Noriko Kinjo

Clinical and laboratory features of fatal rapidly progressive interstitial lung disease associated with juvenile dermatomyositis

OBJECTIVE Rapidly progressive interstitial lung disease (RP-ILD) is a rare but potentially fatal complication of JDM. The aim of this study was to establish markers for the prediction and early diagnosis of RP-ILD associated with JDM. METHODS The clinical records of 54 patients with JDM were retrospectively reviewed: 10 had RP-ILD (7 died, 3 survived), 19 had chronic ILD and 24 were without ILD. Routine tests included a high-resolution CT (HRCT) scan of the chest and measurement of serum levels of creatine phosphokinase, ferritin and Krebs von den Lungen-6 (KL-6). Anti-melanoma differentiation-associated gene 5 (MDA5) antibodies and IL-18 levels were measured by ELISA. RESULTS No differences were found in the ratio of juvenile clinically amyopathic DM between the three groups. Initial chest HRCT scan findings were variable and could not distinguish between RP-ILD and chronic ILD. Anti-MDA5 antibodies were positive in all 8 patients with RP-ILD and 10 of 14 with chronic ILD, but none of the patients without ILD. Serum levels of anti-MDA5 antibody, ferritin, KL-6 and IL-18 were significantly higher in the RP-ILD group than in the chronic ILD and non-ILD groups. Serum levels of IL-18 positively correlated with serum KL-6 (R = 0.66, P < 0.001). CONCLUSION High serum levels of IL-18, KL-6, ferritin and anti-MDA5 antibodies (e.g. >200 units by ELISA) are associated with RP-ILD. These can be used as an indication for early intensive treatment. Both alveolar macrophages and autoimmunity to MDA5 are possibly involved in the development of RP-ILD associated with JDM.

Cardiovascular effects of Acanthaster planci venom in the rat: Possible involvement of PAF in its hypotensive effect

Cardiovascular effects of the crowns-of-thorns starfish (Acanthaster planci) venom were examined in rats. The crude venom extracted from the spines of A. planci caused systemic hypotension associated with an increase in heart rate and a decrease in renal cortical blood flow when given i.v. The hypotensive effect of the venom was not inhibited by pretreatment with atropine, indomethacin or aprotinin, but was significantly inhibited by SRI 63-441, a platelet activating factor (PAF) antagonist. The venom caused dose-dependent vasorelaxation of the isolated rat aortic ring preparation precontracted by noradrenaline, an effect which was significantly attenuated by pretreatment with SRI 63-441, methylene blue or parabromophenacyl bromide. Denudation of the endothelium also diminished the vasorelaxing effect of the venom. Both the vasorelaxing and the hypotensive effects showed tachyphylaxis. These results suggest the release of PAF or a PAF-like substance from the endothelium by the venom.

Serum IL-18 as a potential specific marker for differentiating systemic juvenile idiopathic arthritis from incomplete Kawasaki disease

Abstract Clinical features and laboratory parameters in patients with incomplete Kawasaki disease (KD) and systemic juvenile idiopathic arthritis (s-JIA) tend to overlap. Furthermore, there have been no definite biomarkers for these diseases. This situation makes the clinical diagnosis of these patients difficult. In this study, we aimed to measure serum interleukin (IL)-18 and IL-6 levels in patients with s-JIA who were initially diagnosed with incomplete KD and compare these data with those in patients with complete KD and arthritis. Serum IL-18 levels in patients with s-JIA were significantly elevated compared with those in patients with KD and arthritis. Pediatricians should be aware that the presentation of s-JIA can mimic incomplete KD. Because the clinical features overlap, a high index of suspicion is warranted. The measurement of serum IL-18 may be useful for differentiating s-JIA from KD.

Application of personal computer to an analysis of small de novo chromosomal insertion: A case of de novo 3q2 trisomy with ins(8;3)

SummaryTo identify the origin of a small inserted segment in a de novo 8p+ chromosome, an originally programmed computerized data-base for chromosomal aberration syndromes was utilized. The system selected 3q2 trisomy and 10q2 trisomy as candidates. As a result of a careful comparison of several high-resolution banding patterns among chromosomes 3, 10 and the inserted segment, her karyotype was disignated as: 46,XX,−8,+der(8), inv ins(8;3)(p21.1;q26.32q24) de novo. A small segment from 3q24 to 3q26.32 was trisomic, and invertedly inserted into the short arm of chromosome 8. This computerized database was considered to be useful for analyses of the small de novo inserted chromosomal segment.

Characteristics and outcome of intractable vasculitis syndrome in children: Nation-wide survey in Japan

Abstract Objective: Primary systemic vasculitis (PSV) is a rare disorder in children and difficult to distinguish from other diseases. However, appropriate diagnosis and prompt treatment will affect on the morbidity and mortality of intractable PSV. In this study, we conducted a nationwide survey in Japan, to clarify epidemiology and clinical outcome of PSV. Methods: We had sent survey questionnaires to most of the Japanese institutions that employed pediatricians, requesting the number of patients with refractory PSV who were diagnosed and treated between 2007 and 2011. Respondents were asked to provide detailed information on the clinical and laboratory features of each case they had managed. Those with Kawasaki disease or Henoch–Shönlein purpura vasculitis (IgA vasculitis) were excluded. Results: Of all the institutions surveyed, 1123 (37.3%) patients responded, finally, total of 49 patients with intractable PSV, defined by those with resistant to treatment and steroid-dependent, or with any complication associated with prognosis, were selected. The diagnosis was Takayasu arteritis in 31, polyarteritis nodosa in 11, granulomatosis with polyangitis in 2, microscopic polyangitis in 1, and ANCA negative microscopic polyangitis in 1. In those with Takayasu arteritis, 67% were treated with an immunosuppressive agent, 22% with biological modifiers, and 16% with surgical procedures. In other types of disease, 88% of the patients were treated with an immunosuppressive agent, and 12% with biological modifiers. Two with Takayasu arteritis died being terminally ill. Conclusion: This nationwide survey establishes the heterogeneous characteristics of PSV in children. Although questionnaire-based, the results of our analysis should be useful in planning prospective studies to identify the most effective therapy for each subtype of multifaceted disease.

Role of plasma exchange, leukocytapheresis, and plasma diafiltration in management of refractory macrophage activation syndrome

Macrophage activation syndrome (MAS) is a life‐threating complication of systemic juvenile idiopathic arthritis (s‐JIA). Steroid and cyclosporine (CsA) are effective for MAS, but, treatment for steroid‐ and CsA‐resistant patients is still challenging. We report the case of steroid and CsA resistant s‐JIA associated MAS misdiagnosed as Kawasaki disease (KD), who was successfully treated with the combination of plasma exchange (PE) and leukocytapheresis (LCAP) followed by plasma diafiltration (PDF). PE + LCAP effectively removed proinflammatory cytokines and reduced the number of peripheral white blood cells. Furthermore, PDF also removed proinflammatory cytokines as effectively as PE + LCAP. Early diagnosis of s‐JIA is necessary to avoid developing MAS. The measurement of serum ferritin and IL‐18 levels are useful for differentiating s‐JIA from KD. Apheresis therapies are an alternative option to induce remission for severe patients with steroid‐ or CsA‐resistant MAS.

Validation of Classification Criteria of Macrophage Activation Syndrome in Japanese Patients With Systemic Juvenile Idiopathic Arthritis

To validate whether the 2016 American College of Rheumatology/European League Against Rheumatism classification criteria of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (JIA) is practical in the real world.

Pediatric case of oral mucous pemphigus complicated by protein-losing gastroenteropathy

1 McGrath JA, Schofield OM, Eady RA. Epidermolysis bullosa pruriginosa: dystrophic epidermolysis bullosa with distinctive clinicopathological features. Br J Dermatol 1994; 130: 617–625. 2 Ozanic Bulic S, Fassihi H, Mellerio JE, McGrath JA, Atherton DJ. Thalidomide in the management of epidermolysis bullosa pruriginosa. Br J Dermatol 2005; 152: 1332–1334. 3 Banky JP, Sheridan AT, Storer EL, Marshman G. Successful treatment of epidermolysis bullosa pruriginosa with topical tacrolimus. Arch Dermatol 2004; 140: 794–796. 4 Yamasaki H, Tada J, Yoshioka T, Arata J. Epidermolysis bullosa pruriginosa (McGrath) successfully controlled by oral cyclosporin. Br J Dermatol 1997; 137: 308–310. 5 Tarutani M, Shiga T, Nakajima K, Nakano H, Sawamura D, Sano S. Dystrophic epidermolysis bullosa pruriginosa in a mother and daughter successfully treated by low dose cyclosporine. Eur J Dermatol 2013; 23: 727–729.