LETTERS TO THE EDITOR
M. KLOCKARS,T. PETTERSSON,P. VILJA, R. VON ESSEN
Institute of Occupational Health, Helsinki; Fourth Department of Medicine, Helsinki University Hospital; Department of Anatomy, University of Tampere; Rheumatism Foundation Hospital, Heinola, Finland Received 4 April 1990 1. Thompson PW. Laboratory markers of joint inflammation and damage. Br J Rheumatol 1987 ;26:131-5. 2. Giusti G. Adenosine deaminase. In: Bergmayer HU, ed. Methodsofenzymaticanalysis. Vol. 2.2nded. New York, NY: Academic Press, 1974. 3. Vilja P, Krohn K,TuohimaaP. A rapid and sensitive non-competitive avidin-biotin assay for lactoferrin. J Immunol Methods 1985; 76:73-83. 4. Miles LEM, Lipschitz DA, Bieber CP, Cook JD. Measurement of serum ferritin by a 2-site immunoradiometnc assay. AnalBiochem 1974 ;61:209-24. 5. Blake DR, Bacon PA, Eastham EJ, Brigham K. Synovial fluid ferritin in rheumatoid arthritis. Br MedJ 1980;281:715-16. 6. Malmqvist J,Thorell Jl, Wollheim FA. Lactoferrin and lysozymein arthriticexudates. ActaMcdScand 1977;202:313-18. 7. Pettersson T, Klockars M, Weber TH, von Essen R. Adenosine deaminase activity in joint effusions. Scand J Rheumatoll980;W-.365-9. 8. Smiley DJ, Hoffman WL, Moore SE, Paradies LH. The humoral immune response of the rheumatoid synovium. Semin Arthritis Rheum 1985; 14:151-62. 9. Blake DR, Gallagher PJ, Potter AR, Bell MJ, Bacon PA. The effect of synovial iron on the progression of rheumatoid disease. Arthritis Rheum 1984;27:495-501.
10. Tritsch GL, Niswander PW. Adenosine deaminase activity and superoxide formation during phagocytosis and membrane perturbation of macrophages. Immunol Commun 9810l ll.Freemont AJ, Rutley C. Distribution of immunoglobulin heavy chains in diseased synovia. J Clin Pathol l9&6;39:13\-5. 12. Warren JS, Kunkel RG, Simon RH, Johnson KJ, Ward PA. Ultrastructural cytochemical analysis of oxygen radicalmediated immunoglobulin A immune complex induced lung injury in the rat. Lab Invest 1989;60:651-8. 13. KlockarsM,HedenborgM,KoistinenJ,IsobeT. IgG and IgA enhance the chrysotile induced production of reactive oxygen metabolites by human PMN. Clin Exp Immunol 1989;78:372-7.
Is this a Record? SIR—The patient whose pelvic X-ray is shown (Fig.) is a female age 72. She was diagnosed as having 'synovitis' of the knees aged 10. Despite this she continued with physical education at school and coped until the age of 16 when she had a severe attack of pain in the hips which precluded her sitting down and which was treated with 6 weeks of bed rest. The working diagnosis was rheumatoid arthritis and subsequent developments have supported this diagnosis. Aged 18 she was admitted to the Royal Bath Hospital in Harrogate on account of her hip pain and treated by Dr Yeoman with just one piece of advice that she remembers, namely 'never ride a horse'. Matters improved, in that she was able to go on a walking holiday to Switzerland age 21. During her in-patient stay she had received gold therapy (1935) and then had a further course as an in-patient towards the end of the war when she required a further inpatient admission for 6 months, being placed in a double abduction frame (Bradford Royal Infirmary). The Adams' prosthesis was inserted in 1953 by Mr James Wishart. (Prior to this the only prosthesis used was Petersen's and was not very satisfactory.) John CrawfordAdams devised the Adams' prosthesis, which on the outside was the diameter of the acetabulum but inside was much smaller and fitted the head of the femur. It was therefore considered particularly suitable for rheumatoid cases in which there had been considerable loss of bone from the femoral head. John Crawford-Adams fitted only about 40 of these and possibly 20 were satisfactory. The firm which made them was called Willens and is no longer in business. The right Charnley prosthesis was inserted in 1972 fol-
FIG.
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Michigan on June 28, 2015
All of the measured proteins, ferritin, lactoferrin, ADA and immunoglobulins, have been implicated as important contributors to the synovial inflammation [5-8]. ADA is a ubiquitous enzyme, with the greatest concentrations occurring in T-lymphocytes. Lactoferrin is released from neutrophilic granulocytes in acute infections and other inflammatory conditions, and cells of the mononuclear phagocyte system display the largest synthetic capacity of ferritin. In the rheumatoid joint, iron may promote inflammation by interaction with the cascade of reactive oxygen metabolites formed by polymorphonuclear leucocytes in the synovial fluid [9]. Even ADA has been suggested to interfere with oxygen free radical formation; macrophages generate superoxide radicals in direct proportion to their intracellular ADA activity [10]. A relatively high proportion of IgA-positive plasma cells in inflamed synovium has been observed, and it has been reported that these cells selectively enter the tissue under the specific local influence of T-helper cells [11]. Tissue injury induced by the IgA immune complex appears to be mediated by reactive oxygen metabolites [12]. For some phagocytic material, IgG and IgA enhance the formation of reactive oxygen metabolites by human polymorphonuclear leucocytes in vitro [13]. Local immunoglobulins may thus affect the potential tissue injury cascade of reactive oxygen metabolites produced by phagocytic cells within the joint. From the diagnostic point of view, our results are in agreement with reports stating that synovial fluid ferritin determination is not a suitable test for discriminating between rheumatic diseases of different aetiology. The observations that synovial fluid ADA concentrations are higher in patients with RA and reactive arthritis than in patients with O A and the demonstration that ADA activity in synovial fluid from patients with inflammatory arthritis correlates with general disease activity as measured by haemoglobin concentration and ESR may support the use of synovial fluid ADA determinations for the clinical follow-up of patients with inflammatory joint diseases.
319
3X)
BRITISH JOURNAL OF RHEUMATOLOGY VOL. XXIX NO. 4
lowing a fractured neck of femur by Mr Brian Hamilton when the patient was still under the care of Mr James Wishart. Current walking tolerance is 400 metres, limited more because of stiff knees. She does not require a walking aid. She feels that the left hip prosthesis has always functioned better than the later replacement on the right. WENDY DODDS
St Lukes Hospital, Bradford, W. Yorkshire BD5 ON A Received 5 April 1990 Infected Foreign Body due to Bacillus licheniformis in Rheumatoid Arthritis
L. A. T. DAVID, M. LYONS*, A. SAMANTA, M. PRENTICE*,
F. E. NICHOL
Departments of Rheumatology and * Microbiology, Leicester Royal Infirmary, Leicester LEI 5WW. Received 6 April 1990
I
I
i
FIG.—Thorn removed from the dorsum of the hand.
1. Kaye BR, Kaye RL, Bolsrove A. Rheumatoid nodules: review of a new classification, with a report of four seronegative cases. Am J Med 1984;76:279-92. 2. GardnerDL. In: Thepathologyofrheumatoid arthritis. Baltimore: Williams &Wilkins, 1972. 3. Davenport R, Smith C. Panophthalmitis due to an organism of the Bacillussubtilis group. Br J Ophthalmol 1952;36:389-92. 4. Raphael SS, Donaghue M. Infection due to Bacillus cereus. Can MedAssocJ 1976;115(3):207. 5. CurtisJR,WingAJ,ColemanJC. Bacilluscereus bacteraemia; a complication of intermittent haemodialysis. Lancet 1967;i:136. 6. Tuazon C, Murray H, Levy C, Solny M, Curtin J, Sheagren J. Serious infections from Bacillus species. JAMA 1979;241:1137-40.
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Michigan on June 28, 2015
SIR—Rheumatoid nodules or synovial or tendon swellings occur in at least 20% of patients with classical rheumatoid arthritis (RA). However, the differential diagnosis of subcutaneous nodules is wide, and even in established RA other causes should be excluded. We report a case in which infection of a subcutaneous foreign body with an unusual organism produced diagnostic confusion in a patient with RA. A 64-year-old farm worker initially presented with a 6-month history of early morning stiffness of wrists, symmetrical swelling of metacarpophalangeal, proximal interphalangeal, and metatarsophangeal joints. Plasma viscosity and C-reactive protein were raised, rheumatoid factor was positive and X-rays showed erosive changes in the small joints of the extremities. He was treated with diclofenac and sulphasalazine. Six months later he returned with an acutely tender, localized swelling on the dorsum of the right hand, clinically resembling a rheumatoid nodule or synovial thickening. Aspirated fluid contained red and white cells, but no crystals. Bacillus licheniformis was isolated but this was initially regarded as a
probable contaminant. The lesion persisted and the same organism was isolated from two further aspirates over the next 8 weeks. The patient then recalled an injury to the hand whilst at work several months earlier. The lesion was incised under local anaesthesia, and a 2.5 cm thorn was removed (Fig.). It was then felt that Bacillus licheniformis probably represented a secondary infection of the lesion, and the patient was treated with cotrimoxazole with complete healing of the wound. Prevalence of rheumatoid nodules ranges from 15 to 39% and 11% at presentation [1]. They are commonly subcutaneous and found in areas of mechanical stress such as the elbows and the front of the tibia but other sites such as the dorsum of the hand have been described [2]. Although usually asymptomatic, they may ulcerate to cause mechanical compression or even become infected [2]. Infection due to an organism of the Bacillus species is unusual and may follow penetrating injuries often involving a foreign body. This has been best described in the eye where Bacillus infection may produce severe conjunctivitis, keratitis, iritis or a fulminating panophthalmitis [3]. Bacillus species may also infect iatrogenic foreign bodies, such as ventriculoperitoneal shunts [4], renal dialysates [5] and prosthetic heart valves [6]. The definitive treatment is removal of any foreign body, whether accidentally or iatrogenically introduced. In the present patient, delay in diagnosis occurred because the organism, though isolated on several occasions, was thought to be a contaminant. However, when the foreign body was identified, then the pathogenic nature of Bacillus licheniformis was recognized, and appropriate antibiotic therapy eradicated the infection. Repeated isolation of a non-pathogenic organism from joints or soft tissues in a patient with RA should lead to a search for a foreign body. We are grateful for technical advice from Dr R. A. Swann, Consultant Microbiologist, Leicester Royal Infirmary and Mr J. Kramer, PHLS, Colindale, and to Ms Judy Noble for her secretarial assistance.
M. KLOCKARS,T. PETTERSSON,P. VILJA, R. VON ESSEN
Institute of Occupational Health, Helsinki; Fourth Department of Medicine, Helsinki University Hospital; Department of Anatomy, University of Tampere; Rheumatism Foundation Hospital, Heinola, Finland Received 4 April 1990 1. Thompson PW. Laboratory markers of joint inflammation and damage. Br J Rheumatol 1987 ;26:131-5. 2. Giusti G. Adenosine deaminase. In: Bergmayer HU, ed. Methodsofenzymaticanalysis. Vol. 2.2nded. New York, NY: Academic Press, 1974. 3. Vilja P, Krohn K,TuohimaaP. A rapid and sensitive non-competitive avidin-biotin assay for lactoferrin. J Immunol Methods 1985; 76:73-83. 4. Miles LEM, Lipschitz DA, Bieber CP, Cook JD. Measurement of serum ferritin by a 2-site immunoradiometnc assay. AnalBiochem 1974 ;61:209-24. 5. Blake DR, Bacon PA, Eastham EJ, Brigham K. Synovial fluid ferritin in rheumatoid arthritis. Br MedJ 1980;281:715-16. 6. Malmqvist J,Thorell Jl, Wollheim FA. Lactoferrin and lysozymein arthriticexudates. ActaMcdScand 1977;202:313-18. 7. Pettersson T, Klockars M, Weber TH, von Essen R. Adenosine deaminase activity in joint effusions. Scand J Rheumatoll980;W-.365-9. 8. Smiley DJ, Hoffman WL, Moore SE, Paradies LH. The humoral immune response of the rheumatoid synovium. Semin Arthritis Rheum 1985; 14:151-62. 9. Blake DR, Gallagher PJ, Potter AR, Bell MJ, Bacon PA. The effect of synovial iron on the progression of rheumatoid disease. Arthritis Rheum 1984;27:495-501.
10. Tritsch GL, Niswander PW. Adenosine deaminase activity and superoxide formation during phagocytosis and membrane perturbation of macrophages. Immunol Commun 9810l ll.Freemont AJ, Rutley C. Distribution of immunoglobulin heavy chains in diseased synovia. J Clin Pathol l9&6;39:13\-5. 12. Warren JS, Kunkel RG, Simon RH, Johnson KJ, Ward PA. Ultrastructural cytochemical analysis of oxygen radicalmediated immunoglobulin A immune complex induced lung injury in the rat. Lab Invest 1989;60:651-8. 13. KlockarsM,HedenborgM,KoistinenJ,IsobeT. IgG and IgA enhance the chrysotile induced production of reactive oxygen metabolites by human PMN. Clin Exp Immunol 1989;78:372-7.
Is this a Record? SIR—The patient whose pelvic X-ray is shown (Fig.) is a female age 72. She was diagnosed as having 'synovitis' of the knees aged 10. Despite this she continued with physical education at school and coped until the age of 16 when she had a severe attack of pain in the hips which precluded her sitting down and which was treated with 6 weeks of bed rest. The working diagnosis was rheumatoid arthritis and subsequent developments have supported this diagnosis. Aged 18 she was admitted to the Royal Bath Hospital in Harrogate on account of her hip pain and treated by Dr Yeoman with just one piece of advice that she remembers, namely 'never ride a horse'. Matters improved, in that she was able to go on a walking holiday to Switzerland age 21. During her in-patient stay she had received gold therapy (1935) and then had a further course as an in-patient towards the end of the war when she required a further inpatient admission for 6 months, being placed in a double abduction frame (Bradford Royal Infirmary). The Adams' prosthesis was inserted in 1953 by Mr James Wishart. (Prior to this the only prosthesis used was Petersen's and was not very satisfactory.) John CrawfordAdams devised the Adams' prosthesis, which on the outside was the diameter of the acetabulum but inside was much smaller and fitted the head of the femur. It was therefore considered particularly suitable for rheumatoid cases in which there had been considerable loss of bone from the femoral head. John Crawford-Adams fitted only about 40 of these and possibly 20 were satisfactory. The firm which made them was called Willens and is no longer in business. The right Charnley prosthesis was inserted in 1972 fol-
FIG.
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Michigan on June 28, 2015
All of the measured proteins, ferritin, lactoferrin, ADA and immunoglobulins, have been implicated as important contributors to the synovial inflammation [5-8]. ADA is a ubiquitous enzyme, with the greatest concentrations occurring in T-lymphocytes. Lactoferrin is released from neutrophilic granulocytes in acute infections and other inflammatory conditions, and cells of the mononuclear phagocyte system display the largest synthetic capacity of ferritin. In the rheumatoid joint, iron may promote inflammation by interaction with the cascade of reactive oxygen metabolites formed by polymorphonuclear leucocytes in the synovial fluid [9]. Even ADA has been suggested to interfere with oxygen free radical formation; macrophages generate superoxide radicals in direct proportion to their intracellular ADA activity [10]. A relatively high proportion of IgA-positive plasma cells in inflamed synovium has been observed, and it has been reported that these cells selectively enter the tissue under the specific local influence of T-helper cells [11]. Tissue injury induced by the IgA immune complex appears to be mediated by reactive oxygen metabolites [12]. For some phagocytic material, IgG and IgA enhance the formation of reactive oxygen metabolites by human polymorphonuclear leucocytes in vitro [13]. Local immunoglobulins may thus affect the potential tissue injury cascade of reactive oxygen metabolites produced by phagocytic cells within the joint. From the diagnostic point of view, our results are in agreement with reports stating that synovial fluid ferritin determination is not a suitable test for discriminating between rheumatic diseases of different aetiology. The observations that synovial fluid ADA concentrations are higher in patients with RA and reactive arthritis than in patients with O A and the demonstration that ADA activity in synovial fluid from patients with inflammatory arthritis correlates with general disease activity as measured by haemoglobin concentration and ESR may support the use of synovial fluid ADA determinations for the clinical follow-up of patients with inflammatory joint diseases.
319
3X)
BRITISH JOURNAL OF RHEUMATOLOGY VOL. XXIX NO. 4
lowing a fractured neck of femur by Mr Brian Hamilton when the patient was still under the care of Mr James Wishart. Current walking tolerance is 400 metres, limited more because of stiff knees. She does not require a walking aid. She feels that the left hip prosthesis has always functioned better than the later replacement on the right. WENDY DODDS
St Lukes Hospital, Bradford, W. Yorkshire BD5 ON A Received 5 April 1990 Infected Foreign Body due to Bacillus licheniformis in Rheumatoid Arthritis
L. A. T. DAVID, M. LYONS*, A. SAMANTA, M. PRENTICE*,
F. E. NICHOL
Departments of Rheumatology and * Microbiology, Leicester Royal Infirmary, Leicester LEI 5WW. Received 6 April 1990
I
I
i
FIG.—Thorn removed from the dorsum of the hand.
1. Kaye BR, Kaye RL, Bolsrove A. Rheumatoid nodules: review of a new classification, with a report of four seronegative cases. Am J Med 1984;76:279-92. 2. GardnerDL. In: Thepathologyofrheumatoid arthritis. Baltimore: Williams &Wilkins, 1972. 3. Davenport R, Smith C. Panophthalmitis due to an organism of the Bacillussubtilis group. Br J Ophthalmol 1952;36:389-92. 4. Raphael SS, Donaghue M. Infection due to Bacillus cereus. Can MedAssocJ 1976;115(3):207. 5. CurtisJR,WingAJ,ColemanJC. Bacilluscereus bacteraemia; a complication of intermittent haemodialysis. Lancet 1967;i:136. 6. Tuazon C, Murray H, Levy C, Solny M, Curtin J, Sheagren J. Serious infections from Bacillus species. JAMA 1979;241:1137-40.
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Michigan on June 28, 2015
SIR—Rheumatoid nodules or synovial or tendon swellings occur in at least 20% of patients with classical rheumatoid arthritis (RA). However, the differential diagnosis of subcutaneous nodules is wide, and even in established RA other causes should be excluded. We report a case in which infection of a subcutaneous foreign body with an unusual organism produced diagnostic confusion in a patient with RA. A 64-year-old farm worker initially presented with a 6-month history of early morning stiffness of wrists, symmetrical swelling of metacarpophalangeal, proximal interphalangeal, and metatarsophangeal joints. Plasma viscosity and C-reactive protein were raised, rheumatoid factor was positive and X-rays showed erosive changes in the small joints of the extremities. He was treated with diclofenac and sulphasalazine. Six months later he returned with an acutely tender, localized swelling on the dorsum of the right hand, clinically resembling a rheumatoid nodule or synovial thickening. Aspirated fluid contained red and white cells, but no crystals. Bacillus licheniformis was isolated but this was initially regarded as a
probable contaminant. The lesion persisted and the same organism was isolated from two further aspirates over the next 8 weeks. The patient then recalled an injury to the hand whilst at work several months earlier. The lesion was incised under local anaesthesia, and a 2.5 cm thorn was removed (Fig.). It was then felt that Bacillus licheniformis probably represented a secondary infection of the lesion, and the patient was treated with cotrimoxazole with complete healing of the wound. Prevalence of rheumatoid nodules ranges from 15 to 39% and 11% at presentation [1]. They are commonly subcutaneous and found in areas of mechanical stress such as the elbows and the front of the tibia but other sites such as the dorsum of the hand have been described [2]. Although usually asymptomatic, they may ulcerate to cause mechanical compression or even become infected [2]. Infection due to an organism of the Bacillus species is unusual and may follow penetrating injuries often involving a foreign body. This has been best described in the eye where Bacillus infection may produce severe conjunctivitis, keratitis, iritis or a fulminating panophthalmitis [3]. Bacillus species may also infect iatrogenic foreign bodies, such as ventriculoperitoneal shunts [4], renal dialysates [5] and prosthetic heart valves [6]. The definitive treatment is removal of any foreign body, whether accidentally or iatrogenically introduced. In the present patient, delay in diagnosis occurred because the organism, though isolated on several occasions, was thought to be a contaminant. However, when the foreign body was identified, then the pathogenic nature of Bacillus licheniformis was recognized, and appropriate antibiotic therapy eradicated the infection. Repeated isolation of a non-pathogenic organism from joints or soft tissues in a patient with RA should lead to a search for a foreign body. We are grateful for technical advice from Dr R. A. Swann, Consultant Microbiologist, Leicester Royal Infirmary and Mr J. Kramer, PHLS, Colindale, and to Ms Judy Noble for her secretarial assistance.
