Juvenile idiopathic arthritis with peripheral gangrene
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《美国医学杂志》
1 Department of Pediatric Medicine, IPGMER & SSKM Hospital, Kolkata, India
2 Department of Obstet. & Gynae, IPGMER & SSKM Hospital, Kolkata, India
Abstract
Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disorder of the childhood and is manifested by synovitis with or without systemic features. Secondary vasculitis occurring in response to JIA is reflected clinically on different structures or systems of the body. Here is reported a rare case of systemic onset JIA (SOJIA) with vasculitis leading to peripheral gangrene.
Keywords: Juvenile rheumatoid arthritis; Vasculitis; Peripheral gangrene
Juvenile idiopathic arthritis (JIA), which consists of heterogenous clinical features, is the commonest rheumatologic disease in children. JIA is a broad term including a group of disorders characterized by chronic arthritis. It is a clinical diagnosis made in a child less than sixteen years of age with arthritis (defined as swelling or limitation of motion of the joint accompanied by heat, pain or tenderness) for at least six weeks duration with other identifiable causes of arthritis excluded. The International League of Associations for Rheumatology classification system of JIA includes seven subtypes: systemic onset JIA (SOJIA), oligoarticular, polyarticular Rheumatoid Factor positive and Rheumatoid Factor negative, Enthesitis related arthritis, Juvenile psoriatic arthritis and "other". Vasculitis refers to inflammation and necrosis of blood vessels.[1],[2] Indian literature on childhood vasculitis is limited.[3] Apart from primary vasculitides, vasculitis can occur secondary to connective tissue diseases like dermatomyositis (DM) ,systemic lupus erythematosus (SLE), juvenile idiopathic arthritis (JIA). Peripheral gangrene of the fingers and toes may ensue as a complication of rheumatoid arthritis necessitating amputation in adults.[4] Here is reported a case of SOJIA leading to gangrene of foot as a consequence of vasculitis because of its rarity in children.
Case Report
A 4-year-old male child born to nonconsanguinous parents presented with history of recurrent bouts of high fever associated with joint pain for seven months. He had also pain and blackish discoloration of right foot for last one month. Arthritis involved large joints namely knee, ankle, elbow and wrist bilaterally. Arthritis was additive in nature. There was no history of skin rash, jaundice, bleeding manifestation, respiratory difficulty and convulsion. Blackish discoloration started over pulp of the toes on right side and gradually progressed upwards to affect up to mid foot region. History suggestive of Raynaud's phenomenon was not available. On examination the child had mild anemia and blood pressure of 90/64 mm of Hg. All the peripheral pulses showed average volume with rate of 86/minute except right popliteal, dorsalis pedis and posterior tibial artery which were almost imperceptible. Abdominal examination showed firm, nontender liver 3.5 cm below right costal arch and firm spleen 2.5 cm below left costal arch. Right foot was found to be gangrenous from midfoot region to the tip of all toes. Figure1. Both the knee joints had evidence of arthritis. The rest of the clinical examination was noncontributory.
The complete hemogram revealed hemoglobin of 9.5 gm/dl, total leucocyte count 19,700/ cu.mm with neutrophils 55%, lymphocyte 40%, monocyte 2% and eosinophil 3%. The RBCs were normocytic, normochromic type. The erythrocyte sedimentation rate was 77 mm at the end of first hour. Reticulocyte count was 2 %. Platelet count was 95,000 /cu.mm. Blood urea and serum creatinine levels were normal. Skiagram of chest revealed no abnormality. X-ray of the right knee showed widened joint space. No abnormality was detected on routine analysis of urine. Fetal hemoglobin content of blood was 2 %. Hemoglobin electrophoresis showed no abnormality. The Rheumatoid Factor was 62.61 i.u/ml (Normal value: < 40 i.u./ml), C-reactive protein (CRP) level was 7.82 mg/dl (Normal: up to 0.6 mg/dl). The antinuclear antibody (ANA) and antidouble-stranded DNA antibody (anti ds-DNAantibody) titer was 0.22 and 18 iu/ml respectively (Normal value for ANA : < 1 i.u/ml; Normal value for anti ds DNA antibody: < 35 i.u/ml). Hepatitis B surface antigen test was negative. C-antineutrophil cytoplamic antibody (c-ANCA) and p-antineutrophil cytoplasmic antibody (p-ANCA) levels were 1.7 u/ml and 2.60 u/ml respectively (Normal values for both c-ANCA and p-ANCA : < 7 u/ml). Antiphospholipid antibodies (IgG & IgM) were negative. Transthoracic two-dimentional echocardiography with color Doppler revealed no abnormality. Transesophageal echocardiography with high resolution probe also showed no vegetation. Skin biopsy from gangrenous area showed that epidermis was ulcerated, base of which was having capillaries with fibrinoid necrosis. The dermis revealed perivascular infiltration of lymphocytes. Doppler ultrasonography of both lower limb arteries showed evidence of bilateral occlusive changes. Three sets (one set for arobic and another set for anerobic) of blood culture taken at different times in the first 24 hours of hospitalization did not reveal any organism. Abdominal angiogram to study medium sized arteries such as celiac and mesenteric axis for radiologic documentation of systemic vasculitis specially to exclude polyarteritis nodosa ( PAN) could not be done in view of economic constraint of parents.
Treatment was started with ibuprofen and prednisolone daily. After two weeks of therapy arthritis disappeared and CRP, platelet count were normalized. Gangrene, organomegaly did not show any change even after four weeks of treatment when ibuprofen was withdrawn. Potent immunosuppressive drugs methotrexate, cyclophosphamide, azathioprine etc were not considered for theraupeutic regimen in view of gradual progressive improvement of disease activity and no further appearance of newer ischaemic manifestations mediated by treatment with corticosteroid and ibuprofen. Amputation of right foot was done on sixth week of treatment. After ten weeks of treatment during follow up at outpatient department hepatosplenomegaly showed regression. ESR, CRP, platelet count remained normal.
Discussion
Secondary vasculitis most commonly occurs in SOJIA amongst other connective tissue diseases like SLE and DM. Extra-articular manifestation occasionally seen in polyarticular and pauciarticular onset type of JIA also can be explained by vasculitis. There is a wide spectrum of clinical features of systemic rheumatoid vasculitis reflecting the spectrum of vessel size involved.[5] Vasculitis leads to extra-articular manifestations like hepatosplenomegaly, cardiovascular affection viz pericarditis, myocarditis, endocarditis; rheumatoid nodule, pleurisy, neurological features like cervical myelopathy, mononeuritis multiplex etc; loss of body weight, cutaneous manifestations including a variety of skin rashes, nailfold infarcts, skin ulcers, peripheral gangrene etc. The peripheral gangrene, the most definitive cutaneous manifestatuion is relatively uncommon in adult rheumatoid arthritis.[5],[6] The digital gangrene affecting all the toes including foot unilaterally has rarely been observed in JIA. SLE was ruled out by the absence of raised ANA and anti-dsDNA antibody titre. PAN was excluded by the absence of raised ANCA, HbsAg, absence of typical beading of vessels on Doppler ultrasonography by alternating areas of vascular narrowing and dilatation. Because of pleomorphism, multisystemic manifestations both PAN and SLE may be confused with SOJIA. Infective endocarditis (IE) may have protean manifestations like pyrexia, musculoskeletal symptoms, splenomegaly ,anemia etc. Blood culture and echocardio-graphy excluded IE. Sickle cell anemia may present with hand foot syndrome, fever, anemia, arthralgia etc. It was also ruled out by normal fetal hemoglobin electrophoresis. Diagnosis of SOJIA was entertained in the present case after exclusion of these closely simulating diseases. The prevalence of anti-phospholipid antibody (APLA) has been found to be ranging from 7% to 53% in JIA.[7] In JIA with gangrene, negative APLA may not rule out the diagnosis. Skin biopsy confirmed the presence of necrotising vasculitis though it is not pathognomic of JIA only. Digital gangrene seen in PAN and SLE is usually bilaterally symmetrical. In JIA peripheral gangrene may be unilateral as evident from the index case . Doppler ultrasonography though revealed vascular narrowing of lower limb vessels on both sides, its clinical reflection to produce gangrene was seen unilaterally. To conclude, SOJIA should be considered as a possible cause of peripheral gangrene in suspected multisystemic connective tissue disorder specially when gangrene is asymmetrical.
References
1. Dillon MJ. Vasculitis. Curr Paediatr 1991; 1 : 89-92.
2. Rott KT, Gozalez EB, Conn DL. Cutaneous Small -Vessel Vasculitis In Harris ED Jr, Budd RC, Genovese MC, Firestein GC, Sargent JS, Sledge CB, eds. Kelly's Textbook of Rheumatology , 7th edn. Philadelphia ; Elsevier Saunders 2005; 1388-1395.
3. Kumar A, Malviya AN, Bhat A et al. Clinicopathological profile of vasculitides in India. J Assoc Phy India 1985; 33: 694-698.
4. Cummings JK, Taleisnik J. Peripheral gangrene as a complication of rheumatoid arthritis. Report of a case and a review of the literature. J Bone J Sur 1971; 53A: 1000-1002.
5. Bacon PA, Carruthers D.Vasculitis associated with connective tissues disorders. Rheum Dis Clin North Am 1995; 21(4): 1077-1096.
6. Jorizzo JL, Daniels JC. Dermatologic conditions reported in patients with R A. J Am Acad Derm 1983; 8 : 439-457.
7. Ravelli A, Martini A. Antiphospholipid antibody syndrome in pediatric patients. Rheum Dis Clin N Am 1997; 23(3) : 657-676.(Ghosh JB, Gupta Dipankar,)
2 Department of Obstet. & Gynae, IPGMER & SSKM Hospital, Kolkata, India
Abstract
Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disorder of the childhood and is manifested by synovitis with or without systemic features. Secondary vasculitis occurring in response to JIA is reflected clinically on different structures or systems of the body. Here is reported a rare case of systemic onset JIA (SOJIA) with vasculitis leading to peripheral gangrene.
Keywords: Juvenile rheumatoid arthritis; Vasculitis; Peripheral gangrene
Juvenile idiopathic arthritis (JIA), which consists of heterogenous clinical features, is the commonest rheumatologic disease in children. JIA is a broad term including a group of disorders characterized by chronic arthritis. It is a clinical diagnosis made in a child less than sixteen years of age with arthritis (defined as swelling or limitation of motion of the joint accompanied by heat, pain or tenderness) for at least six weeks duration with other identifiable causes of arthritis excluded. The International League of Associations for Rheumatology classification system of JIA includes seven subtypes: systemic onset JIA (SOJIA), oligoarticular, polyarticular Rheumatoid Factor positive and Rheumatoid Factor negative, Enthesitis related arthritis, Juvenile psoriatic arthritis and "other". Vasculitis refers to inflammation and necrosis of blood vessels.[1],[2] Indian literature on childhood vasculitis is limited.[3] Apart from primary vasculitides, vasculitis can occur secondary to connective tissue diseases like dermatomyositis (DM) ,systemic lupus erythematosus (SLE), juvenile idiopathic arthritis (JIA). Peripheral gangrene of the fingers and toes may ensue as a complication of rheumatoid arthritis necessitating amputation in adults.[4] Here is reported a case of SOJIA leading to gangrene of foot as a consequence of vasculitis because of its rarity in children.
Case Report
A 4-year-old male child born to nonconsanguinous parents presented with history of recurrent bouts of high fever associated with joint pain for seven months. He had also pain and blackish discoloration of right foot for last one month. Arthritis involved large joints namely knee, ankle, elbow and wrist bilaterally. Arthritis was additive in nature. There was no history of skin rash, jaundice, bleeding manifestation, respiratory difficulty and convulsion. Blackish discoloration started over pulp of the toes on right side and gradually progressed upwards to affect up to mid foot region. History suggestive of Raynaud's phenomenon was not available. On examination the child had mild anemia and blood pressure of 90/64 mm of Hg. All the peripheral pulses showed average volume with rate of 86/minute except right popliteal, dorsalis pedis and posterior tibial artery which were almost imperceptible. Abdominal examination showed firm, nontender liver 3.5 cm below right costal arch and firm spleen 2.5 cm below left costal arch. Right foot was found to be gangrenous from midfoot region to the tip of all toes. Figure1. Both the knee joints had evidence of arthritis. The rest of the clinical examination was noncontributory.
The complete hemogram revealed hemoglobin of 9.5 gm/dl, total leucocyte count 19,700/ cu.mm with neutrophils 55%, lymphocyte 40%, monocyte 2% and eosinophil 3%. The RBCs were normocytic, normochromic type. The erythrocyte sedimentation rate was 77 mm at the end of first hour. Reticulocyte count was 2 %. Platelet count was 95,000 /cu.mm. Blood urea and serum creatinine levels were normal. Skiagram of chest revealed no abnormality. X-ray of the right knee showed widened joint space. No abnormality was detected on routine analysis of urine. Fetal hemoglobin content of blood was 2 %. Hemoglobin electrophoresis showed no abnormality. The Rheumatoid Factor was 62.61 i.u/ml (Normal value: < 40 i.u./ml), C-reactive protein (CRP) level was 7.82 mg/dl (Normal: up to 0.6 mg/dl). The antinuclear antibody (ANA) and antidouble-stranded DNA antibody (anti ds-DNAantibody) titer was 0.22 and 18 iu/ml respectively (Normal value for ANA : < 1 i.u/ml; Normal value for anti ds DNA antibody: < 35 i.u/ml). Hepatitis B surface antigen test was negative. C-antineutrophil cytoplamic antibody (c-ANCA) and p-antineutrophil cytoplasmic antibody (p-ANCA) levels were 1.7 u/ml and 2.60 u/ml respectively (Normal values for both c-ANCA and p-ANCA : < 7 u/ml). Antiphospholipid antibodies (IgG & IgM) were negative. Transthoracic two-dimentional echocardiography with color Doppler revealed no abnormality. Transesophageal echocardiography with high resolution probe also showed no vegetation. Skin biopsy from gangrenous area showed that epidermis was ulcerated, base of which was having capillaries with fibrinoid necrosis. The dermis revealed perivascular infiltration of lymphocytes. Doppler ultrasonography of both lower limb arteries showed evidence of bilateral occlusive changes. Three sets (one set for arobic and another set for anerobic) of blood culture taken at different times in the first 24 hours of hospitalization did not reveal any organism. Abdominal angiogram to study medium sized arteries such as celiac and mesenteric axis for radiologic documentation of systemic vasculitis specially to exclude polyarteritis nodosa ( PAN) could not be done in view of economic constraint of parents.
Treatment was started with ibuprofen and prednisolone daily. After two weeks of therapy arthritis disappeared and CRP, platelet count were normalized. Gangrene, organomegaly did not show any change even after four weeks of treatment when ibuprofen was withdrawn. Potent immunosuppressive drugs methotrexate, cyclophosphamide, azathioprine etc were not considered for theraupeutic regimen in view of gradual progressive improvement of disease activity and no further appearance of newer ischaemic manifestations mediated by treatment with corticosteroid and ibuprofen. Amputation of right foot was done on sixth week of treatment. After ten weeks of treatment during follow up at outpatient department hepatosplenomegaly showed regression. ESR, CRP, platelet count remained normal.
Discussion
Secondary vasculitis most commonly occurs in SOJIA amongst other connective tissue diseases like SLE and DM. Extra-articular manifestation occasionally seen in polyarticular and pauciarticular onset type of JIA also can be explained by vasculitis. There is a wide spectrum of clinical features of systemic rheumatoid vasculitis reflecting the spectrum of vessel size involved.[5] Vasculitis leads to extra-articular manifestations like hepatosplenomegaly, cardiovascular affection viz pericarditis, myocarditis, endocarditis; rheumatoid nodule, pleurisy, neurological features like cervical myelopathy, mononeuritis multiplex etc; loss of body weight, cutaneous manifestations including a variety of skin rashes, nailfold infarcts, skin ulcers, peripheral gangrene etc. The peripheral gangrene, the most definitive cutaneous manifestatuion is relatively uncommon in adult rheumatoid arthritis.[5],[6] The digital gangrene affecting all the toes including foot unilaterally has rarely been observed in JIA. SLE was ruled out by the absence of raised ANA and anti-dsDNA antibody titre. PAN was excluded by the absence of raised ANCA, HbsAg, absence of typical beading of vessels on Doppler ultrasonography by alternating areas of vascular narrowing and dilatation. Because of pleomorphism, multisystemic manifestations both PAN and SLE may be confused with SOJIA. Infective endocarditis (IE) may have protean manifestations like pyrexia, musculoskeletal symptoms, splenomegaly ,anemia etc. Blood culture and echocardio-graphy excluded IE. Sickle cell anemia may present with hand foot syndrome, fever, anemia, arthralgia etc. It was also ruled out by normal fetal hemoglobin electrophoresis. Diagnosis of SOJIA was entertained in the present case after exclusion of these closely simulating diseases. The prevalence of anti-phospholipid antibody (APLA) has been found to be ranging from 7% to 53% in JIA.[7] In JIA with gangrene, negative APLA may not rule out the diagnosis. Skin biopsy confirmed the presence of necrotising vasculitis though it is not pathognomic of JIA only. Digital gangrene seen in PAN and SLE is usually bilaterally symmetrical. In JIA peripheral gangrene may be unilateral as evident from the index case . Doppler ultrasonography though revealed vascular narrowing of lower limb vessels on both sides, its clinical reflection to produce gangrene was seen unilaterally. To conclude, SOJIA should be considered as a possible cause of peripheral gangrene in suspected multisystemic connective tissue disorder specially when gangrene is asymmetrical.
References
1. Dillon MJ. Vasculitis. Curr Paediatr 1991; 1 : 89-92.
2. Rott KT, Gozalez EB, Conn DL. Cutaneous Small -Vessel Vasculitis In Harris ED Jr, Budd RC, Genovese MC, Firestein GC, Sargent JS, Sledge CB, eds. Kelly's Textbook of Rheumatology , 7th edn. Philadelphia ; Elsevier Saunders 2005; 1388-1395.
3. Kumar A, Malviya AN, Bhat A et al. Clinicopathological profile of vasculitides in India. J Assoc Phy India 1985; 33: 694-698.
4. Cummings JK, Taleisnik J. Peripheral gangrene as a complication of rheumatoid arthritis. Report of a case and a review of the literature. J Bone J Sur 1971; 53A: 1000-1002.
5. Bacon PA, Carruthers D.Vasculitis associated with connective tissues disorders. Rheum Dis Clin North Am 1995; 21(4): 1077-1096.
6. Jorizzo JL, Daniels JC. Dermatologic conditions reported in patients with R A. J Am Acad Derm 1983; 8 : 439-457.
7. Ravelli A, Martini A. Antiphospholipid antibody syndrome in pediatric patients. Rheum Dis Clin N Am 1997; 23(3) : 657-676.(Ghosh JB, Gupta Dipankar,)