disease caused by increased production of interleukin (IL)-1b. We present a case of CINCA syndrome followed up to skeletal maturity. Joint contracture and valgus deformity of the knee had developed before diagnosis. Surgical interventions by soft tissue release and hemiepiphysiodesis improved the contracture and the deformity, and IL-1 receptor antagonist dramatically controlled systemic inflammation, and the patient lives without any disabilities.
CINCA syndrome, Flexion contracture, Hemiepiphysiodesis, IL-1 beta inhibitor
Introduction Chronic infantile neurological, cutaneous, and articular (CINCA) syndrome is a severe chronic inflammatory disease of early onset, characterized by cutaneous symptoms, central nervous system involvement, and arthropathy [1]. The associated quality of life is often poor and the functional prognosis depends on the occurrence of joint contractures resulting from the early-onset arthropathies. However, this rare condition is difficult to diagnose because it sometimes mimics other autoinflammatory diseases such as juvenile idiopathic arthritis (JIA) [2]. Although only a hundred cases have been reported worldwide, this syndrome is increasingly recognized by pediatricians. However, to our knowledge, there have been no reports on CINCA syndrome regarding orthopedic aspects. In this paper, we report a case of CINCA syndrome in which severe musculoskeletal disorders were treated surgically and followed up until maturity for over 10 years.
Case report A 1 year and 10 months old boy presented with a limp and repetitive fever, and was diagnosed with JIA at the age of 2 years and 6 months. Increased intracranial pressure and ocular tension, as well as pigmentation on his face, were also confirmed. Treatment using oral non-steroidal anti-inflammatory drugs was started, although they were not effective. Systemic inflammation continued, even after initiating oral corticosteroid and methotrexate. Flexion contractures in his bilateral knees were exacerbated up to 70°, leading to a non-ambulatory state at the age of 9 years. Overgrowth of bilateral distal femoral epiphyses, especially on the medial side, was observed on a radiogram (Figure 1a–c). Correspondence to: Yuki Harada, Department of Pediatric Orthopaedics, Shiga Medical center for children, 5-7-30 Moriyama, Moriyama city, Shiga, 524-0022, Japan. Tel: 81-77-582-6200. Fax: 81-77-582-6304. E-mail: [email protected]
History Received 7 October 2014 Accepted 7 April 2015 Published online 15 June 2015
On one occasion, the knee contractures were slightly improved by physiotherapy, although they again deteriorated (Figure 2). Posterior soft tissue release for bilateral knees was performed; in detail, gastrocnemius muscle tendon, iliotibial tract, biceps femoris muscle tendon, posterior cruciate ligament, and medial hamstrings were released, and the posterior half of the medial collateral ligament, fibular collateral ligament, and joint capsule were also released. Neurovascular tightness obstructed additional improvement, and the flexion contracture was improved to 30° (Figure 2). After casting for 2 weeks, slow and gentle range of motion (ROM) exercise was performed by continuous passive motion for 5 weeks. The patient could walk with a long leg brace at the time of discharge, and with a knee brace 6 months later. Use of a night brace was continued for 12 months to avoid recurrent flexion contracture. At the age of 12, he presented with a limited ROM in bilateral elbows. However, no treatment was administered because the disability in activities of daily living (ADL) was mild. Overgrowth of bilateral humeral lateral condyles and varus deformity of the elbows was then observed on a radiogram. Around this time, he was diagnosed with CINCA syndrome by genetic analyses and somatic nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) mosaicism was detected. However, interleukin-1 (IL-1) receptor antagonist was not available in our country. ROM of the knee and elbow was maintained by physiotherapy. When he was 14 years old, anakinra, an IL-1 receptor antagonist, was administered and his systemic inflammation was dramatically improved. Joint contracture of the knees and elbows gradually improved (Figure 2). The disabilities in ADL also improved. Residual bony deformity induced valgus deformity of bilateral knees (Figure 3a), and hemiepiphysiodesis was performed for the right medial distal femur at the age of 17 years. The hemiepiphysiodesis was performed with medial approach under general anesthesia. The physis of the distal femur was confirmed with fluoroscope, and the growth plate on the medial side was
2 Y. Harada et al.
Mod Rheumatol, 2015; Early Online: 1–3
Downloaded by [Washington University in St Louis] at 23:41 05 November 2015
Figure 1. Plain radiographs of the knee in anteroposterior (AP) view (a) and lateral view (b, c) at the age of 9 years. The radiographs in AP view (d) and lateral view (e, f) at the age of 19 years.
partially resected with the sharp curettes. The surgery resulted in the medial growth arrest in the distal femur, and the asymmetrical growth corrected the valgus deformity gradually (Figure 3c). The mechanical axis passed zone 2 in the right knee and zone 1 in the left one at final follow-up after bony maturation, although leg length discrepancy (LLD) of 2.5 cm remained (Figure 3b). Sufficient ROM was maintained, even with femoral and humeral deformities (Figure 1d–f), and there was no disability in ADL at final follow-up after bony maturation. Anakinra was changed to canakinumab [3], a human immunoglobulin G or IgG monoclonal antibody targeting IL-1b, and systemic inflammation was still well controlled. The patient was fully informed that his data would be submitted for publication, and he gave his consent.
Discussion CINCA syndrome was first described in 1963 by Walshe et al. [4]. It is defined as an autoinflammatory disease and also one of the cryopyrin-associated periodic syndromes, which includes area spectrum of autoinflammatory diseases caused by mutations of NLRP3/cold-induced autoinflammatory syndrome 1 (CIAS1),
Figure 2. Clinical course of the flexion contracture of the knee. Filled circle: right knee, filled square: left knee. Single arrow: the age when soft tissue release was performed. Double arrow: the age when administration of IL-1 receptor antagonist started.
including familial cold autoinflammatory syndrome, familial cold urticaria, and Muckle–Wells syndrome [5]. In terms of medical treatment in recent years, CINCA syndrome has been reported to be successfully treated by IL-1 receptor antagonist [6–8]. It is, however, difficult to diagnose because it sometimes mimics other autoinflammatory diseases such as JIA. Surgical intervention is controversial for conditions with systemic inflammation because operative treatment should be considered when the primary disease is well controlled with medication [9]. However, in this case, not only conservative treatment but also operative treatment was necessary because of the disability due to the natural course of the disease. We showed that aggressive posterior soft tissue release for the joint contracture and subsequent intensive physiotherapy were efficient to maintain functional extremities during prolonged diagnostic intervals. Subsequent continuous passive motion exercise was important as post-operative treatment in our case with uncontrolled systemic inflammation. If the joint contracture is left untreated, irreversible joint contracture and severe bony deformity would occur. There should be no hesitation to perform surgical intervention to avoid permanent disorders in the extremities. As a limitation, we cannot assess the effect of anakinra on the severe joint contractures without surgical intervention. There are no definite criteria for diagnosing CINCA syndrome, which sometimes mimics other autoinflammatory diseases. Unfortunately, the diagnosis in our case was delayed. Thus, genetic diagnosis of NLRP3/CIAS1 gene mutation is important, although the mutation is positive in only 60% of CINCA syndrome patients. Negative cases were indicated to have heterogeneous mutation in somatic cells, so genetic diagnosis should be carefully performed [10]. Several types of skin lesion are observed in 75% of the patients, and inflammation of the optic nerve and central nervous system is another characteristic [2]. Overgrowth of the patella and distal femur creates a prominence of the knees that is characteristic of CINCA syndrome [1]. For early diagnosis, genetic diagnosis for CINCA syndrome should be considered if the standard treatment for JIA is ineffective. The recent development of biological therapy enabled essential treatment of CINCA syndrome, and IL-1 receptor antagonist and
CINCA syndrome with surgical intervention 3
DOI 10.3109/14397595.2015.1040609
we recommend the preceding medication for autoinflammation before surgical intervention. There are a few reports describing the clinical course of CINCA syndrome and related autoinflammatory diseases until adulthood [16]. This report shows the natural course of bony deformity with uncontrolled systemic inflammation caused by CINCA syndrome. Our rare case followed up to skeletal maturity could be helpful for considering surgical intervention.
Conflicts of interest None.
Downloaded by [Washington University in St Louis] at 23:41 05 November 2015
References
Figure 3. Clinical course of the valgus deformity of the knee. (a) The radiograph of right knee before hemiepiphysiodesis at the age of 17 years. (b) The radiograph at the age of 22 years. (c) Valgus angle of right knee before and after hemiepiphysiodesis.
antibody targeting IL-1b [11,12] are drugs that can be used based on the pathogenesis. In our case, the drug was approved in our country when the patient was aged 14 years, when bony deformities had already progressed. Even in such a difficult status, residual knee contracture was improved by IL-1 receptor antagonist regardless of the joint deformities, and targeted therapy should be started as soon as possible. Chronic inflammation around the knee has been reported to induce both acceleration of growth and temporary growth arrest. LLD is often found in young patients with unilateral arthritis [13], and valgus deformity of the knee is found in patients with general arthritis. LLD is usually adjusted within 2 years after remission of the joint inflammation, and valgus deformity is also corrected, whereas severe deformity did not improve before physeal closure [14]. In these cases, guided growth such as hemiepiphysiodesis and stapling/plating is effective [15]. Fortunately, in our case, the relatively late hemiepiphysiodesis corrected the valgus deformity because the growth potential restored in the distal femur was enough for improving the deformity. It is uncertain that the medication restored the growth potential and prolonged the age of skeletal maturity. The valgus deformity persisted at the latest follow-up, and corrective osteotomy in the lower extremity was indicated, but the patient did not wish another surgical treatment because he could do everything in daily life without pain. It is difficult to predict a child’s growth with systemic inflammation, and
1. Sugiura H, Matsubayashi T. Clinical features of CINCA syndrome: Effects and problems of IL-1Ra (in Japanese). Nihon Rinsho Meneki Gakkai Kaishi. 2007;30(2):108–13. 2. Aoyama K, Amano H, Takaoka Y, Nishikomori R, Ishikawa O. Cryopyrin-associated periodic syndrome: A case report and review of the Japanese literature. Acta Derm Venereol. 2012;92(4):395–8. 3. Jasmin BK, Eduardo R, Norbert B, Joachim R, Sandra DF, Thomas J, et al. Canakinumab (ACZ885, a fully human IgG1 antiIL-1b mAb) induces sustained remission in pediatric patients with cryopyrin-associated periodic syndrome (CAPS). Arthritis Res Ther. 2011;13(1):R34. doi: 10.1186/ar3266. 4. Walshe MM,Warin RP. Syndrome of prolonged history of evanescent blotchy urticaria associated with arthritis, hepatosplenomegaly and lymphadenopathy(Still’s disease). Proc R Soc Med. 1963;56(10):905–6. 5. Goldbach-Mansky R. Current status of understanding the pathogenesis and management of patients with NOMID/CINCA. Curr Rheumatol Rep. 2011;13(2):123–31. 6. Miyamae T, Inaba Y, Nishimura G, Kikuchi M, Kishi T, Hara R, et al. Effect of anakinra on arthopathy in CINCA/NOMID syndrome. Pediatr Rheumatol Online J. 2010;8:6. doi: 10.1186/1546-0096-8-9. 7. Kuemmerle-Deschner JB, Tyrrell PN, Koetter I, Wittkowski H, Bialkowski A, Tzaribachev N, et al. Efficacy and safety of Anakinra therapy in pediatric and adult patients with autoinflammatory MuckleWells syndrome. Arthritis Rheum. 2011;63(3):840–9. 8. Sibley CH, Plass N, Snow J, Wiggs EA, Brewer CC, King KA, et al. Sustained response and prevention of damage progression in patients with neonatal-onset multisystem inflammatory disease treated with anakinra: A cohort study to determine three- and five-year outcomes. Arthritis Rheum. 2012;64(7):2375–86. 9. Goodman SM, Fiffie M. Lower extremity arthroplasty in patients with inflammatory arthrisis: Preoperative and perioperative managemant. J Am Acad Othop Surg. 2013;21(6):355–63. 10. Tanaka N, Izawa K, Saito MK, Sakuma M, Oshima K, Ohara O, et al. High incidence of NLRP3 somatic mosaicism in patients with chronic infantile neurologic, cutaneous, articular syndrome: Results of an international multicenter collaborative study. Arthritis Rheum. 2011;63(11):3625–32. 11. Caorsi R, Lepore L, Zulian F, Alessio M, Stabile A, Insalaco A, et al. The schedule of administration of canakinumab in cryopyrin associated periodic syndrome is driven by the phenotype severity rather than the age. Arthritis Res Ther. 2013;15(1):R33. doi: 10.1186/ar4184. 12. Kone-Paut I, Lachmann HJ, Kuemmerle-Deschner JB, Hachulla E, Leslie KS, Mouy R, et al. Sustained remission of symptoms and improved health-related quality of life in patients with cryopyrinassociated periodic syndrome treated with canakinumab: Results of a double-blind placebo-controlled randomized withdrawal study. Arthritis Res Ther. 2011;13(6):R202. doi: 10.1186/ar3535. 13. Simon S, Whiffen J, Shapiro F. Leg-length discrepancies in monoarticular and pauciarticular juvenile rheumatoid arthritis. J Bone Joint Surg Am. 1981;63(2):209–15. 14. Sherry DD, Stein LD, Reed AM, Schanberg LE, Kredich DW. Prevention of leg length discrepancy in young children with pauciarticular juvenile rheumatoid arthritis by treatment with intraarticular steroids. Arthritis Rheum.1999;42(11):2330–4. 15. Rydholm U, Brattstrom H, Bylander B, Lidgren L. Stapling of the knee in juvenile chronic arthritis. J Pediatr Orthop. 1987;7(1):63–8. 16. Posch C, Kaulfersch W, Rappersberger K. Cryopyrin-Associated Periodic Syndrome. Pediatr Dermatol. 2014;31(2):228–31. doi: 10.1111/j.1525–1470.2012.01812.x.
ISSN: 1439-7595 (Print) 1439-7609 (Online) Journal homepage: http://www.tandfonline.com/loi/imor20
CINCA syndrome with surgical intervention for valgus deformity and flexion contracture of the knee joint: A case report Yuki Harada, Kenichi Fukiage, Ryuta Nishikomori, Shigeo Suzuki & Tohru Futami To cite this article: Yuki Harada, Kenichi Fukiage, Ryuta Nishikomori, Shigeo Suzuki & Tohru Futami (2015): CINCA syndrome with surgical intervention for valgus deformity and flexion contracture of the knee joint: A case report, Modern Rheumatology To link to this article: http://dx.doi.org/10.3109/14397595.2015.1040609
Accepted author version posted online: 13 Apr 2015. Published online: 13 Jun 2015. Submit your article to this journal
Article views: 9
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=imor20 Download by: [Washington University in St Louis]
Date: 05 November 2015, At: 23:41
http://informahealthcare.com/mor ISSN 1439-7595 (print), 1439-7609 (online) Mod Rheumatol, 2015; Early Online: 1–3 © 2015 Japan College of Rheumatology DOI: 10.3109/14397595.2015.1040609
CASE REPORT
CINCA syndrome with surgical intervention for valgus deformity and flexion contracture of the knee joint: A case report Yuki Harada1, Kenichi Fukiage1, Ryuta Nishikomori2, Shigeo Suzuki3, and Tohru Futami2 1Department of Pediatric Orthopaedics, Shiga Medical Center for Children, Shiga, Japan, 2Department of Pediatrics, Kyoto University Hospital,
Downloaded by [Washington University in St Louis] at 23:41 05 November 2015
Shiga, Japan, and 3Department of Pediatric Orthopaedics, Mizuno Memorial Hospital, Shiga, Japan
Abstract
Keywords
Chronic infantile neurological, cutaneous, and articular (CINCA) syndrome is a systemic autoinflammatory disease caused by increased production of interleukin (IL)-1b. We present a case of CINCA syndrome followed up to skeletal maturity. Joint contracture and valgus deformity of the knee had developed before diagnosis. Surgical interventions by soft tissue release and hemiepiphysiodesis improved the contracture and the deformity, and IL-1 receptor antagonist dramatically controlled systemic inflammation, and the patient lives without any disabilities.
CINCA syndrome, Flexion contracture, Hemiepiphysiodesis, IL-1 beta inhibitor
Introduction Chronic infantile neurological, cutaneous, and articular (CINCA) syndrome is a severe chronic inflammatory disease of early onset, characterized by cutaneous symptoms, central nervous system involvement, and arthropathy [1]. The associated quality of life is often poor and the functional prognosis depends on the occurrence of joint contractures resulting from the early-onset arthropathies. However, this rare condition is difficult to diagnose because it sometimes mimics other autoinflammatory diseases such as juvenile idiopathic arthritis (JIA) [2]. Although only a hundred cases have been reported worldwide, this syndrome is increasingly recognized by pediatricians. However, to our knowledge, there have been no reports on CINCA syndrome regarding orthopedic aspects. In this paper, we report a case of CINCA syndrome in which severe musculoskeletal disorders were treated surgically and followed up until maturity for over 10 years.
Case report A 1 year and 10 months old boy presented with a limp and repetitive fever, and was diagnosed with JIA at the age of 2 years and 6 months. Increased intracranial pressure and ocular tension, as well as pigmentation on his face, were also confirmed. Treatment using oral non-steroidal anti-inflammatory drugs was started, although they were not effective. Systemic inflammation continued, even after initiating oral corticosteroid and methotrexate. Flexion contractures in his bilateral knees were exacerbated up to 70°, leading to a non-ambulatory state at the age of 9 years. Overgrowth of bilateral distal femoral epiphyses, especially on the medial side, was observed on a radiogram (Figure 1a–c). Correspondence to: Yuki Harada, Department of Pediatric Orthopaedics, Shiga Medical center for children, 5-7-30 Moriyama, Moriyama city, Shiga, 524-0022, Japan. Tel: 81-77-582-6200. Fax: 81-77-582-6304. E-mail: [email protected]
History Received 7 October 2014 Accepted 7 April 2015 Published online 15 June 2015
On one occasion, the knee contractures were slightly improved by physiotherapy, although they again deteriorated (Figure 2). Posterior soft tissue release for bilateral knees was performed; in detail, gastrocnemius muscle tendon, iliotibial tract, biceps femoris muscle tendon, posterior cruciate ligament, and medial hamstrings were released, and the posterior half of the medial collateral ligament, fibular collateral ligament, and joint capsule were also released. Neurovascular tightness obstructed additional improvement, and the flexion contracture was improved to 30° (Figure 2). After casting for 2 weeks, slow and gentle range of motion (ROM) exercise was performed by continuous passive motion for 5 weeks. The patient could walk with a long leg brace at the time of discharge, and with a knee brace 6 months later. Use of a night brace was continued for 12 months to avoid recurrent flexion contracture. At the age of 12, he presented with a limited ROM in bilateral elbows. However, no treatment was administered because the disability in activities of daily living (ADL) was mild. Overgrowth of bilateral humeral lateral condyles and varus deformity of the elbows was then observed on a radiogram. Around this time, he was diagnosed with CINCA syndrome by genetic analyses and somatic nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) mosaicism was detected. However, interleukin-1 (IL-1) receptor antagonist was not available in our country. ROM of the knee and elbow was maintained by physiotherapy. When he was 14 years old, anakinra, an IL-1 receptor antagonist, was administered and his systemic inflammation was dramatically improved. Joint contracture of the knees and elbows gradually improved (Figure 2). The disabilities in ADL also improved. Residual bony deformity induced valgus deformity of bilateral knees (Figure 3a), and hemiepiphysiodesis was performed for the right medial distal femur at the age of 17 years. The hemiepiphysiodesis was performed with medial approach under general anesthesia. The physis of the distal femur was confirmed with fluoroscope, and the growth plate on the medial side was
2 Y. Harada et al.
Mod Rheumatol, 2015; Early Online: 1–3
Downloaded by [Washington University in St Louis] at 23:41 05 November 2015
Figure 1. Plain radiographs of the knee in anteroposterior (AP) view (a) and lateral view (b, c) at the age of 9 years. The radiographs in AP view (d) and lateral view (e, f) at the age of 19 years.
partially resected with the sharp curettes. The surgery resulted in the medial growth arrest in the distal femur, and the asymmetrical growth corrected the valgus deformity gradually (Figure 3c). The mechanical axis passed zone 2 in the right knee and zone 1 in the left one at final follow-up after bony maturation, although leg length discrepancy (LLD) of 2.5 cm remained (Figure 3b). Sufficient ROM was maintained, even with femoral and humeral deformities (Figure 1d–f), and there was no disability in ADL at final follow-up after bony maturation. Anakinra was changed to canakinumab [3], a human immunoglobulin G or IgG monoclonal antibody targeting IL-1b, and systemic inflammation was still well controlled. The patient was fully informed that his data would be submitted for publication, and he gave his consent.
Discussion CINCA syndrome was first described in 1963 by Walshe et al. [4]. It is defined as an autoinflammatory disease and also one of the cryopyrin-associated periodic syndromes, which includes area spectrum of autoinflammatory diseases caused by mutations of NLRP3/cold-induced autoinflammatory syndrome 1 (CIAS1),
Figure 2. Clinical course of the flexion contracture of the knee. Filled circle: right knee, filled square: left knee. Single arrow: the age when soft tissue release was performed. Double arrow: the age when administration of IL-1 receptor antagonist started.
including familial cold autoinflammatory syndrome, familial cold urticaria, and Muckle–Wells syndrome [5]. In terms of medical treatment in recent years, CINCA syndrome has been reported to be successfully treated by IL-1 receptor antagonist [6–8]. It is, however, difficult to diagnose because it sometimes mimics other autoinflammatory diseases such as JIA. Surgical intervention is controversial for conditions with systemic inflammation because operative treatment should be considered when the primary disease is well controlled with medication [9]. However, in this case, not only conservative treatment but also operative treatment was necessary because of the disability due to the natural course of the disease. We showed that aggressive posterior soft tissue release for the joint contracture and subsequent intensive physiotherapy were efficient to maintain functional extremities during prolonged diagnostic intervals. Subsequent continuous passive motion exercise was important as post-operative treatment in our case with uncontrolled systemic inflammation. If the joint contracture is left untreated, irreversible joint contracture and severe bony deformity would occur. There should be no hesitation to perform surgical intervention to avoid permanent disorders in the extremities. As a limitation, we cannot assess the effect of anakinra on the severe joint contractures without surgical intervention. There are no definite criteria for diagnosing CINCA syndrome, which sometimes mimics other autoinflammatory diseases. Unfortunately, the diagnosis in our case was delayed. Thus, genetic diagnosis of NLRP3/CIAS1 gene mutation is important, although the mutation is positive in only 60% of CINCA syndrome patients. Negative cases were indicated to have heterogeneous mutation in somatic cells, so genetic diagnosis should be carefully performed [10]. Several types of skin lesion are observed in 75% of the patients, and inflammation of the optic nerve and central nervous system is another characteristic [2]. Overgrowth of the patella and distal femur creates a prominence of the knees that is characteristic of CINCA syndrome [1]. For early diagnosis, genetic diagnosis for CINCA syndrome should be considered if the standard treatment for JIA is ineffective. The recent development of biological therapy enabled essential treatment of CINCA syndrome, and IL-1 receptor antagonist and
CINCA syndrome with surgical intervention 3
DOI 10.3109/14397595.2015.1040609
we recommend the preceding medication for autoinflammation before surgical intervention. There are a few reports describing the clinical course of CINCA syndrome and related autoinflammatory diseases until adulthood [16]. This report shows the natural course of bony deformity with uncontrolled systemic inflammation caused by CINCA syndrome. Our rare case followed up to skeletal maturity could be helpful for considering surgical intervention.
Conflicts of interest None.
Downloaded by [Washington University in St Louis] at 23:41 05 November 2015
References
Figure 3. Clinical course of the valgus deformity of the knee. (a) The radiograph of right knee before hemiepiphysiodesis at the age of 17 years. (b) The radiograph at the age of 22 years. (c) Valgus angle of right knee before and after hemiepiphysiodesis.
antibody targeting IL-1b [11,12] are drugs that can be used based on the pathogenesis. In our case, the drug was approved in our country when the patient was aged 14 years, when bony deformities had already progressed. Even in such a difficult status, residual knee contracture was improved by IL-1 receptor antagonist regardless of the joint deformities, and targeted therapy should be started as soon as possible. Chronic inflammation around the knee has been reported to induce both acceleration of growth and temporary growth arrest. LLD is often found in young patients with unilateral arthritis [13], and valgus deformity of the knee is found in patients with general arthritis. LLD is usually adjusted within 2 years after remission of the joint inflammation, and valgus deformity is also corrected, whereas severe deformity did not improve before physeal closure [14]. In these cases, guided growth such as hemiepiphysiodesis and stapling/plating is effective [15]. Fortunately, in our case, the relatively late hemiepiphysiodesis corrected the valgus deformity because the growth potential restored in the distal femur was enough for improving the deformity. It is uncertain that the medication restored the growth potential and prolonged the age of skeletal maturity. The valgus deformity persisted at the latest follow-up, and corrective osteotomy in the lower extremity was indicated, but the patient did not wish another surgical treatment because he could do everything in daily life without pain. It is difficult to predict a child’s growth with systemic inflammation, and
1. Sugiura H, Matsubayashi T. Clinical features of CINCA syndrome: Effects and problems of IL-1Ra (in Japanese). Nihon Rinsho Meneki Gakkai Kaishi. 2007;30(2):108–13. 2. Aoyama K, Amano H, Takaoka Y, Nishikomori R, Ishikawa O. Cryopyrin-associated periodic syndrome: A case report and review of the Japanese literature. Acta Derm Venereol. 2012;92(4):395–8. 3. Jasmin BK, Eduardo R, Norbert B, Joachim R, Sandra DF, Thomas J, et al. Canakinumab (ACZ885, a fully human IgG1 antiIL-1b mAb) induces sustained remission in pediatric patients with cryopyrin-associated periodic syndrome (CAPS). Arthritis Res Ther. 2011;13(1):R34. doi: 10.1186/ar3266. 4. Walshe MM,Warin RP. Syndrome of prolonged history of evanescent blotchy urticaria associated with arthritis, hepatosplenomegaly and lymphadenopathy(Still’s disease). Proc R Soc Med. 1963;56(10):905–6. 5. Goldbach-Mansky R. Current status of understanding the pathogenesis and management of patients with NOMID/CINCA. Curr Rheumatol Rep. 2011;13(2):123–31. 6. Miyamae T, Inaba Y, Nishimura G, Kikuchi M, Kishi T, Hara R, et al. Effect of anakinra on arthopathy in CINCA/NOMID syndrome. Pediatr Rheumatol Online J. 2010;8:6. doi: 10.1186/1546-0096-8-9. 7. Kuemmerle-Deschner JB, Tyrrell PN, Koetter I, Wittkowski H, Bialkowski A, Tzaribachev N, et al. Efficacy and safety of Anakinra therapy in pediatric and adult patients with autoinflammatory MuckleWells syndrome. Arthritis Rheum. 2011;63(3):840–9. 8. Sibley CH, Plass N, Snow J, Wiggs EA, Brewer CC, King KA, et al. Sustained response and prevention of damage progression in patients with neonatal-onset multisystem inflammatory disease treated with anakinra: A cohort study to determine three- and five-year outcomes. Arthritis Rheum. 2012;64(7):2375–86. 9. Goodman SM, Fiffie M. Lower extremity arthroplasty in patients with inflammatory arthrisis: Preoperative and perioperative managemant. J Am Acad Othop Surg. 2013;21(6):355–63. 10. Tanaka N, Izawa K, Saito MK, Sakuma M, Oshima K, Ohara O, et al. High incidence of NLRP3 somatic mosaicism in patients with chronic infantile neurologic, cutaneous, articular syndrome: Results of an international multicenter collaborative study. Arthritis Rheum. 2011;63(11):3625–32. 11. Caorsi R, Lepore L, Zulian F, Alessio M, Stabile A, Insalaco A, et al. The schedule of administration of canakinumab in cryopyrin associated periodic syndrome is driven by the phenotype severity rather than the age. Arthritis Res Ther. 2013;15(1):R33. doi: 10.1186/ar4184. 12. Kone-Paut I, Lachmann HJ, Kuemmerle-Deschner JB, Hachulla E, Leslie KS, Mouy R, et al. Sustained remission of symptoms and improved health-related quality of life in patients with cryopyrinassociated periodic syndrome treated with canakinumab: Results of a double-blind placebo-controlled randomized withdrawal study. Arthritis Res Ther. 2011;13(6):R202. doi: 10.1186/ar3535. 13. Simon S, Whiffen J, Shapiro F. Leg-length discrepancies in monoarticular and pauciarticular juvenile rheumatoid arthritis. J Bone Joint Surg Am. 1981;63(2):209–15. 14. Sherry DD, Stein LD, Reed AM, Schanberg LE, Kredich DW. Prevention of leg length discrepancy in young children with pauciarticular juvenile rheumatoid arthritis by treatment with intraarticular steroids. Arthritis Rheum.1999;42(11):2330–4. 15. Rydholm U, Brattstrom H, Bylander B, Lidgren L. Stapling of the knee in juvenile chronic arthritis. J Pediatr Orthop. 1987;7(1):63–8. 16. Posch C, Kaulfersch W, Rappersberger K. Cryopyrin-Associated Periodic Syndrome. Pediatr Dermatol. 2014;31(2):228–31. doi: 10.1111/j.1525–1470.2012.01812.x.
