British Journal of Rheumatology 1992;31:715-720
LETTERS TO THE EDITOR
R. A. WATTS, D. G. I. SCOTT,* A. J. CRISP
Rheumatology Research Unit, Addenbrooke's Hospital, Cambridge; * Department of Rheumatology, Norfolk and Norwich Hospital, Norwich Accepted 26 June 1992 1. SagherF, Evans-PazZ. Mastocytosis and the mastcell. BasekS. Karger, 1967. 2. Travis WD, Li C, Bergstrahl EJ, Yam LT, Swee RG. Systemic mast cell disease: analysis of 58 cases and literature review. Medicine 1988;67:345-68. 3. Graves L, Stechschulte DJ, Morris DC, Lukert BP. Inhibition of mediator release in systemic masocytosis is associated with reversal of bone changes. J Bone Miner Res 1990,5:1113-9. 4. Alexander RR. Disodium cromoglycate in the treatment of systemic mastocytosis involving only bone. Ada Haematol (Basel) 1985;74:108-10. 5. Cundy T, Beneton MHC, Darby AJ, Marshall WJ, Kanis J A. Osteopaenia in systemic mastocytosis: natural history and responses to treatment with inhibitors of bone resorption. Bone 1987 ;8:149-55. 6. Chines A, Pacifici R, Avioli LV, Teitlbaum SC, Korenblat PE. Systemic mastocytosis presenting as osteoporosis. A clinical and histomorphometric study. J Clin Endocrinol Metab 1991; 72:140-4. Transdermal Fungal Implantation Causing an Infectious Arthritis
SIR—The many species of Aspergillus are ubiquitous fungi of low virulence [1]. When they do cause opportunistic disease in humans this is usually pulmonary. Bone and joint infection with Aspergillus is extremely rare and occurs predominantly in immunocompromised individuals [2]. We describe a healthy patient who developed a monarthritis as a result of an unusual transdermal fungal implantation. A 47-year-old farmer presented with a gradual onset of pain and swelling in his left knee. His knees were subject to numerous minor abrasions during the course of a normal working day but he gave no history of significant trauma, nor of locking or giving way. He had had no recent diarrhoea, urethritis, conjunctivitis or rashes and had no relevant family or social history. Apart from an inflamed left knee with a tense effusion and wasting of the quadriceps, physical examination was normal. The plasma viscosity was raised at 1.89 cp and the white cell count (WCC) was 15.2 x 109/l with 76% granulocytes. The straw coloured synovial fluid was slightly turbid with 3+ leucocytes present but both primary culture and broth subculture were negative, on this and two subsequent occasions. No crystals were seen. Mid-stream urine examination was normal 715
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Michigan on June 17, 2015
to a further vertebral collapse and treatment with the HI and H2 antagonists astemizole and ranitidine and Estraderm was instituted. Oral and intravenous clodronate have been used in a single patient with osteoporosis and SMCD [5]. They did not observe a sustained remission with intravenous clodronate, however, oral clodronate reduced the urinary hydroxyproline excretion together with the serum alkaline phosphatase and calcium, suggesting that both bone resorption and formation were inhibited [5]. We feel that bisphosphonates are potentially useful in this condition, however the data are limited and it is possible that a greater effect might be observed with different dose regimens.
Mastocytosis and Osteoporosis
SIR—Systemic mast cell disease (SMCD) is an uncommon condition characterized by abnormal proliferation of mast cells, which usually presents with the typical skin rash, urticaria pigmentosa. Radiological evidence of bone disease is present in 70% of patients [1,2] but presentation with symptomatic osteoporosis is less frequent (16%) [2]. Treatment for skeletal involvement is limited, with good responses to ketotifen [3]; disodium cromoglycate [4] and clodronate [5] being reported in single cases. We describe a patient who presented with rapidly progressive osteoporosis secondary to SMCD and discuss the response to bisphosphonate therapy. A 52-year-old woman presented with a 2-month history of thoracic pain. A hysterectomy with ovarian preservation had been performed 5 years earlier. There was an 8 year history of a pigmented rash over the arms and legs. Physical examination revealed a marked thoracic kyphosis. There were small papular pigmented lesions over the arms and legs typical of urticaria pigmentosa which became nodular after scratching. General physical examination was unremarkable. Plain radiographs of the thoracic and lumbar spine showed osteoporosis with wedging of several thoracic vertebrae. Bone densitometry (Hologic QDR 1000) confirmed osteoporosis with a trochanteric density of 0.461 g/cm2 (70% age matched controls) and vertebral density (L1-L4) of 0.602 g/cm2 (57%). The full blood count serum biochemistry were normal and the ESR 19 mm/h (Westergren). A skin biopsy demonstrated the presence of numerous mast cells in the dermis and confirmed the diagnosis of urticaria pigmentosa. Bone marrow aspirate was normal apart from a significantly increased number of mast cells. She received a single infusion of 60 mg disodium pamidronate, which resulted in significant improvement of bone pain for 4 months before a further vertebral fracture occurred. There was no significant change in bone density or in the rate of bone loss as determined by non-fasting 24-h urinary calcium and hydroxyproline excretion over this period. She has subsequently been treated with the HI and H2 antagonists astemizole and ranitidine, in addition to Estraderm 50. After 15 months there had been improvement in both trochanteric density (0.478 g/cm2, 73%) and vertebral density (0.697 g/cm2, 75%). Systemic mastocytosis is a rare cause of generalized osteoporosis. Our patient presented with rapidly progressive osteoporosis with crush fractures. Bone loss in these patients is due to a higher than normal rate of bone resorption, which exceeds the rate of bone formation even though the formation rates were normal [5,6]. Osteoporosis arising from this mechanism ought to be amenable to treatment with inhibitors of bone formation. We treated our patient with intravenous disodium pamidronate, with symptomatic relief for 4 months. There was no evidence of decreased bone resorption as judged by urinary calcium and hydroxyproline measurements or in bone density after treatment, although the duration of follow-up was only 4 months before intervention with other drugs able to alter bone metabolism. At that time pain recurred probably due
716
BRITISH JOURNAL OF RHEUMATOLOGY VOL. XXXI NO. 10
FIG. 1.—Section of the synovial biopsy showing heavy inflammatory infiltrate containing lymphocytes, plasma cells and occasional giant cells surrounding a nidus of fungal hyphae which are septate and branching (final magnification x200).
Although the fungus was not cultured, histologically it was seen to be in its invasive form and surrounded by an intense granulomatous inflammatory reaction, thus suggesting a causative role. The morphology is suggestive of an atypical Aspergillus but histology alone cannot exclude the possibility of Sporotrichosis schenkii, a true pathogen [5,6]. The rare reported skeletal Aspergillus infections usually occur in relation to a wound [3,4]. We suggest that the frequent abrasive trauma to the legs evident in this farmer forced a hair together with the fungus into the synovium of the knee, where it was able to set up a focus of infection. H. G. TAYLOR, F. E. NICHOL, E. H. MACKAY, P. SHELDON
Department of Rheumatology, Leicester Royal Infirmary, Leicester LEI 5WW A ccepted 26 June 1992 1. Rippon JW. Aspergillosis. In: Rippon JW., eds. Medical mycology. 3rdedn. Philadelphia: WB Saunders. 1988:618-50.
2. Hoffman GS. Mycobacterial and fungal infections of bone and joints. In: Kelley WN, Harris ED, Ruddy S, Sledge CB, eds. Textbook of rheumatology, 2nd edn. Philadelphia: WB Saunders, 1985:1527-40. 3. Yacobucci GN, Santilli MD. Sporotrichosis of the knee. A case report. Orthopaedics 1986;9:387-90. 4. Downs NJ, Hinthorn DR, Mhatre VR, Liu C. Intra-articular amphotericin B treatment of Sporothrix schenkii arthritis. ArcK Intern Med 1989;149:954-5. 5. Corral CJ, Merz WG, Rekedal K, Hughes WT. Aspergillus osteomyelitis in an immunocompetent adolescent: a case report and review of the literature. Pediatrics 1982;70:455-61. 6. Tack KJ, Rhame FS, Brown B, Thompson RC. Aspergillus osteomyelitis. Report of four cases and review of the literature. ,4m 7 Medl 982;73:295-300. Viruses and Rheumatic Disease
SIR—Deighton, Madeley and Walker [1] stated some implications consequent upon their lack of positive findings in a study of antiviral antibodies in rheumatoid arthritis discordant HLA-identical same-sexed sibling pairs and concluded that 'further research would have to be approached in a different way'. Their suggestions seem to tie in with the details of an editorial by Openshaw on dual infections [2] and some earlier epidemiological observations [3] and from evidence summarized in a textbook chapter on infectious arthritis [4] which taken in conjunction may afford some specific advice for further research. The editorial mentioned that several types of viral infection including adenovirus seemed to be able to precipitate meningococcal meningitis in previously asymptomatic subjects in Chad whose meningococcal carriage had originated via pilgrims returning from Mecca. The effect of adenovirus and echovirus in provoking staphylococcal shedding was also mentioned. As part of the control group for an epidemiological back pain study of 6886 men in London [3] the rheumatic sickness absence group (back and neck pain excluded) were noted to show a peak of sickness absence which followed upon peaks of viral infection including adenovirus 7 and echoviruses 9 and 11 identified from the Colindale Infectious Diseases Surveillance centre records. Yet again these same viruses (adenovirus 7 and echoviruses 9 and 11) were singled out amongst a few others in a textbook review of anecdotal isolations of virus is acute arthritis [4]. The repeat identification of these same viruses does seem to imply that they may variously be responsible for precipitating disease in primed and genetically susceptible individuals. It may be that several events are required to coincide, possibly in a specific order, and within a given time interval. The second infection may have to occur at the right interval after the first infection though with chronic carriage of the priming agent, the time interval might not be so critical. It may be that these constraints explain the sporadic onset of arthritis ('end result disease'). Population density might well increase the risk of such double infection and explain why Soloman, Robin and Valkenburg were to show more rheumatoid arthritis in urban than rural areas [5]. With regard to the observations of Deighton et al. it may explain why both of a matched pair may have been exposed to a virus and have developed antibodies (to adenovirus for example) and yet only one go on to develop the disease because only one had the priming agent. To explain their lack of positive findings they postulated that different viral triggers may be important in different individuals, that the virus may have a 'hit-and-run' role, and that incomplete humoral responses may be implicated.
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Michigan on June 17, 2015
and stool culture for Salmonella, Shigella, Yersinia and Campylobacter negative. Antibody titres against Salmonella typhi and paratyphi and Yersinia enterocolitica and pseudotuberculosis were normal as was the serum urea, creatinine and urate levels. Aspiration and steroid injection on two occasions gave incomplete and short-lived relief only. An empirical course of antibiotics from his general practitioner and non-steroidal anti-inflammatory drugs had no effect. An arthroscopic examination was performed 5 months later and a biopsy taken from the floridly inflamed synovial tissue. Histology of this tissue revealed a severe active chronic synovitis with a focus of fungal infiltration by an atypical Aspergillus species (Fig. 1). Microscopy and culture of this tissue for bacteria (including Mycobacterium tuberculosis) was negative. His plasma viscosity and WCC remained elevated and an X-ray of his knee showed the presence of an effusion and patchy osteopaenia of the patella and periarticular regions of the femur. A synovectomy was performed 6 weeks later. Histology of this tissue confirmed an active granulomatous inflammatory process and in addition revealed a human hair embedded in the synovial tissue. The patient remains well 6 months following the synovectomy with good function in the knee and satisfactory recovery of quadriceps bulk.
LETTERS TO THE EDITOR
R. A. WATTS, D. G. I. SCOTT,* A. J. CRISP
Rheumatology Research Unit, Addenbrooke's Hospital, Cambridge; * Department of Rheumatology, Norfolk and Norwich Hospital, Norwich Accepted 26 June 1992 1. SagherF, Evans-PazZ. Mastocytosis and the mastcell. BasekS. Karger, 1967. 2. Travis WD, Li C, Bergstrahl EJ, Yam LT, Swee RG. Systemic mast cell disease: analysis of 58 cases and literature review. Medicine 1988;67:345-68. 3. Graves L, Stechschulte DJ, Morris DC, Lukert BP. Inhibition of mediator release in systemic masocytosis is associated with reversal of bone changes. J Bone Miner Res 1990,5:1113-9. 4. Alexander RR. Disodium cromoglycate in the treatment of systemic mastocytosis involving only bone. Ada Haematol (Basel) 1985;74:108-10. 5. Cundy T, Beneton MHC, Darby AJ, Marshall WJ, Kanis J A. Osteopaenia in systemic mastocytosis: natural history and responses to treatment with inhibitors of bone resorption. Bone 1987 ;8:149-55. 6. Chines A, Pacifici R, Avioli LV, Teitlbaum SC, Korenblat PE. Systemic mastocytosis presenting as osteoporosis. A clinical and histomorphometric study. J Clin Endocrinol Metab 1991; 72:140-4. Transdermal Fungal Implantation Causing an Infectious Arthritis
SIR—The many species of Aspergillus are ubiquitous fungi of low virulence [1]. When they do cause opportunistic disease in humans this is usually pulmonary. Bone and joint infection with Aspergillus is extremely rare and occurs predominantly in immunocompromised individuals [2]. We describe a healthy patient who developed a monarthritis as a result of an unusual transdermal fungal implantation. A 47-year-old farmer presented with a gradual onset of pain and swelling in his left knee. His knees were subject to numerous minor abrasions during the course of a normal working day but he gave no history of significant trauma, nor of locking or giving way. He had had no recent diarrhoea, urethritis, conjunctivitis or rashes and had no relevant family or social history. Apart from an inflamed left knee with a tense effusion and wasting of the quadriceps, physical examination was normal. The plasma viscosity was raised at 1.89 cp and the white cell count (WCC) was 15.2 x 109/l with 76% granulocytes. The straw coloured synovial fluid was slightly turbid with 3+ leucocytes present but both primary culture and broth subculture were negative, on this and two subsequent occasions. No crystals were seen. Mid-stream urine examination was normal 715
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Michigan on June 17, 2015
to a further vertebral collapse and treatment with the HI and H2 antagonists astemizole and ranitidine and Estraderm was instituted. Oral and intravenous clodronate have been used in a single patient with osteoporosis and SMCD [5]. They did not observe a sustained remission with intravenous clodronate, however, oral clodronate reduced the urinary hydroxyproline excretion together with the serum alkaline phosphatase and calcium, suggesting that both bone resorption and formation were inhibited [5]. We feel that bisphosphonates are potentially useful in this condition, however the data are limited and it is possible that a greater effect might be observed with different dose regimens.
Mastocytosis and Osteoporosis
SIR—Systemic mast cell disease (SMCD) is an uncommon condition characterized by abnormal proliferation of mast cells, which usually presents with the typical skin rash, urticaria pigmentosa. Radiological evidence of bone disease is present in 70% of patients [1,2] but presentation with symptomatic osteoporosis is less frequent (16%) [2]. Treatment for skeletal involvement is limited, with good responses to ketotifen [3]; disodium cromoglycate [4] and clodronate [5] being reported in single cases. We describe a patient who presented with rapidly progressive osteoporosis secondary to SMCD and discuss the response to bisphosphonate therapy. A 52-year-old woman presented with a 2-month history of thoracic pain. A hysterectomy with ovarian preservation had been performed 5 years earlier. There was an 8 year history of a pigmented rash over the arms and legs. Physical examination revealed a marked thoracic kyphosis. There were small papular pigmented lesions over the arms and legs typical of urticaria pigmentosa which became nodular after scratching. General physical examination was unremarkable. Plain radiographs of the thoracic and lumbar spine showed osteoporosis with wedging of several thoracic vertebrae. Bone densitometry (Hologic QDR 1000) confirmed osteoporosis with a trochanteric density of 0.461 g/cm2 (70% age matched controls) and vertebral density (L1-L4) of 0.602 g/cm2 (57%). The full blood count serum biochemistry were normal and the ESR 19 mm/h (Westergren). A skin biopsy demonstrated the presence of numerous mast cells in the dermis and confirmed the diagnosis of urticaria pigmentosa. Bone marrow aspirate was normal apart from a significantly increased number of mast cells. She received a single infusion of 60 mg disodium pamidronate, which resulted in significant improvement of bone pain for 4 months before a further vertebral fracture occurred. There was no significant change in bone density or in the rate of bone loss as determined by non-fasting 24-h urinary calcium and hydroxyproline excretion over this period. She has subsequently been treated with the HI and H2 antagonists astemizole and ranitidine, in addition to Estraderm 50. After 15 months there had been improvement in both trochanteric density (0.478 g/cm2, 73%) and vertebral density (0.697 g/cm2, 75%). Systemic mastocytosis is a rare cause of generalized osteoporosis. Our patient presented with rapidly progressive osteoporosis with crush fractures. Bone loss in these patients is due to a higher than normal rate of bone resorption, which exceeds the rate of bone formation even though the formation rates were normal [5,6]. Osteoporosis arising from this mechanism ought to be amenable to treatment with inhibitors of bone formation. We treated our patient with intravenous disodium pamidronate, with symptomatic relief for 4 months. There was no evidence of decreased bone resorption as judged by urinary calcium and hydroxyproline measurements or in bone density after treatment, although the duration of follow-up was only 4 months before intervention with other drugs able to alter bone metabolism. At that time pain recurred probably due
716
BRITISH JOURNAL OF RHEUMATOLOGY VOL. XXXI NO. 10
FIG. 1.—Section of the synovial biopsy showing heavy inflammatory infiltrate containing lymphocytes, plasma cells and occasional giant cells surrounding a nidus of fungal hyphae which are septate and branching (final magnification x200).
Although the fungus was not cultured, histologically it was seen to be in its invasive form and surrounded by an intense granulomatous inflammatory reaction, thus suggesting a causative role. The morphology is suggestive of an atypical Aspergillus but histology alone cannot exclude the possibility of Sporotrichosis schenkii, a true pathogen [5,6]. The rare reported skeletal Aspergillus infections usually occur in relation to a wound [3,4]. We suggest that the frequent abrasive trauma to the legs evident in this farmer forced a hair together with the fungus into the synovium of the knee, where it was able to set up a focus of infection. H. G. TAYLOR, F. E. NICHOL, E. H. MACKAY, P. SHELDON
Department of Rheumatology, Leicester Royal Infirmary, Leicester LEI 5WW A ccepted 26 June 1992 1. Rippon JW. Aspergillosis. In: Rippon JW., eds. Medical mycology. 3rdedn. Philadelphia: WB Saunders. 1988:618-50.
2. Hoffman GS. Mycobacterial and fungal infections of bone and joints. In: Kelley WN, Harris ED, Ruddy S, Sledge CB, eds. Textbook of rheumatology, 2nd edn. Philadelphia: WB Saunders, 1985:1527-40. 3. Yacobucci GN, Santilli MD. Sporotrichosis of the knee. A case report. Orthopaedics 1986;9:387-90. 4. Downs NJ, Hinthorn DR, Mhatre VR, Liu C. Intra-articular amphotericin B treatment of Sporothrix schenkii arthritis. ArcK Intern Med 1989;149:954-5. 5. Corral CJ, Merz WG, Rekedal K, Hughes WT. Aspergillus osteomyelitis in an immunocompetent adolescent: a case report and review of the literature. Pediatrics 1982;70:455-61. 6. Tack KJ, Rhame FS, Brown B, Thompson RC. Aspergillus osteomyelitis. Report of four cases and review of the literature. ,4m 7 Medl 982;73:295-300. Viruses and Rheumatic Disease
SIR—Deighton, Madeley and Walker [1] stated some implications consequent upon their lack of positive findings in a study of antiviral antibodies in rheumatoid arthritis discordant HLA-identical same-sexed sibling pairs and concluded that 'further research would have to be approached in a different way'. Their suggestions seem to tie in with the details of an editorial by Openshaw on dual infections [2] and some earlier epidemiological observations [3] and from evidence summarized in a textbook chapter on infectious arthritis [4] which taken in conjunction may afford some specific advice for further research. The editorial mentioned that several types of viral infection including adenovirus seemed to be able to precipitate meningococcal meningitis in previously asymptomatic subjects in Chad whose meningococcal carriage had originated via pilgrims returning from Mecca. The effect of adenovirus and echovirus in provoking staphylococcal shedding was also mentioned. As part of the control group for an epidemiological back pain study of 6886 men in London [3] the rheumatic sickness absence group (back and neck pain excluded) were noted to show a peak of sickness absence which followed upon peaks of viral infection including adenovirus 7 and echoviruses 9 and 11 identified from the Colindale Infectious Diseases Surveillance centre records. Yet again these same viruses (adenovirus 7 and echoviruses 9 and 11) were singled out amongst a few others in a textbook review of anecdotal isolations of virus is acute arthritis [4]. The repeat identification of these same viruses does seem to imply that they may variously be responsible for precipitating disease in primed and genetically susceptible individuals. It may be that several events are required to coincide, possibly in a specific order, and within a given time interval. The second infection may have to occur at the right interval after the first infection though with chronic carriage of the priming agent, the time interval might not be so critical. It may be that these constraints explain the sporadic onset of arthritis ('end result disease'). Population density might well increase the risk of such double infection and explain why Soloman, Robin and Valkenburg were to show more rheumatoid arthritis in urban than rural areas [5]. With regard to the observations of Deighton et al. it may explain why both of a matched pair may have been exposed to a virus and have developed antibodies (to adenovirus for example) and yet only one go on to develop the disease because only one had the priming agent. To explain their lack of positive findings they postulated that different viral triggers may be important in different individuals, that the virus may have a 'hit-and-run' role, and that incomplete humoral responses may be implicated.
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Michigan on June 17, 2015
and stool culture for Salmonella, Shigella, Yersinia and Campylobacter negative. Antibody titres against Salmonella typhi and paratyphi and Yersinia enterocolitica and pseudotuberculosis were normal as was the serum urea, creatinine and urate levels. Aspiration and steroid injection on two occasions gave incomplete and short-lived relief only. An empirical course of antibiotics from his general practitioner and non-steroidal anti-inflammatory drugs had no effect. An arthroscopic examination was performed 5 months later and a biopsy taken from the floridly inflamed synovial tissue. Histology of this tissue revealed a severe active chronic synovitis with a focus of fungal infiltration by an atypical Aspergillus species (Fig. 1). Microscopy and culture of this tissue for bacteria (including Mycobacterium tuberculosis) was negative. His plasma viscosity and WCC remained elevated and an X-ray of his knee showed the presence of an effusion and patchy osteopaenia of the patella and periarticular regions of the femur. A synovectomy was performed 6 weeks later. Histology of this tissue confirmed an active granulomatous inflammatory process and in addition revealed a human hair embedded in the synovial tissue. The patient remains well 6 months following the synovectomy with good function in the knee and satisfactory recovery of quadriceps bulk.
