Connective Tissue Disease In Childhood Research Articles

A CASE REPORT OF CONNECTIVE TISSUE DISORDER- AN AYURVEDIC APPROACH

Connective tissue disease (CTDs), though rare in kids, is an important cause of morbidity. By general physician mostly misunderstood by rheumatoid arthritis. most of them involve multiple organ systems and are associated with presence of auto antibodies. Systemic lupus erythematosus (SLE) is the most common CTD, the others being Juvenile dermatomyositis, systemic sclerosis, mixed connective disease and Sjogren syndrome. The clinical presentation of CTD in childhood can range from an acute severe illness mimicking a serious infection, to an insidious onset of disease with gradual accumulation of symptoms and signs over weeks to months. The presence of multi-system involvement, evidence of inflammation and lack of any obvious cause should alert a clinician to the possibility of CTD. Diagnosis is usually clinical and features like malar rash, Raynaud’s phenomenon, photosensitivity, oral ulcers suggest a possibility of CTD. Presence of autoantibodies like anti-nuclear antibodies etc. provide supportive evidence to a diagnosis of CTD. Most CTDs are treated with immunosuppressive drugs with good success. The rationale for using Ayurvedic medicines is to restore normal life style and reverse the condition with lesser side effects. Patient of 11 years old was treated with an Ayurvedic formulations to replace the modern drugs. The patient got significant result with the help of Ayurvedic medicines.

Connective tissue diseases

Inflammatory mediators in connective tissue disorders. Systemic lupus erythematosus. Systemic sclerosis. Polymyositis and dermatomyositis. Sjogren's syndrome. Raynaud's phenomenon. Mixed connective tissue disease. Idiopathic vasculitis. Secondary vasculitis. Polmyalgia rheumatica and giant cell arteritis. Molecular biology of inherited disorders of connective tissue. Connective tissue disease in childhood. Systemic disorders with rheumatic manifestations. Rheumatoid arthritis. Therapeutics of the future.

Systemic Scleroderma in Childhood: A Case Report

©2014 Turkish League Against Rheumatism. All rights reserved. Juvenile systemic scleroderma is a rare chronic multi-system connective tissue disease in childhood. Although rare in children, it is an important cause of morbidity and mortality. Juvenile systemic scleroderma is one of the most severe rheumatologic conditions diagnosed in children. In this article, we report a six-year-old boy diagnosed with scleroderma.

Approach to a Patient with Connective Tissue Disease

Connective tissue disease (CTDs), though rare in childhood, are an important cause of morbidity. Most of them involve multiple organ systems and are associated with presence of autoantibodies. Systemic lupus eryethematosus (SLE) is the most common CTD, the others being Juvenile dermatomyositis, systemic sclerosis, mixed connective disease and Sjogren syndrome. The clinical presentation of CTD in childhood can range from an acute severe illness mimicking a serious infection, to an insidious onset of disease with gradual accumulation of symptoms and signs over wks to months. The presence of multi-system involvement, evidence of inflammation and lack of any obvious cause should alert a clinician to the possibility of CTD. Diagnosis is usually clinical and features like malar rash, Raynaud's phenomenon, Gottron's rash, photosensitivity, oral ulcers suggest a possibility of CTD. Presence of autoantibodies like anti-nuclear antibodies, anti-dsDNA etc. provide supportive evidence to a diagnosis of CTD. Most CTDs are treated with immunosuppressive drugs with good success. Early recognition and prompt treatment results in excellent outcome.

Characteristics of Patients with Juvenile Onset Systemic Sclerosis in an Adult Single-center Cohort

Systemic sclerosis (SSc) is a rare connective tissue disease in childhood. We compared the characteristics of adult patients with juvenile-onset SSc (jSSc) from a single-center cohort to an adult-onset group. Patients with disease onset before the age of 17 years were included in the jSSc cohort, while subjects with SSc onset after age 17 formed the adult-onset cohort. We identified 52 adult subjects with jSSc and compared them to 954 patients with adult-onset SSc. The mean ± SD age at disease onset of the patients with jSSc was 14 ± 2 years, 39 (75%) of them were women, and 24 (46%) had the diffuse cutaneous subset of SSc (dcSSc). There were no differences between the 2 cohorts in terms of sex and disease subset. Overlaps were significantly more frequent among the jSSc cohort (37%) compared to the adult-onset group (18%; p = 0.002). Autoantibody analysis demonstrated significantly more antitopoisomerase I antibody-positive subjects (33% vs 20%; p = 0.034) and significantly fewer anticentromere antibody-positive subjects (2% vs 25%; p < 0.001) in the jSSc cohort. Compared to the adult-onset group at 10 years from disease onset, survival was significantly higher among the subjects with jSSc (98% vs 75%; p = 0.001), pulmonary arterial hypertension had a significantly lower incidence (2% vs 14%; p = 0.032), and there was no difference in terms of pulmonary fibrosis (22% vs 21%) and cardiac scleroderma (3% vs 2%) between the 2 groups. The high survival rates and lower proportion of dcSSc in the adult jSSc cohort may represent a survival bias.

A Case Report of Successful Treatment With Immunoadsorption Onto Protein A in Mixed Connective Tissue Disease in Childhood

An 11-year-old male patient suffering mixed connective tissue disease with life-threatening pulmonary arterial hypertension, progressive heart failure (New York Heart Association class III-IV), skin ulcers, Raynaud's phenomenon and arthritis, showing no improvement after intensive immunosuppressive therapy or high dose steroids, was treated with immunoadsorption onto protein A. With a combined therapy of low-dose cortisone and bosentan and 22 sessions of immunoadsorption, his condition improved significantly and he continues in clinical remission. At the time of writing no further immunosuppressive therapy or immunoadsorption had been necessary. The patient is now 15 years old and healthy with an age-based constitution comparable to the normal population.

Overview of the clinical presentation of connective tissue diseases in children

The connective tissue diseases which may present in childhood with musculo skeletal symptoms such as joint and muscle pains and stiffness can be broadly divided into six groups: 1. Musculoskeletal symptoms as the typical presentation. Juvenile chronic/idiopathic arthritis (JCA/JIA) including systemic disease, Still’s disease [1], which may present only as a ‘puo’-pyrexia of unknown origin. 2. Relatively frequent presentation with musculoskeletal pain. Systemic lupus erythematosus (SLE) [2–5]. Dermatomyositis (JDMS) and polymyositis [4,5]. 3. Connective tissue disorders which may more rarely present with joint pain. Systemic sclerosis (Scleroderma) [2,3]. Polyarteritis nodosa [3]. 4. Acute childhood diseases which may present with musculoskeletal symptoms. Henoch Schonlein purpura (HSP) [3] – commonly and Kawasaki disease (KD) [3,5]. 5. Miscellaneous, including Sjogren’s syndrome, overlap syndromes [2,3,6] including mixed connective disease (MCTD) and Calcinosis Raynaud’s Ectopic Calcification Sclerodactyly and Telangiectasia (CREST). Other very rare vasculitic conditions including Wegener’s granulomatosis and Churg Strauss syndrome [3]. 6. Other rare conditions such as Sarcoid [2,3], Behcets disease [1], and Familial Mediterranean Fever may present with symptoms related to the musculoskeletal system, as may some malignancies of childhood. The clinical presentation of connective tissue disease in childhood can range from an acute severe illness mimicking a serious infection, to an insidious onset of disease that may only lead to recognition many months after the onset of symptoms. Many of the early symptoms can be non-specific and include malaise, fatigue, muscle aches and weakness, skin rash, arthropathy, abdominal pain, and fever. More specific symptoms may suggest a particular type of connective tissue disease [7]. Many of the diseases share as their common pathology vasculitis, i.e. inflammation of the blood vessels themselves [3]. The target blood vessels can be large vessels (Takayasu’s arteritis), medium (KD and Polyarteritis nodosa) and sometimes small vessels (Wegener’s granulomatosis, Churg Strauss syndrome and HSP) and this process can be responsible for many of the symptoms and the effects upon individuals and individual systems of the body. Vasculitis is a feature of the two commonest vasculitis illnesses seen in childhood HSP and KD, however given their frequency and common clinical presentation these two conditions are seen more in general paediatrics than in paediatric rheumatology. These connective tissue diseases can be compared to syphilis in earlier times, in so far as they are great mimickers of disease in specific systems and not only can they present with symptoms in many different organ systems, but during the course of the disease other organ systems can become involved. Hence while presenting symptoms may relate to inflammation of the musculo skeletal system (muscles and joints) and the skin, in addition to the upper and lower respiratory tract, the pleura/pericardium and peritoneum (serositis), the kidneys, the gastro-intestinal tract (git) and the haematological system may all also be involved in the disease process. Many of the disease are similar to their counterparts in adult medicine and in some the childhood presentation is emphasised in the term used in adult medicine for example Adult Onset Still’s disease (AOSD) to describe the rare form of systemic disease/ * Tel.: +44-151-2284811; fax: +44-151-2280328.

Mixed connective tissue disease in childhood: a nationwide retrospective study in Japan.

Sixty-six children with mixed connective tissue disease (MCTD) were analyzed by a nationwide prospective study. The diagnostic significance of Raynaud's phenomenon and positive anti-RNP antibody was confirmed, and additional symptoms including swelling of fingers, facial erythema, and polyarthralgia, and laboratory findings such as positive rheumatoid factor, hypergammaglobulinemia, and increased levels of myogenic enzymes, were variably positive. These clinical and laboratory characteristics of MCTD were critically different from those of systemic lupus erythematosus, indicating that MCTD is an independent entity of disease.

Mixed connective tissue disease in childhood

Since 1981, 21 children diagnosed with mixed connective tissue disease (MCTD) have been reported in detail in the literature in Japan. Overlapping clinical features and laboratory findings of these children were analyzed according to the established criteria of the Ministry of Health and Welfare, Japan. Mixed connective tissue disease in childhood typically begins with Raynaud's phenomenon preceded by several months or years with the appearance of other symptoms and signs including fever, arthralgia, myalgia, and/or progressive systemic sclerosis like skin manifestations. Serologically all the children with MCTD were positive for anti-ribonuclear protein (RNP) antibody with speckled-type antinuclear antibody. Hypergammaglobulinemia, positive rheumatoid factor, and normocomplementemia were characteristic. In general, prognosis is considered to be fairly good as opposed to systemic lupus erythematosus in childhood, but severe pericarditis/myocarditis or nephrotic syndrome can occur. Long-term follow-up study and improved laboratory detection of anti-ribonucleoprotein antibodies will be necessary for further characterization of MCTD in childhood, and for the improvement of therapy.

Mixed Connective Tissue Disease in Childhood

Rheumatic diseases with overlapping clinical features have been known since at least 1900 under such descriptive designations as "sclerodermatomyositis," "lupoderma," "rupus," and others. These hybrid descriptors recognize the occasional mixing of features of the classic rheumatic disorders, rheumatoid arthritis, scleroderma, dermatomyositis, and systemic lupus erythematous (SLE), in the same patient. However, because of the absence of precise pathogenetic and etiologic information, even the traditional rheumatic diseases have been largely classified on the basis of aggregations of clinical, histologic, and immunologic findings. In 1972, Sharp and colleagues first described 26 adults with a new syndrome, which they defined as mixed connective tissue disease (MCTD). A major contribution of Sharp and his colleagues was to name and attempt to classify an overlap syndrome in explicit clinical terms and to associate it with specific autoantibodies directed against "extractable nuclear antigen" (ENA). One year later, the first child with MCTD was reported, and in 1977 a series of 14 children with MCTD was first investigated. Where does mixed connective tissue disease, in both children and adults, stand now after more than a decade of study? Directly, the concept of MCTD has focused our attention upon the description of overlapping features of the rheumatic diseases, and it has forced us to confront whether "lumping" or "splitting" descriptors serves the patient from a therapeutic or prognostic point of view.

Mixed connective tissue disease in childhood.

Rheumatic diseases with overlapping clinical features have been known since at least 1900 under such descriptive designations as sclerodermatomyositis, lupoderma, rupus, and others. These hybrid descriptors recognize the occasional mixing of features of the classic rheumatic disorders, rheumatoid arthritis, scleroderma, dermatomyositis, and systemic lupus erythematous (SLE), in the same patient. However, because of the absence of precise pathogenetic and etiologic information, even the traditional rheumatic diseases have been largely classified on the basis of aggregations of clinical, histologic, and immunologic findings. In 1972, Sharp and colleagues first described 26 adults with a new syndrome, which they defined as mixed connective tissue disease (MCTD). A major contribution of Sharp and his colleagues was to name and attempt to classify an overlap syndrome in explicit clinical terms and to associate it with specific autoantibodies directed against extractable nuclear antigen (ENA). One year later, the first child with MCTD was reported, and in 1977 a series of 14 children with MCTD was first investigated. Where does mixed connective tissue disease, in both children and adults, stand now after more than a decade of study? Directly, the concept of MCTD has focused our attention upon the description of overlapping features of the rheumatic diseases, and it has forced us to confront whether lumping or splitting descriptors serves the patient from a therapeutic or prognostic point of view.

A histologic evaluation of mixed connective tissue disease in childhood

Mixed connective tissue disease (MCTD) includes features of scleroderma, dermatomyositis and systemic lupus erythematosus (SLE), and has speckled antinuclear antibodies (ANA) and high titers of anti-RNP antibodies. There are no comprehensive investigations of its histopathology. We have followed 15 children with MCTD, of whom four have died (mean disease duration prior to death 5.4 years). The immediate causes of death were pneumococcal sepsis (two patients), meningococcal sepsis (one patient) and uncontrollable thrombocytopenia (one patient). Material from the three available autopsies and five renal biopsies was reviewed. The most prominent histopathologic feature was widespread proliferative vascular lesions including intimai vascular change in 31 of 58 organs (53 per cent) and medial vessel wall thickening in nine organs (16 per cent). Systemic hypertension was absent; the normal vascular responses to aging could be excluded. Inflammatory infiltrates, often with prominent plasmacytosis, were present in 26 of 58 organs (45 per cent), but fibrinoid vascular change (9 per cent) and fibrosis (14 per cent) were rare. Eight renal specimens all showed some degree of glomerulonephritis; membranous change was present in three, and six showed significant vascular sclerosis. The histopathology of MCTD is superficially similar to systemic sclerosis, but it may be distinguished by less frequent fibrosis, the frequency of organs with intimal vascular change, and a predilection for intimai thickening of large arteries including coronary, pulmonary, renal and aortic. A distinctive replacement of muscle layers by hyaline in the gastrointestinal tract, and an unusual nodular hyperplasia of the thymic medulla were also observed and may be unique features of MCTD. The findings from this study suggest an immunologic basis for MCTD different from those postulated for other rheumatic diseases, and strongly suggest that adjustment of morbidity and mortality expectations for MCTD are necessary.

A histologic evaluation of mixed connective tissue disease in childhood: Singsen BH, Swanson VL, Bernstein BH, Heuser ET, Hanson V, Landing BH: Am J Med 1980; 68: 710–717

A histologic evaluation of mixed connective tissue disease in childhood: Singsen BH, Swanson VL, Bernstein BH, Heuser ET, Hanson V, Landing BH: Am J Med 1980; 68: 710–717

Mixed connective tissue disease in childhood: A clinical and serologic survey

Mixed connective tissue disease is a syndrome with overlapping clinical features of SLE, scleroderma, and polymyositis. Only one other child with MCTD has been described in detail. In this study 14 children with MCTD are described. Each had overlapping clinical findings that evolved over an extended period of observation, and all 14 had high serum titers of speckled ANA and antibodies to RNP. A serologic survey of 127 children with various rheumatic diseases confirmed the specificity of high titer of speckled ANA and antibodies to RNP for MCTD in children. Significant cardiac and renal involvement, and thrombocytopenia, may be more common in affected children than in adults with MCTD, may lead to longer therapy with higher doses of a corticosteroid, and may contribute to a more serious prognosis than in adults.