Streptococcus milleri
Hemingway, Balfour, McCartney, Leiberman
Also, in a previous report from this centre, Strep. milleri was cultured from abscesses in three out of 15 drug addicts. 6 The pattern of infection in these Glasgow addicts who inject into the groin would appear therefore to be different from the previously reported American series. There may be several possible reasons for this difference. The usual drugs of addiction in the American series have been heroin or cocaine, whereas a combination of crushed buprenorphine (Temgesic) and temazepam is commonly abused by Glasgow drug addicts. These tablets are often crushed between the teeth, and the skin over the injection site cleaned with saliva. Strep. milleri is a frequent isolate from dental plaque 3,10 and this injection practice may account for the high incidence of this organism in abscesses. Groin injections are frequently used, not because of the large vessels present, but because the stigmata of injection are more readily concealed than after arm injection. Another possibility is that recent advances in microbiological techniques have allowed more accurate speciation of streptococci. Thus, rather than being more common, Strep. milleri may be simply more easily recognised than in the past. The patients presented in this report all had evidence of extensive abscesses or tissue destruction. This may be related to the production of the enzyme hyaluronidase which is produced by 83% of isolates of Strep. milleri from abscesses.f We believe this organism is an increasingly important pathogen in intravenous drug abusers. Its presence is frequently associated with extensive abscess cavities which require thorough surgical drainage. The recognised association of Strep. milleri with other organisms, especially anaerobes.' indicates that multiple antimicrobial therapy may be necessary. In addition, any antibiotic therapy should be aimed at reducing the risk of
potentially fatal endocarditis, which is a common sequel to bacteraemic episodes with Strep. milleri and is associated with a high incidence of septic complications? We suggest a combination therapy of benzyl penicillin and metronidazole with or without an animoglycoaside. Septic complications of intravenous drug abuse are becoming increasingly common and some of the most serious infections have been associated with the unusual mouth commensal Strep. milleri. ACKNOWLEDGEMENT: We thank Mr I.G. Finlay and Mr R Swan for permission to report patients under their care. REFERENCES Crane LR, Levine DP, Zervos Mj. Bacteraernia in narcotic addicts at the Detroit medical centre.i. Microbiology, epidemiology, risk factors and empiric therapy. Reviews ofInfectious Diseases 1986; 8(2): 364-373. 2 Crane LR, Levine DP, Zervos MI. Bacteraemia in narcotic addicts at the Detroit medical centre. ii. Infectious endocarditis: Aprospective comparative study. Reviews of Infectious Diseases 1986; 8: 374-3%. 3 Gossling J. Occurence and pathogenicity of the Streptococcus milleri group. Reviews of Infectious Diseases 1988; 10: 257-285. 4 Shlaes DM, Lerner PI, Wolinski E, Gopalakrishna KV. Infections due to Lancefield group F and related streptococci. Medicine 1981; 60: 197-207. 5 Muller F, von Graevenitz A, Ferber T. Streptococcus milleri subcutaneous abscesses in drug addicts. Infection 1987; 15: 201. 6 Fullerton GM. Soft tissue infections in drug abusers presentingto an accident and emergency department. Health Bulletin 1983; 41/6: 296-299. 7 Murray HW, Gross KC, Masur H, Roberts RB. Serious infections caused by Streptococcus milleri. Am J Medicine 1978; 64: 759-764. 8 Unsworth PF. Hyaluronidase production in Streptococcus milleri in relation to infection. J Clin Pathol1989; 42: 506-510. 9 Vander Auwera P. Clinical significance of Streptococcus milleri. Eur J Clin Microbiol1985; 4: 386-390. 10 Whitworth JM. Lancefie1d Group F and related streptococci.J MedMicrobiol 1990; 33: 135-151.
0036-9330/92/13891/117 $2.00 in USA © 1992 Scottish Medical Journal
Scot Med J 1992; 37: 117-118
ASTROCYTOMA PRESENTING WITH VASCULITIS GP. Leese, R.T. lung, KD. Morley. Department of Medicine, Ninewells Hospital and Medical School, Dundee.
Abstract: A cerebral astrocytoma which had remained quiescent possibly for 12 years, presented with blackouts, vasculitis and a lupus-like (L-E like) syndrome. The association between tumours and "L-E like" syndromes is reviewed briefly. Keywords: Cerebral tumour, vasculitis, S.L.E.
Introduction
T
umours may present with non-metastatic manifestations although this rarely, if ever, occurs with primary cerebral tumours. We describe a case of a connective-tissue disorder which may be associated with an astrocytoma.
Case report In 1978, a 35 year old female nurse presented with a photosensitive rash Correspondence to: Dr G P Leese, Department of Medicine, Ninewells Hospital and Medical School, Dundee DD1 9SY.
on her face and hands. She had a normochromic normocytic anaemia of 109/dl, thrombocytopenia of 90x109/l, and a normal white cell count 9 (5.5x10 /1). Her ESR was elevated at 60mm/hr. The antinuclear antibody was negative and the C4 level slightly reduced at 21mg/dl (NR=25-50mg/dl). Skin biopsy from affected skin showed histological change compatible with an allergic vasculitis. The rash settled with prednisolone at an initial dose of 15mg daily, which was reduced to zero over the next six months. The following year there was a further exacerbation of the rash at which time the antinuclear antibody titre was significantly positive. Repeat skin biopsy was consistent with but not diagnostic of systemic lupus erythematosus (SLE). The rash settled with prednisolone 20mg oral and azathioprine lOOmg daily, both of which
117
Astrocytoma presenting with vasculitis
were slowly reduced and eventually withdrawn over the following three years without recurrence of symptoms. Eight years later in 1990, the patient presented again with a photosensitive rash, arthralgia, Raynaud's phenomenon and onycholysis. Investigations revealed; a normal full blood count (Hb=14.2g/dl); ESR=22mm/hr; immunopathology negative (rheumatoid factor, antinuclear antibody, antibody to extractable nuclear antigens, antineutrophilcytoplasmic antibody and anticentromere antibody); low C3(76mg/dl); negative cold agglutinins and cryoglobulins. Chest X-ray was normal. All symptoms and signs improved after starting prednisolone 30mg and azathioprine 100mg daily. The prednisolone was gradually reduced to 10mg daily. The ESR remained between 20-30mm/hr. Four months later, the patient was readmitted with a three day history of severe headaches and two blackouts. She was very drowsy, had bilateral papilloedemabutno localising neurological signs. CT brain scan revealed marked generalised cerebral oedema and a lesion which was thought to be a haematoma in the right parietal region. After three weeks with no improvement on high dose dexamethasone (16mg later reduced to 8mg daily) a stereotatic brain biopsy was performed in the right parietal lobe and histology showed a well differentiated diffusely infiltrating astrocytoma which was not surgically resectable. The patient was started on sodium valproate for focal seizures and given a course of radiotherapy, with some clinical and radiological improvement. At the time of writing, eight months later, the rash was absent and the headaches were well controlled.
Discussion This patient whilst not having the classic features of SLE had a 13 year history of 'lupus-like' syndrome with vasculitis, arthralgia, photosensitivity, Raynaud's phenomenon, positive antinuclear antibodies and reduced complement levels. Lupus-like syndromes have been associated with malignancy of . 1 myxomas,5 t h e stomac h.cervi .cervix,1 ovary, 2 breast,3 kid ney, 4 atna 6 and sarcomas. Other connective tissue disorders such as scleroderma have a well established link with breast carcinoma? Vasculitides and in particular the lupus-like syndrome, have not, to our knowledge, previously been associated with primary cerebral tumours. Immune complex formation and tissue deposition is thought to be the main pathophysiological mechanism causing vasculitis in SLE, and malignant tumours could be the source of antigen within such immune complexes/' In this case, the vasculitis may have been a paraneoplastic manifestation of the astrocytoma, possibly mediated by immune complex deposition. Alternatively, the astrocytoma may have
118
Leese, Jung, Morley
been secondary to the connective-tissue disorder or the treatment. Although controversial, it has been postulated that patients with connective-tissue disease have an increased risk of malignancy.f but these are usually reticuloendothelial in origin and in patients on imm uno suppressive drugs. The occurrence of the astrocytoma and vasculitis may also have been coincidental. In our patient, the vasculitis predated documentation of the malignancy, although this may reflect a late diagnosis of a slowly . astrocytoma. I ' growmg n preVIOUS cases 13456 ' , , " TO t he rna liIgnancy was usually well established before the vasculitis developed, sometimes occurring soon after treatment, perhaps corresponding with a time of antigen release. It is conceivable, but impossible to prove, that the initial vasculitis 12 years previously could have heralded the onset of the well differentiated astrocytoma, which is k nown to b e a s1ow-growing . tumour. 11 IS This case demonstrates an interesting presentation of a cerebral astrocytoma. It is possible that the astrocytoma and lupus-like syndrome may have been associated. To our knowledge this has not been reported previously. REFERENCES
2 3
4 5 6 7 8 9
10
11
Mackenzie AH, Scherbel AL. Connective tissue syndromes associated with carcinoma. Geriatrics 1963; 18: 745. Bennett R, Ginsberg M, Thomsen S. Carcinomapolyarthritis. The presenting symptoms of an ovarian tumour and association with platelet activating factor. Arthritis Rheum 1976; 19: 953. Pierce DA, Stem R, Jaffee R, Zulman J, Talal N. Imrnunoblastic carcinoma with features of Sjorgrens syndrome and systemic lupus erythematosus in a patient with immunoblastic lymphadenopathy. Arthritis Rheum 1979; 22: 911. Marcus R, Grayzel A. A lupus antibody syndrome associated with hypernephroma. Arthritis Rheum 1979; 22: 1395 Byrd W, Matthews O. Left atrial myxoma presenting as a systemic vaxculitis. Arthritis Rheum 1980; 23: 240 Wallach HW. Lupus-like syndrome associated with carcinoma of the breast. Arch Int Med 1977; 137: 532. Forbes AM, Woodrow JC, Verbov JL, Graham RM. Carcinoma of breast and scleroderma: four further cases and a literature review. Br J Rheum 1989; 28: 65. Saverlick R, Lawley T. Cutaneous vasculitis: Its relationship to systemic disease. Med Clinics N America 1989; 73: 1221 Caldwell DS. Musculoskeletal syndromes associated with malignancy in "Textbook of Rheumatology" Edit Kelly W, Harris E, Ruddy S, Sledge C (1989). Miyachi H, Akizuki M, Yamagata H, Minori T, Yoshida S, Homma M. Hypertrophic osteoarthropathy, cutaneous vasculitis and mixed-type cryoglobinulinemia in a patient with nasopharyngeal carcinoma. Arthritis Rheum 1987; 30: 825. Gunderson CH. Brain tumours. In: Essentials of Clinical Neurology pub. 1990.
Hemingway, Balfour, McCartney, Leiberman
Also, in a previous report from this centre, Strep. milleri was cultured from abscesses in three out of 15 drug addicts. 6 The pattern of infection in these Glasgow addicts who inject into the groin would appear therefore to be different from the previously reported American series. There may be several possible reasons for this difference. The usual drugs of addiction in the American series have been heroin or cocaine, whereas a combination of crushed buprenorphine (Temgesic) and temazepam is commonly abused by Glasgow drug addicts. These tablets are often crushed between the teeth, and the skin over the injection site cleaned with saliva. Strep. milleri is a frequent isolate from dental plaque 3,10 and this injection practice may account for the high incidence of this organism in abscesses. Groin injections are frequently used, not because of the large vessels present, but because the stigmata of injection are more readily concealed than after arm injection. Another possibility is that recent advances in microbiological techniques have allowed more accurate speciation of streptococci. Thus, rather than being more common, Strep. milleri may be simply more easily recognised than in the past. The patients presented in this report all had evidence of extensive abscesses or tissue destruction. This may be related to the production of the enzyme hyaluronidase which is produced by 83% of isolates of Strep. milleri from abscesses.f We believe this organism is an increasingly important pathogen in intravenous drug abusers. Its presence is frequently associated with extensive abscess cavities which require thorough surgical drainage. The recognised association of Strep. milleri with other organisms, especially anaerobes.' indicates that multiple antimicrobial therapy may be necessary. In addition, any antibiotic therapy should be aimed at reducing the risk of
potentially fatal endocarditis, which is a common sequel to bacteraemic episodes with Strep. milleri and is associated with a high incidence of septic complications? We suggest a combination therapy of benzyl penicillin and metronidazole with or without an animoglycoaside. Septic complications of intravenous drug abuse are becoming increasingly common and some of the most serious infections have been associated with the unusual mouth commensal Strep. milleri. ACKNOWLEDGEMENT: We thank Mr I.G. Finlay and Mr R Swan for permission to report patients under their care. REFERENCES Crane LR, Levine DP, Zervos Mj. Bacteraernia in narcotic addicts at the Detroit medical centre.i. Microbiology, epidemiology, risk factors and empiric therapy. Reviews ofInfectious Diseases 1986; 8(2): 364-373. 2 Crane LR, Levine DP, Zervos MI. Bacteraemia in narcotic addicts at the Detroit medical centre. ii. Infectious endocarditis: Aprospective comparative study. Reviews of Infectious Diseases 1986; 8: 374-3%. 3 Gossling J. Occurence and pathogenicity of the Streptococcus milleri group. Reviews of Infectious Diseases 1988; 10: 257-285. 4 Shlaes DM, Lerner PI, Wolinski E, Gopalakrishna KV. Infections due to Lancefield group F and related streptococci. Medicine 1981; 60: 197-207. 5 Muller F, von Graevenitz A, Ferber T. Streptococcus milleri subcutaneous abscesses in drug addicts. Infection 1987; 15: 201. 6 Fullerton GM. Soft tissue infections in drug abusers presentingto an accident and emergency department. Health Bulletin 1983; 41/6: 296-299. 7 Murray HW, Gross KC, Masur H, Roberts RB. Serious infections caused by Streptococcus milleri. Am J Medicine 1978; 64: 759-764. 8 Unsworth PF. Hyaluronidase production in Streptococcus milleri in relation to infection. J Clin Pathol1989; 42: 506-510. 9 Vander Auwera P. Clinical significance of Streptococcus milleri. Eur J Clin Microbiol1985; 4: 386-390. 10 Whitworth JM. Lancefie1d Group F and related streptococci.J MedMicrobiol 1990; 33: 135-151.
0036-9330/92/13891/117 $2.00 in USA © 1992 Scottish Medical Journal
Scot Med J 1992; 37: 117-118
ASTROCYTOMA PRESENTING WITH VASCULITIS GP. Leese, R.T. lung, KD. Morley. Department of Medicine, Ninewells Hospital and Medical School, Dundee.
Abstract: A cerebral astrocytoma which had remained quiescent possibly for 12 years, presented with blackouts, vasculitis and a lupus-like (L-E like) syndrome. The association between tumours and "L-E like" syndromes is reviewed briefly. Keywords: Cerebral tumour, vasculitis, S.L.E.
Introduction
T
umours may present with non-metastatic manifestations although this rarely, if ever, occurs with primary cerebral tumours. We describe a case of a connective-tissue disorder which may be associated with an astrocytoma.
Case report In 1978, a 35 year old female nurse presented with a photosensitive rash Correspondence to: Dr G P Leese, Department of Medicine, Ninewells Hospital and Medical School, Dundee DD1 9SY.
on her face and hands. She had a normochromic normocytic anaemia of 109/dl, thrombocytopenia of 90x109/l, and a normal white cell count 9 (5.5x10 /1). Her ESR was elevated at 60mm/hr. The antinuclear antibody was negative and the C4 level slightly reduced at 21mg/dl (NR=25-50mg/dl). Skin biopsy from affected skin showed histological change compatible with an allergic vasculitis. The rash settled with prednisolone at an initial dose of 15mg daily, which was reduced to zero over the next six months. The following year there was a further exacerbation of the rash at which time the antinuclear antibody titre was significantly positive. Repeat skin biopsy was consistent with but not diagnostic of systemic lupus erythematosus (SLE). The rash settled with prednisolone 20mg oral and azathioprine lOOmg daily, both of which
117
Astrocytoma presenting with vasculitis
were slowly reduced and eventually withdrawn over the following three years without recurrence of symptoms. Eight years later in 1990, the patient presented again with a photosensitive rash, arthralgia, Raynaud's phenomenon and onycholysis. Investigations revealed; a normal full blood count (Hb=14.2g/dl); ESR=22mm/hr; immunopathology negative (rheumatoid factor, antinuclear antibody, antibody to extractable nuclear antigens, antineutrophilcytoplasmic antibody and anticentromere antibody); low C3(76mg/dl); negative cold agglutinins and cryoglobulins. Chest X-ray was normal. All symptoms and signs improved after starting prednisolone 30mg and azathioprine 100mg daily. The prednisolone was gradually reduced to 10mg daily. The ESR remained between 20-30mm/hr. Four months later, the patient was readmitted with a three day history of severe headaches and two blackouts. She was very drowsy, had bilateral papilloedemabutno localising neurological signs. CT brain scan revealed marked generalised cerebral oedema and a lesion which was thought to be a haematoma in the right parietal region. After three weeks with no improvement on high dose dexamethasone (16mg later reduced to 8mg daily) a stereotatic brain biopsy was performed in the right parietal lobe and histology showed a well differentiated diffusely infiltrating astrocytoma which was not surgically resectable. The patient was started on sodium valproate for focal seizures and given a course of radiotherapy, with some clinical and radiological improvement. At the time of writing, eight months later, the rash was absent and the headaches were well controlled.
Discussion This patient whilst not having the classic features of SLE had a 13 year history of 'lupus-like' syndrome with vasculitis, arthralgia, photosensitivity, Raynaud's phenomenon, positive antinuclear antibodies and reduced complement levels. Lupus-like syndromes have been associated with malignancy of . 1 myxomas,5 t h e stomac h.cervi .cervix,1 ovary, 2 breast,3 kid ney, 4 atna 6 and sarcomas. Other connective tissue disorders such as scleroderma have a well established link with breast carcinoma? Vasculitides and in particular the lupus-like syndrome, have not, to our knowledge, previously been associated with primary cerebral tumours. Immune complex formation and tissue deposition is thought to be the main pathophysiological mechanism causing vasculitis in SLE, and malignant tumours could be the source of antigen within such immune complexes/' In this case, the vasculitis may have been a paraneoplastic manifestation of the astrocytoma, possibly mediated by immune complex deposition. Alternatively, the astrocytoma may have
118
Leese, Jung, Morley
been secondary to the connective-tissue disorder or the treatment. Although controversial, it has been postulated that patients with connective-tissue disease have an increased risk of malignancy.f but these are usually reticuloendothelial in origin and in patients on imm uno suppressive drugs. The occurrence of the astrocytoma and vasculitis may also have been coincidental. In our patient, the vasculitis predated documentation of the malignancy, although this may reflect a late diagnosis of a slowly . astrocytoma. I ' growmg n preVIOUS cases 13456 ' , , " TO t he rna liIgnancy was usually well established before the vasculitis developed, sometimes occurring soon after treatment, perhaps corresponding with a time of antigen release. It is conceivable, but impossible to prove, that the initial vasculitis 12 years previously could have heralded the onset of the well differentiated astrocytoma, which is k nown to b e a s1ow-growing . tumour. 11 IS This case demonstrates an interesting presentation of a cerebral astrocytoma. It is possible that the astrocytoma and lupus-like syndrome may have been associated. To our knowledge this has not been reported previously. REFERENCES
2 3
4 5 6 7 8 9
10
11
Mackenzie AH, Scherbel AL. Connective tissue syndromes associated with carcinoma. Geriatrics 1963; 18: 745. Bennett R, Ginsberg M, Thomsen S. Carcinomapolyarthritis. The presenting symptoms of an ovarian tumour and association with platelet activating factor. Arthritis Rheum 1976; 19: 953. Pierce DA, Stem R, Jaffee R, Zulman J, Talal N. Imrnunoblastic carcinoma with features of Sjorgrens syndrome and systemic lupus erythematosus in a patient with immunoblastic lymphadenopathy. Arthritis Rheum 1979; 22: 911. Marcus R, Grayzel A. A lupus antibody syndrome associated with hypernephroma. Arthritis Rheum 1979; 22: 1395 Byrd W, Matthews O. Left atrial myxoma presenting as a systemic vaxculitis. Arthritis Rheum 1980; 23: 240 Wallach HW. Lupus-like syndrome associated with carcinoma of the breast. Arch Int Med 1977; 137: 532. Forbes AM, Woodrow JC, Verbov JL, Graham RM. Carcinoma of breast and scleroderma: four further cases and a literature review. Br J Rheum 1989; 28: 65. Saverlick R, Lawley T. Cutaneous vasculitis: Its relationship to systemic disease. Med Clinics N America 1989; 73: 1221 Caldwell DS. Musculoskeletal syndromes associated with malignancy in "Textbook of Rheumatology" Edit Kelly W, Harris E, Ruddy S, Sledge C (1989). Miyachi H, Akizuki M, Yamagata H, Minori T, Yoshida S, Homma M. Hypertrophic osteoarthropathy, cutaneous vasculitis and mixed-type cryoglobinulinemia in a patient with nasopharyngeal carcinoma. Arthritis Rheum 1987; 30: 825. Gunderson CH. Brain tumours. In: Essentials of Clinical Neurology pub. 1990.
