Antinuclear antibody studies in juvenile chronic arthritis.

This study of children with chronic arthritis confirms that patients at greatest risk for chronic iridocyclitis have a young age of onset and positive antinuclear antibodies (ANA). Children who are ANA negative have a low risk of iridocyclitis. When it occurs it is at a significantly older age. No child developing juvenile chronic arthritis over 9, even with positive ANA, had chronic iritis. There was remarkable variation in ANA titres; these correlated with erythrocyte sedimentation rate, active arthritis, and iridocyclitis. Maximum ANA titres were often seen very early in the disease but at this time were usually not associated with a poor prognosis. Histocompatibility antigens A2 and DRw8 were significantly increased, suggesting primary associations in pauciarticular arthritis with ANA. HLA-DR5 was associated with mild forms of arthritis and with absence of, or only mild, iritis. HLA-B15/w62 was associated with severe forms of eye involvement.     

Reiter's syndrome in an adolescent girl

This report describes a 14-year-old girl who presented with an Escherichia coli urinary tract infection followed by diarrhoea, arthritis and iritis. She had continuing symptoms intermittently for six months, but was HLA-B27 antigen negative. The occurrence of Reiter's syndrome is unusual in young females and we are not aware of any reports of reactive arthritis following E. coli urinary tract infection in children.     

Dermatological signs in Wilson's disease

Background:  Because no data on skin and mucosal findings of patients with Wilson's disease have been published so far, the aim of the present study was to investigate the prevalence of mucosal and skin findings in childhood Wilson's disease and to determine its specific dermatological findings, if any exist.
Methods:  Thirty-seven 4–17-year-old children with Wilson's disease were included. A complete skin, scalp skin, mucous membrane and nail examination was performed.
Results:  Of the children, 26 (70.3%) had at least one dermatological finding. Twenty-five (67.6%), five (13.5%), nine (24.3%) had at least one skin, mucosal and nail finding, respectively. The most prevalent dermatological diagnosis of the Wilson's disease patients was xerosis (45.7%). The presence of dermatological findings was not related to drug usage, severity of the disease, or malnutrition. The duration of the disease was not different in patients with or without dermatological findings. The frequency of skin findings alone, however, was high in relatively newly diagnosed patients (<2 years).
Conclusion:  Dermatologist should be aware of the various dermatological manifestations of Wilson's disease, because a careful and objective skin, mucosa, nail and hair examination may be indicative of a diagnosis of Wilson's disease, particularly in early cases.     

Autosomal dominant granulomatous arthritis, uveitis, skin rash, and synovial cysts

In 1985, Blau reported a family with 11 members in four generations affected by granulomatous arthritis, iritis, skin rash, and periarticular synovial cysts. We report a second family with these abnormalities, thereby confirming this syndrome as a distinct familial entity with transmission compatible with autosomal dominant inheritance. Affected members in our family included a mother and two daughters. Disease onset was at 10 months to 8 years of age. Each had uveitis, symmetric polyarthritis, and synovial cysts overlying the ankle and wrist joints. In addition, both daughters had an intermittent generalized erythematous papular rash that on biopsy revealed noncaseating granulomatous infiltration. All three patients improved during alternate-day steroid therapy. Recognition of this disorder as distinct from other, more common causes of arthritis is important because of the apparent autosomal dominant transmission and because of the excellent responses to low-dose steroid therapy.     

Phlebothrombosis revealing Beh?et's disease in a 13-year-old adolescent]

BACKGROUND. Beh?et's disease is rare in children and is exceptionally revealed by thrombophlebitis at this age of life. CASE REPORT. A girl, aged 13 years, was admitted after having suffered from thrombophlebitis of the right leg for 6 weeks. Her medical history included frequent attacks of aphthous stomatitis and conjunctivitis and one episode of iritis. At admission, thrombophlebitis with venous thrombosis was confirmed by Doppler; it was associated with aphthous gingivitis and two similar erosive lesions in the genital area. Technetium 99 perfusion scintiphotography revealed a right pulmonary embolism. The erythrocyte sedimentation rate was elevated but there was no change in coagulation factors or immunologic abnormalities, except for the presence of immune complexes and increased complement C3 component. Biopsy of the skin lesions showed vascularitis. There was no involvement of the eyes. The condition progressively improved with anticoagulant treatment for 1 year, followed by low doses of acetylsalicylic acid. CONCLUSION. Phlebothrombosis, a classic complication of Beh?et's disease in adults, revealed the disease in this girl. Its mechanism remains unclear and duration of anticoagulant treatment is still debated.     

Association of Severe Microcephaly, Short Palpebral Fissures, Micrognathia, Growth Retardation and Early Death: A New Syndrome

Four siblings presenting a combination of severe microcephaly, short and laterally downward slanting palpebral fissures, hypertelorism, micrognathia, and growth retardation are reported. The proband had congenital heart disease complicating these characteristic symptoms. The parents were not consanguineous. The karyotypes of the proband and parents were normal. The faces of three brothers of the proband were very much like that of the proband, but tvjo of them had cleft palates. Although it was confirmed that one of the three brothers did not have congenital heart disease, its presence in the other two could not be ascertained. All three older brothers died within one month after birth.     

Low-dose methotrexate in the treatment of severe juvenile rheumatoid arthritis and sarcoid iritis.

OBJECTIVE: To assess the efficacy of low-dose oral methotrexate (MTX) therapy for children with severe iritis. METHODS: MTX in a weekly dose of 7.25 to 12.5 mg/m2 was administered orally to four patients (two with juvenile rheumatoid arthritis [JRA] and two with sarcoidosis) with severe iritis not adequately controlled by topical and systemic corticosteroid therapy. The treatment was initiated with half of the total dose and increased every 2 weeks until the final dose was reached. Iritis was graded from 0 to +4 according to the density of cells in the anterior chamber of the eye. RESULTS: There were three girls and one boy with a mean age of 10.5 years. Two patients were African American and two were Caucasian. The mean age at onset of iritis was 6 years. The mean duration of MTX therapy was 28.8 months. Significant improvement was noted in two of the four patients in ocular inflammation, demonstrated by reduction of cell density from +4 to +1. Two patients had a mild improvement of the iritis. However, corticosteroids were significantly reduced in all patients. One patient was completely off steroids within 30 months of MTX therapy. In the remaining three cases, the steroid dose was successfully tapered from 0.82 mg/kg/d to 0.15 mg/kg/d (mean doses) within a mean duration of 20 months. No side effects were observed with MTX therapy. CONCLUSION: Low-dose MTX therapy was effective and safe, and displayed steroid-sparing properties in four children with severe iritis.     

Berger disease: Henoch-Schönlein syndrome without the rash

Identical 7-year-old twin boys each had a proved adenovirus infection at the same time. A few days later one developed florid Henoch-Sch?nlein purpura, severe alimentary tract symptoms, and transient joint symptoms. He had an acute nephritic syndrome, which progressed to nephrotic syndrome and renal insufficiency. Biopsy showed severe proliferative glomerulonephritis with crescents and marked deposition of IgA, IgG, C3, and fibrin. The second twin had hematuria and abdominal pain but no rash. Biopsy showed mesangial proliferative glomerulonephritis with mesangial deposits of IgA and, to a lesser extent, IgG and C3. The appearance was characteristic of Berger disease, and the subsequent clinical course has been that of symptomless microscopic hematuria and recurrent macroscopic hematuria with normal renal function. Immunologic studies have not revealed why these identical twins responded differently to the same provocation. Perhaps Berger disease may be considered a variant of Henoch-Sch?nlein nephritis.     

Skin, joint, and pulmonary changes in type I diabetes mellitus

Three hundred seventy-five patients with diabetes mellitus were examined for the presence of sclerodermalike skin changes, limited joint mobility, and vital capacity changes. Nineteen percent of patients had vital capacities 2 SDs below the mean of predicted values. There was no significant relationship between decreased vital capacities and duration of diabetes, sclerodermalike skin changes, limited joint mobility, smoking history, proteinuria, or retinopathy. Cutaneous involvement consisting of thickening, tightening, and/or a waxy quality of the skin was noted in 190 patients (51%). The severity of skin involvement correlated positively with the patients' duration of diabetes, age, severity of joint contractures, and diabetic retinopathy. Thus, sclerodermalike skin changes appear to reflect generalized connective tissue alterations in diabetes and may indicate increased risk for diabetic microvascular complications.     

Pseudomonas infection, allergy, and cystic fibrosis

The clinical significance of the high prevalence of positive immediate skin tests in cystic fibrosis is unclear. Using analysis of variance, we have tested the hypothesis that patients with allergic cystic fibrosis have worse lung disease than non-allergic patients. Clinical data, skin prick tests, total or specific IgE antibody levels, chest radiographs, and pulmonary function tests were obtained in 104 cystic fibrosis patients. Patients with positive immediate skin reactions to at least one allergen were more likely to be persistently colonised by Pseudomonas aeruginosa than skin test negative patients. The skin test positive patients were also significantly older (mean difference 2.15 years). Analysis of variance showed that pseudomonas infection was the most significant factor contributing to lung damage and the effect of allergy was not significant. Similar longitudinal analysis of pulmonary function over 5 years and study of the hospital admission rate showed that the only statistically significant factor associated with deterioration was colonisation with P. aeruginosa.     

Pseudomonas infection,allergy, and cystic fibrosis.

The clinical significance of the high prevalence of positive immediate skin tests in cystic fibrosis is unclear. Using analysis of variance, we have tested the hypothesis that patients with allergic cystic fibrosis have worse lung disease than non-allergic patients. Clinical data, skin prick tests, total or specific IgE antibody levels, chest radiographs, and pulmonary function tests were obtained in 104 cystic fibrosis patients. Patients with positive immediate skin reactions to at least one allergen were more likely to be persistently colonised by Pseudomonas aeruginosa than skin test negative patients. The skin test positive patients were also significantly older (mean difference 2.15 years). Analysis of variance showed that pseudomonas infection was the most significant factor contributing to lung damage and the effect of allergy was not significant. Similar longitudinal analysis of pulmonary function over 5 years and study of the hospital admission rate showed that the only statistically significant factor associated with deterioration was colonisation with P. aeruginosa.     

Pyoderma gangrenosum, a nonintestinal manifestation of Lesniowski-Crohn's disease in a 15 years old girl

In the clinical course of Lesniowski-Crohn's disease in children, gastrointestinal symptoms are predominant. Extraintestinal manifestations are found rarely, contrary to adults. Pyoderma gangrenosum is hardly ever observed but frequently coexists with colon involvement. The aim of the study was a presentation of 15 years old girl with Lesniowski-Crohn's disease and predominant joint and skin symptoms in form of pyoderma gangrenosum. Skin lesions were shaped in solitary ulcerations with cyanotic undermined border localized on legs and buttocks. After steroid therapy these changes were healed with permanent blue scar. Gastrointestinal symptoms though slight were characteristic. The girl had stools with some fresh blood and perianal lesions.     

Rheumatism and acne conglobata . Apropos of a new case, in a 13-year-old boy

With reference to a new case of acne conglobata-associated rheumatic disease in a thirteen-year-old boy, we recall the characteristics of the main joint and/or bone manifestations that may occur during severe flares of acne conglobata, but also acne fulminans or pustulosis of the palms and soles. Joint manifestations mainly involve the large proximal joints of the limbs and consist in pain rather than in signs of inflammation. Although recurrences may develop, joint disease responds to treatment of the acne combined with a non-steroidal antiinflammatory drug. Bone involvement consists in true rheumatic osteitis with hyperostosis responsible for densification and thickening of bone, mainly in the anterior chest wall and spine. The pathogenesis and nosologic place of these bone and joint manifestations remain controversial: they do not seem to represent true reactive arthritis and, although the B27 antigen is usually lacking, they have been likened to the group of spondylarthropathies, especially in those cases with sacroiliac involvement and enthesopathy . Oddly enough, they are reminiscent of some of the side effects of etretinate, an agent prescribed in these severe forms of acne. After a national survey carried out in 1986, the acronym SAPHO (Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis) was suggested to designate the range of skin, bone and joint manifestations observed.     

24 cases of human parvovirus B19 infection in children]

From January 1, 1987 through December 31, 1990, twenty-four pediatric patients with human parvovirus B19 (HPV B19) infection were seen. In every case the diagnosis was established by a positive capture immunoassay for IgM antibodies against the HPV B19. Four patients had hematologic manifestations, including one case of transient bone marrow aplasia revealing hereditary spherocytosis, one case of autoimmune hemolytic anemia with beta-thalassemia, and two cases of peripheral thrombocytopenia. Eight patients had skin lesions, with a morbilliform rash in six cases, erythema nodosum in one case, and Gianotti-Crosti syndrome in one case. No patients had erythema infectiosum. Seven patients developed joint manifestations: Henoch-Sch?nlein purpura in two cases, arthralgia in four cases, and polyarticular disease progressing to severe rheumatoid arthritis in a thirteen-year-old girl. Unremarkable symptoms of viral disease were seen in three patients. A five-month-old infant developed severe acute myocarditis. One patient with hepatitis A had acute liver failure. This study confirms the broad spectrum of clinical manifestations of HPV B19 infection. There were a number of unusual findings, including the high rate of joint manifestations (29%) and the severe course of some hematologic and myocardial manifestations. These results raise the question of whether the HPV B19 may be involved in the genesis of chronic juvenile arthritis.     

Biotin deficiency complicating parenteral alimentation: diagnosis, metabolic repercussions, and treatment

Biotin deficiency associated with total parenteral nutrition is an emerging clinical problem; criteria for diagnosis and dosage for treatment are unclear. We have diagnosed and successfully treated biotin deficiency in three patients. Each patient had alopecia totalis, hypotonia, and developmental delay. Two developed the characteristic scaly periorificial dermatitis; one had only an intermittent scaly rash on the cheeks and occipital scalp. Zinc and essential fatty acid supplements were adequate; serum zinc levels and triene/tetraene ratios confirmed sufficiency of these nutrients. None of the patients received biotin prior to diagnosis, and each had decreased excretion of urinary biotin and increased urinary excretion of organic acids diagnostic of deficiency of two biotin-dependent enzymes (methylcrotonyl-coenzyme A carboxylase and priopionyl-coenzyme A carboxylase). Only one patient had a plasma biotin concentration below the normal range (Ochromonicas danica assay). The rash, alopecia, and neurologic findings responded dramatically to biotin therapy (100 micrograms/day in all patients; an initial larger dose of 1 mg/day for 1 week plus 10 mg/day for 7 weeks in one patient), and did not recur. However, abnormal organic acid excretion persisted in one patient who did not receive the larger dose. We conclude that plasma biotin concentration does not reflect biotin status in all cases and speculate that the biotin supplement currently recommended for pediatric patients (20 micrograms/day) may not be adequate therapy for biotin deficiency and might not even be adequate to maintain normal biotin status during TPN.     

Childhood brucellosis--a microbiological, epidemiological and clinical study

A total of 5726 blood specimens (from children aged 14 years and younger) were studied for the serological evidence of brucellosis. Ninety-three (1.6 per cent) showed diagnostic agglutinin titres with a geometric mean titre of 403 (SD +/- 547). Forty-three (59.7 per cent) blood specimens yielded the growth of Brucella melitensis. Thirty-nine patients (41.93 per cent) were shepherds, who constituted the major occupational group affected in the present series. More than 60 per cent of the patients had a history of both consumption of fresh goat's milk and close animal contact. The habit of consuming fresh goat's milk to obtain relief from chronic ailments was noted in nine patients. Seventy-three (78.49 per cent) were males and 20 (21.51 per cent) were females, with a male to female ratio of 3:1. The disease occurred mainly in the school age group (mean age 10.3 years). All the patients had an acute history of less than 2 months. Forty-nine (52.68 per cent) patients presented with persistent fever, 19 (20.43 per cent) with joint pain, and the rest with a combination of fever and joint pain with and without low backache, fever being the commonest complaint. One case presented with involuntary movements of limbs alone and the other with burning feet only. Pityriasis alba was the consistent physical finding, with fever in the majority of the patients. The major joint found to be involved was the knee (52.77 per cent). The synovial fluid obtained from the knee joint of five patients demonstrated Brucella agglutinins and also three grew B. melitensis. Eight patients presented with complications that included skin lesions (3), carditis (2), neurobrucellosis such as chorea (1), peripheral neuritis (1), and meningitis (1). Brucella melitensis biotype 1 was successfully isolated from the papular eruption of one out of three cases who presented with skin lesions. To our knowledge this is the fourth confirmed isolation of B. melitensis from skin lesions with brucellosis, reported in the literature. The cerebrospinal fluid obtained from the meningitis patient was positive for B. agglutinins. To our knowledge chorea of brucellar origin appears to be the first case reported in the literature. In 15 cases (16.13 per cent) brucellosis was suspected clinically whereas 78 (83.87 per cent) cases, only serological evidence of brucellosis confirmed the diagnosis. None of the cases relapsed. In our experience an initial combination therapy with a three-drug regimen followed by a two-drug regimen for a minimum of 6 weeks has been found to be effective in the prevention of a relapse.     

Methylmalonic aciduria: a variant form of methylmalonyl coenzyme A apomutase deficiency.

Sisters aged 3 and 4 1/2 years, respectively, who had grown and developed normally were found to have methylmalonic aciduria. The elder had had only one previous illness, at 18 months, and was thriving at six years without treatment; she was excreting up to 2 gm methylmalonic acid per day. The younger sister died during her third episode of illness, at 3 years of age. Studies of cultured skin fibroblasts showed deficient methylmalonyl coenzyme A mutase apoenzyme activity; cobalamin metabolism was normal. There was a moderate response in cultured cells to large amounts of added hydroxycobalamin; but treatment of the patient with high doses of intramuscular vitamin B12 for ten days failed to lower the urinary excretion of methylmalonic acid.     

Klinefelter's syndrome (47,XXY) among men with systemic lupus erythematosus

Aim: To determine the rate of Klinefelter’s syndrome among men with systemic lupus erythematosus (SLE), and to determine whether the manifestations of SLE in these men are different from that seen in 46,XY men. Methods: A total of 276 men with SLE underwent a real‐time PCR procedure to screen for more than one X chromosome. Those with results consistent with two X chromosomes were further characterized by karyotype and FISH. Clinical manifestations of SLE were determined by interview, questionnaire and medical chart review. Each man with Klinefelter’s and SLE was matched to four 46,XY men with SLE. Rates of SLE manifestations were compared with chi‐square analyses. Results: We found seven of the 286 men with SLE had Klinefelter’s syndrome. Four of these seven were nonmosaic 47,XXY, while two were mosaic 46,XY/47,XXY and one was 46,XX/47,XXY. The men with 47,XXY did not have severe manifestations of SLE including no proliferative renal disease, neurological disease, thrombocytopenia, autoimmune haemolytic anaemia, discoid skin disease or anti‐RNP/Sm. Conclusion: 47,XXY is found in excess among men with SLE. Men commonly have SLE that is more severe than that found among women, but the 47,XXY men had less severe SLE than other men.     

Infantile systemic hyalinosis: report of four cases of a disease, fatal in infancy, apparently different from juvenile systemic hyalinosis

Four female Mexican-American infants, two siblings, had widespread deposit of hyaline material in skin, gastrointestinal tract, adrenals, urinary bladder, ovaries, skeletal muscles, thymus, parathyroids, and other loci. Clinical features included thickness and focal nodularity of skin, relatively short limbs and neck, gum hypertrophy, hypotonia and reduced movement, joint contractures, osteoporosis, growth failure, diarrhea, and recurrent infections. Clinical onset was in the first week, and all 4 patients died by age 20 months. Infantile systemic hyalinosis appears to be a specific, presumably autosomal recessive, genetic disease, differing from the disorder called systemic hyalinosis, juvenile hyaline fibromatosis, or Puretic syndrome. The biochemical defect and the pathogenetic mechanisms responsible for the pathologic and clinical features of this condition remain to be established.     

Popliteal cysts in children: prevalence, appearance and associated findings at MR imaging

Objective. The purpose of this study was to determine the prevalence of Baker's cysts on MR images in a paediatric orthopaedic population, to investigate the association of Baker's cyst with joint fluid and joint disorders in children, and to compare the MR appearance of Baker's cysts in children with that previously reported in adults. Materials and methods. Reports from 393 MR studies of the knee performed in children aged from 1 to 17 years were retrospectively reviewed for the presence of a Baker's cyst, joint effusion, meniscal tear, anterior cruciate ligament tear, or any other joint disorder. Results. A Baker's cyst was identified in 6.3 % (25/393) of patients. The MR images and clinical charts of patients with a Baker's cyst were reviewed. None of the 25 patients with a Baker's cyst had an associated anterior cruciate ligament tear or meniscal tear. Two patients had osteochondritis dissecans and two others had synovial disease (infection and juvenile rheumatoid arthritis). Joint fluid was demonstrated in 16 % (4/25) of patients with a Baker's cyst. There was no statistically significant association between presence of a Baker's cyst and presence of joint fluid. Conclusions. Baker's cyst is less prevalent in a paediatric orthopaedic population than in an adult population. In children, it seems that Baker's cyst is seldom associated with joint fluid, meniscal tear, or anterior cruciate ligament tear. On MR images, a communication between the Baker's cyst and the joint was not demonstrated in any of the patients. In addition, the presence of debris and cyst leakage was not observed. Received: 20 August 1998 Accepted: 15 February 1999