Nancy Walsh

GLASGOW, SCOTLAND — Subclinical atherosclerosis is common among patients early in the course of inflammatory polyarthritis, even among those not considered to be otherwise at high risk for cardiovascular disease, Diane K. Bunn reported at the annual meeting of the British Society for Rheumatology.

Increased awareness of the excess mortality—primarily from cardiac causes—associated with rheumatoid and undifferentiated arthritis prompted institution of the Norfolk Arthritis Register, a primary-care-based inception cohort of patients with inflammatory polyarthritis, according to Ms. Bunn of Norfolk and Norwich (England) University Hospital.

The register now has enrolled 93 patients, 61 of whom are female. On recruitment, patients underwent baseline assessments of medication history and comorbidities. A cardiac risk profile that includes measurement of fasting lipids and glucose, blood pressure, height, and weight also was performed.

In addition, patients underwent a duplex ultrasound examination of the carotid arteries using a B-mode Doppler.

Median age of the cohort was 50 years, and median disease duration at presentation was 7 months. On recruitment, 56 (60%) were taking disease-modifying antirheumatic drugs, and 59 (63%) were taking NSAIDs. Among this latter group, 12 were being treated with coxibs and the remainder with traditional nonsteroidals.

Blood pressure was 140/90 or higher in 31 (33%), but only 7 were taking antihypertensive medication. Fasting cholesterol was 5.1 mmol or more in 44 (47%), yet only 3 (2 of whom were known diabetics) were taking a statin drug, she wrote in a poster session. A total of 16 (17.2%) were smokers.

Cardiovascular risk, calculated using the Joint British Societies Cardiac Risk Assessor (www.bnf.org/BNF/extra/current/450024.htm

The finding that a large proportion of the cohort had subclinical atherosclerosis early in their disease highlights the importance of considering cardiovascular risk right from the start in patients with inflammatory polyarthritis, she concluded.

“Further follow-up of this cohort will help quantify atheroma progression and, in particular, how inflammation, metabolic factors, and therapy contribute to the process in early inflammatorypolyarthritis,” she wrote.

GLASGOW, SCOTLAND — Subclinical atherosclerosis is common among patients early in the course of inflammatory polyarthritis, even among those not considered to be otherwise at high risk for cardiovascular disease, Diane K. Bunn reported at the annual meeting of the British Society for Rheumatology.

Increased awareness of the excess mortality—primarily from cardiac causes—associated with rheumatoid and undifferentiated arthritis prompted institution of the Norfolk Arthritis Register, a primary-care-based inception cohort of patients with inflammatory polyarthritis, according to Ms. Bunn of Norfolk and Norwich (England) University Hospital.

The register now has enrolled 93 patients, 61 of whom are female. On recruitment, patients underwent baseline assessments of medication history and comorbidities. A cardiac risk profile that includes measurement of fasting lipids and glucose, blood pressure, height, and weight also was performed.

In addition, patients underwent a duplex ultrasound examination of the carotid arteries using a B-mode Doppler.

Median age of the cohort was 50 years, and median disease duration at presentation was 7 months. On recruitment, 56 (60%) were taking disease-modifying antirheumatic drugs, and 59 (63%) were taking NSAIDs. Among this latter group, 12 were being treated with coxibs and the remainder with traditional nonsteroidals.

Blood pressure was 140/90 or higher in 31 (33%), but only 7 were taking antihypertensive medication. Fasting cholesterol was 5.1 mmol or more in 44 (47%), yet only 3 (2 of whom were known diabetics) were taking a statin drug, she wrote in a poster session. A total of 16 (17.2%) were smokers.

Cardiovascular risk, calculated using the Joint British Societies Cardiac Risk Assessor (www.bnf.org/BNF/extra/current/450024.htm

The finding that a large proportion of the cohort had subclinical atherosclerosis early in their disease highlights the importance of considering cardiovascular risk right from the start in patients with inflammatory polyarthritis, she concluded.

“Further follow-up of this cohort will help quantify atheroma progression and, in particular, how inflammation, metabolic factors, and therapy contribute to the process in early inflammatorypolyarthritis,” she wrote.

GLASGOW, SCOTLAND — Subclinical atherosclerosis is common among patients early in the course of inflammatory polyarthritis, even among those not considered to be otherwise at high risk for cardiovascular disease, Diane K. Bunn reported at the annual meeting of the British Society for Rheumatology.

Increased awareness of the excess mortality—primarily from cardiac causes—associated with rheumatoid and undifferentiated arthritis prompted institution of the Norfolk Arthritis Register, a primary-care-based inception cohort of patients with inflammatory polyarthritis, according to Ms. Bunn of Norfolk and Norwich (England) University Hospital.

The register now has enrolled 93 patients, 61 of whom are female. On recruitment, patients underwent baseline assessments of medication history and comorbidities. A cardiac risk profile that includes measurement of fasting lipids and glucose, blood pressure, height, and weight also was performed.

In addition, patients underwent a duplex ultrasound examination of the carotid arteries using a B-mode Doppler.

Median age of the cohort was 50 years, and median disease duration at presentation was 7 months. On recruitment, 56 (60%) were taking disease-modifying antirheumatic drugs, and 59 (63%) were taking NSAIDs. Among this latter group, 12 were being treated with coxibs and the remainder with traditional nonsteroidals.

Blood pressure was 140/90 or higher in 31 (33%), but only 7 were taking antihypertensive medication. Fasting cholesterol was 5.1 mmol or more in 44 (47%), yet only 3 (2 of whom were known diabetics) were taking a statin drug, she wrote in a poster session. A total of 16 (17.2%) were smokers.

Cardiovascular risk, calculated using the Joint British Societies Cardiac Risk Assessor (www.bnf.org/BNF/extra/current/450024.htm

The finding that a large proportion of the cohort had subclinical atherosclerosis early in their disease highlights the importance of considering cardiovascular risk right from the start in patients with inflammatory polyarthritis, she concluded.

“Further follow-up of this cohort will help quantify atheroma progression and, in particular, how inflammation, metabolic factors, and therapy contribute to the process in early inflammatorypolyarthritis,” she wrote.

GLASGOW, SCOTLAND — Subclinical atherosclerosis is common among patients early in the course of inflammatory polyarthritis, even among those not considered to be otherwise at high risk for cardiovascular disease, Diane K. Bunn reported at the annual meeting of the British Society for Rheumatology.

Increased awareness of the excess mortality associated with rheumatoid and undifferentiated arthritis prompted institution of the Norfolk Arthritis Register, a primary-care-based inception cohort of patients with inflammatory polyarthritis, according to Ms. Bunn of Norfolk and Norwich (England) University Hospital.

The register now has enrolled 93 patients, 61 of whom are female. Median age of the cohort was 50 years, and median disease duration at presentation was 7 months. On recruitment, 56 (60%) were taking disease-modifying antirheumatic drugs, and 59 (63%) were taking nonsteroidal anti-inflammatory drugs. Among this latter group, 12 were being treated with coxibs and the remainder with NSAIDs.

Blood pressure was 140/90 or higher in 31 (33%), but only 7 were taking antihypertensive medication. Fasting cholesterol was 5.1 mmol or more in 44 (47%), yet only 3 (2 of whom were known diabetics) were taking a statin drug, she wrote in a poster session. Sixteen (17.2%) were smokers.

Cardiovascular risk, calculated using the Joint British Societies Cardiac Risk Assessor (www.bnf.org/BNF/extra/current/450024.htm

The finding that a large proportion of the cohort had subclinical atherosclerosis early in the course of their disease highlights the importance of considering cardiovascular risk right from the start in patients with inflammatory polyarthritis, she concluded.

GLASGOW, SCOTLAND — Subclinical atherosclerosis is common among patients early in the course of inflammatory polyarthritis, even among those not considered to be otherwise at high risk for cardiovascular disease, Diane K. Bunn reported at the annual meeting of the British Society for Rheumatology.

Increased awareness of the excess mortality associated with rheumatoid and undifferentiated arthritis prompted institution of the Norfolk Arthritis Register, a primary-care-based inception cohort of patients with inflammatory polyarthritis, according to Ms. Bunn of Norfolk and Norwich (England) University Hospital.

The register now has enrolled 93 patients, 61 of whom are female. Median age of the cohort was 50 years, and median disease duration at presentation was 7 months. On recruitment, 56 (60%) were taking disease-modifying antirheumatic drugs, and 59 (63%) were taking nonsteroidal anti-inflammatory drugs. Among this latter group, 12 were being treated with coxibs and the remainder with NSAIDs.

Blood pressure was 140/90 or higher in 31 (33%), but only 7 were taking antihypertensive medication. Fasting cholesterol was 5.1 mmol or more in 44 (47%), yet only 3 (2 of whom were known diabetics) were taking a statin drug, she wrote in a poster session. Sixteen (17.2%) were smokers.

Cardiovascular risk, calculated using the Joint British Societies Cardiac Risk Assessor (www.bnf.org/BNF/extra/current/450024.htm

The finding that a large proportion of the cohort had subclinical atherosclerosis early in the course of their disease highlights the importance of considering cardiovascular risk right from the start in patients with inflammatory polyarthritis, she concluded.

GLASGOW, SCOTLAND — Subclinical atherosclerosis is common among patients early in the course of inflammatory polyarthritis, even among those not considered to be otherwise at high risk for cardiovascular disease, Diane K. Bunn reported at the annual meeting of the British Society for Rheumatology.

Increased awareness of the excess mortality associated with rheumatoid and undifferentiated arthritis prompted institution of the Norfolk Arthritis Register, a primary-care-based inception cohort of patients with inflammatory polyarthritis, according to Ms. Bunn of Norfolk and Norwich (England) University Hospital.

The register now has enrolled 93 patients, 61 of whom are female. Median age of the cohort was 50 years, and median disease duration at presentation was 7 months. On recruitment, 56 (60%) were taking disease-modifying antirheumatic drugs, and 59 (63%) were taking nonsteroidal anti-inflammatory drugs. Among this latter group, 12 were being treated with coxibs and the remainder with NSAIDs.

Blood pressure was 140/90 or higher in 31 (33%), but only 7 were taking antihypertensive medication. Fasting cholesterol was 5.1 mmol or more in 44 (47%), yet only 3 (2 of whom were known diabetics) were taking a statin drug, she wrote in a poster session. Sixteen (17.2%) were smokers.

Cardiovascular risk, calculated using the Joint British Societies Cardiac Risk Assessor (www.bnf.org/BNF/extra/current/450024.htm

The finding that a large proportion of the cohort had subclinical atherosclerosis early in the course of their disease highlights the importance of considering cardiovascular risk right from the start in patients with inflammatory polyarthritis, she concluded.

GLASGOW, SCOTLAND — Shoulder involvement is often overlooked in ankylosing spondylitis, despite patients' reports that upper body pain interferes with their daily activities, Dr. Charlotte E. Page reported in a poster session at the annual meeting of the British Society for Rheumatology.

Among a group of 31 ankylosing spondylitis (AS) patients attending a 2-week physiotherapy program who responded to questionnaires about their symptoms, 12 reported current shoulder pain, while 10 patients reported experiencing shoulder pain in the past, reported Dr. Page of the rheumatology department of University Hospital of Wales, Cardiff. The patients, aged 17–62 years, had a mean AS duration of 19 years.

Among patients with current shoulder pain, four reported bilateral symptoms, and nine indicated that their daily activities were affected. Among those with previous pain, three study patients reported that their shoulder involvement continued to interfere with their daily activities, noted Dr. Page.

The reported prevalence of shoulder pain among the general population is approximately 12%, and estimates among those with AS range from 7% to 33%, she noted. “Our prevalence of 39% is slightly higher, probably reflecting the type of patients who attend intensive physiotherapy programs.”

Only 10 of the 22 patients who had either current or past shoulder pain had undergone one or more radiologic investigations. Eight had been evaluated with plain radiographs, three with ultrasound, and three with MRI arthrograms.

Among the eight patients who had received one or more corticosteroid injections to the shoulder region, five reported still having shoulder pain and six reported still experiencing symptoms that interfered with daily activities. Among the seven who had received physiotherapy directed at their shoulder symptoms, five continued to experience pain.

Specific physiotherapy and corticosteroid injections had therefore been given to only 32% and 36% of patients, respectively, and had not alleviated the symptoms in the majority, she noted.

Moreover, a total of 26 patients reported peripheral joint involvement other than the shoulder. Despite this, only six patients received disease-modifying antirheumatic drugs or anti-tumor necrosis factor-α therapy, which suggests an underappreciation of the extent of AS patients' peripheral joint pain, according to Dr. Page.

Much of the shoulder involvement was rotator cuff tendonitis, which can be imaged and treated, Dr. Page said in an interview. Patients should be asked specifically about this, she said.

“We all know about their hip pain but we seem to forget about the top half” of the body, she said.

GLASGOW, SCOTLAND — Shoulder involvement is often overlooked in ankylosing spondylitis, despite patients' reports that upper body pain interferes with their daily activities, Dr. Charlotte E. Page reported in a poster session at the annual meeting of the British Society for Rheumatology.

Among a group of 31 ankylosing spondylitis (AS) patients attending a 2-week physiotherapy program who responded to questionnaires about their symptoms, 12 reported current shoulder pain, while 10 patients reported experiencing shoulder pain in the past, reported Dr. Page of the rheumatology department of University Hospital of Wales, Cardiff. The patients, aged 17–62 years, had a mean AS duration of 19 years.

Among patients with current shoulder pain, four reported bilateral symptoms, and nine indicated that their daily activities were affected. Among those with previous pain, three study patients reported that their shoulder involvement continued to interfere with their daily activities, noted Dr. Page.

The reported prevalence of shoulder pain among the general population is approximately 12%, and estimates among those with AS range from 7% to 33%, she noted. “Our prevalence of 39% is slightly higher, probably reflecting the type of patients who attend intensive physiotherapy programs.”

Only 10 of the 22 patients who had either current or past shoulder pain had undergone one or more radiologic investigations. Eight had been evaluated with plain radiographs, three with ultrasound, and three with MRI arthrograms.

Among the eight patients who had received one or more corticosteroid injections to the shoulder region, five reported still having shoulder pain and six reported still experiencing symptoms that interfered with daily activities. Among the seven who had received physiotherapy directed at their shoulder symptoms, five continued to experience pain.

Specific physiotherapy and corticosteroid injections had therefore been given to only 32% and 36% of patients, respectively, and had not alleviated the symptoms in the majority, she noted.

Moreover, a total of 26 patients reported peripheral joint involvement other than the shoulder. Despite this, only six patients received disease-modifying antirheumatic drugs or anti-tumor necrosis factor-α therapy, which suggests an underappreciation of the extent of AS patients' peripheral joint pain, according to Dr. Page.

Much of the shoulder involvement was rotator cuff tendonitis, which can be imaged and treated, Dr. Page said in an interview. Patients should be asked specifically about this, she said.

“We all know about their hip pain but we seem to forget about the top half” of the body, she said.

GLASGOW, SCOTLAND — Shoulder involvement is often overlooked in ankylosing spondylitis, despite patients' reports that upper body pain interferes with their daily activities, Dr. Charlotte E. Page reported in a poster session at the annual meeting of the British Society for Rheumatology.

Among a group of 31 ankylosing spondylitis (AS) patients attending a 2-week physiotherapy program who responded to questionnaires about their symptoms, 12 reported current shoulder pain, while 10 patients reported experiencing shoulder pain in the past, reported Dr. Page of the rheumatology department of University Hospital of Wales, Cardiff. The patients, aged 17–62 years, had a mean AS duration of 19 years.

Among patients with current shoulder pain, four reported bilateral symptoms, and nine indicated that their daily activities were affected. Among those with previous pain, three study patients reported that their shoulder involvement continued to interfere with their daily activities, noted Dr. Page.

The reported prevalence of shoulder pain among the general population is approximately 12%, and estimates among those with AS range from 7% to 33%, she noted. “Our prevalence of 39% is slightly higher, probably reflecting the type of patients who attend intensive physiotherapy programs.”

Only 10 of the 22 patients who had either current or past shoulder pain had undergone one or more radiologic investigations. Eight had been evaluated with plain radiographs, three with ultrasound, and three with MRI arthrograms.

Among the eight patients who had received one or more corticosteroid injections to the shoulder region, five reported still having shoulder pain and six reported still experiencing symptoms that interfered with daily activities. Among the seven who had received physiotherapy directed at their shoulder symptoms, five continued to experience pain.

Specific physiotherapy and corticosteroid injections had therefore been given to only 32% and 36% of patients, respectively, and had not alleviated the symptoms in the majority, she noted.

Moreover, a total of 26 patients reported peripheral joint involvement other than the shoulder. Despite this, only six patients received disease-modifying antirheumatic drugs or anti-tumor necrosis factor-α therapy, which suggests an underappreciation of the extent of AS patients' peripheral joint pain, according to Dr. Page.

Much of the shoulder involvement was rotator cuff tendonitis, which can be imaged and treated, Dr. Page said in an interview. Patients should be asked specifically about this, she said.

“We all know about their hip pain but we seem to forget about the top half” of the body, she said.

Diagnosis: Bullous Pemphigoid

A 27-year-old otherwise healthy man presented with a 2-day history of pruritic blisters that were scattered on the trunk and proximal extremities. Two weeks after admission, oral mucous membrane lesions developed, the patient complained of pain on swallowing, and the skin involvement had increased to 90% of the body surface area. Histology revealed a subepidermal blister with a superficial, perivascular infiltrate with eosinophils, lymphocytes, and neutrophils. Numerous eosinophils were present in the blister cavity, and direct immunofluorescence showed linear staining of IgG, IgA, and C3 along the basal membrane. ELISA showed the presence of IgG autoantibodies against bullous pemphigoid antigen 2 (BPAG2, 180 kd), but none against bullous pemphigoid antigen 1 (BPAG1, 230 kd), said Dr. Amanda S. Buchau of the dermatology department at Heinrich Heine University, Düsseldorf, Germany with mucosal involvement in 10%–20% of cases. The condition may result from an increased expression of anti-BP-180 autoantibodies, which are considered a marker of poor prognosis in bullous pemphigoid.

This patient was treated with methylprednisolone up to 160 mg/day for 3 weeks, along with pulse cyclophosphamide 1,000 mg, without response. His antibody titer also remained very high, so plasmapheresis was performed. Treatment with 250 mg/day of prednisone and 1 g of mycophenolate mofetil twice daily stabilized the disease, and he was given ciprofloxacin, dicloxacillin, and piperacillin to prevent infections, as well as antihistamines and topical steroids to alleviate pruritus.

Dr. Buchau presented this case at a congress on skin, rheumatism, and autoimmunity held in Abano Terme, Italy.

The otherwise healthy man presented with a 2-day history of pruritic blisters across the trunk and proximal extremities.

Histology revealed a subepidermal blister with a perivascular infiltrate with eosinophils, lymphocytes, and neutrophils. Photos courtesy Dr. Amanda S. Buchau

Diagnosis: Bullous Pemphigoid

A 27-year-old otherwise healthy man presented with a 2-day history of pruritic blisters that were scattered on the trunk and proximal extremities. Two weeks after admission, oral mucous membrane lesions developed, the patient complained of pain on swallowing, and the skin involvement had increased to 90% of the body surface area. Histology revealed a subepidermal blister with a superficial, perivascular infiltrate with eosinophils, lymphocytes, and neutrophils. Numerous eosinophils were present in the blister cavity, and direct immunofluorescence showed linear staining of IgG, IgA, and C3 along the basal membrane. ELISA showed the presence of IgG autoantibodies against bullous pemphigoid antigen 2 (BPAG2, 180 kd), but none against bullous pemphigoid antigen 1 (BPAG1, 230 kd), said Dr. Amanda S. Buchau of the dermatology department at Heinrich Heine University, Düsseldorf, Germany with mucosal involvement in 10%–20% of cases. The condition may result from an increased expression of anti-BP-180 autoantibodies, which are considered a marker of poor prognosis in bullous pemphigoid.

This patient was treated with methylprednisolone up to 160 mg/day for 3 weeks, along with pulse cyclophosphamide 1,000 mg, without response. His antibody titer also remained very high, so plasmapheresis was performed. Treatment with 250 mg/day of prednisone and 1 g of mycophenolate mofetil twice daily stabilized the disease, and he was given ciprofloxacin, dicloxacillin, and piperacillin to prevent infections, as well as antihistamines and topical steroids to alleviate pruritus.

Dr. Buchau presented this case at a congress on skin, rheumatism, and autoimmunity held in Abano Terme, Italy.

The otherwise healthy man presented with a 2-day history of pruritic blisters across the trunk and proximal extremities.

Histology revealed a subepidermal blister with a perivascular infiltrate with eosinophils, lymphocytes, and neutrophils. Photos courtesy Dr. Amanda S. Buchau

Diagnosis: Bullous Pemphigoid

A 27-year-old otherwise healthy man presented with a 2-day history of pruritic blisters that were scattered on the trunk and proximal extremities. Two weeks after admission, oral mucous membrane lesions developed, the patient complained of pain on swallowing, and the skin involvement had increased to 90% of the body surface area. Histology revealed a subepidermal blister with a superficial, perivascular infiltrate with eosinophils, lymphocytes, and neutrophils. Numerous eosinophils were present in the blister cavity, and direct immunofluorescence showed linear staining of IgG, IgA, and C3 along the basal membrane. ELISA showed the presence of IgG autoantibodies against bullous pemphigoid antigen 2 (BPAG2, 180 kd), but none against bullous pemphigoid antigen 1 (BPAG1, 230 kd), said Dr. Amanda S. Buchau of the dermatology department at Heinrich Heine University, Düsseldorf, Germany with mucosal involvement in 10%–20% of cases. The condition may result from an increased expression of anti-BP-180 autoantibodies, which are considered a marker of poor prognosis in bullous pemphigoid.

This patient was treated with methylprednisolone up to 160 mg/day for 3 weeks, along with pulse cyclophosphamide 1,000 mg, without response. His antibody titer also remained very high, so plasmapheresis was performed. Treatment with 250 mg/day of prednisone and 1 g of mycophenolate mofetil twice daily stabilized the disease, and he was given ciprofloxacin, dicloxacillin, and piperacillin to prevent infections, as well as antihistamines and topical steroids to alleviate pruritus.

Dr. Buchau presented this case at a congress on skin, rheumatism, and autoimmunity held in Abano Terme, Italy.

The otherwise healthy man presented with a 2-day history of pruritic blisters across the trunk and proximal extremities.

Histology revealed a subepidermal blister with a perivascular infiltrate with eosinophils, lymphocytes, and neutrophils. Photos courtesy Dr. Amanda S. Buchau

GLASGOW, SCOTLAND — Joint hypermobility syndrome is profoundly underdiagnosed and its impact underestimated despite its being one of the most common causes of widespread chronic pain—and indeed may be the most common rheumatic disorder, Dr. Rodney Grahame said at the annual meeting of the British Society for Rheumatology (BSR).

“I looked at a series of 500 unselected new patients referred to the rheumatology clinic at Willesden Community Hospital in London between 2003 and 2005, evaluating them for their rheumatic complaints but also to see how many fit the JHS [joint hypermobility syndrome] phenotype. What I found exceeded my expectations by several orders of magnitude—overall, 45% of patients fulfilled the criteria,” Dr. Grahame said.

In contrast with his findings, “many of our rheumatology colleagues consider JHS to be rather trivial and relatively uncommon, and in a survey we did of all the BSR members, most said they diagnosed, on average, approximately 10 new cases each year, and half rated the impact on patients' lives as fairly minimal,” he said (Rheumatology [Oxford] 2001;40:559–62).

Extrapolating from those data would suggest that if most rheumatologists are diagnosing only 10 cases per year, they are identifying only 4.5% of cases. “That means that in England, 103,568 cases are missed annually, as are 593,930 cases in the United States. These are appalling statistics,” he said.

Evaluation of joint hypermobility traditionally is done using the Beighton scoring system, said Dr. Grahame, who was involved in the development of what are known as the revised Beighton criteria. The Beighton score identifies symptoms such as the ability to passively dorsiflex the fifth metacarpophalangeal joint to 90 degrees or more, to oppose the thumb to the volar aspect of the ipsilateral forearm, or to place the hands flat on the floor without bending the knees. This system is less than reliable in pauciarticular hypermobility, however, which is often the case in JHS. A common misconception is that hypermobility requires the involvement of four or more joints. In fact, only one joint need be hypermobile in JHS, he said.

Other typical presenting symptoms include acute or chronic pain and joint clicking. There may be a history of subluxations or dislocations, because the laxity of the ligaments leads to joint instability. Pain avoidance, typically beginning in childhood or adolescence, often leads to muscle deconditioning. Cutaneous findings include stretchability, paper-thin scars, and stretch marks. Ocular involvement can manifest with drooping eyelids and blue sclerae. Anxiety and other psychological disturbances such as phobias are common.

It has become increasingly clear that autonomic disturbances also play a significant role in the syndrome, according to Dr. Alan Hakim, another speaker at the meeting, who heads a hypermobility clinic at Whipps Cross University Hospital, London.

Three types of autonomic disturbances are predominant: syncopal, cardiorespiratory, and gastrointestinal. “It's phenomenal how many patients report presyncopal symptoms such as faintness and dizziness,” Dr. Hakim said. In one series of 48 patients with JHS, 78% were found to have orthostatic hypotension, postural orthostatic tachycardia syndrome, or orthostatic intolerance (Am. J. Med. 2003;115:33–40).

Cardiorespiratory findings include shortness of breath, while the gastrointestinal problems are similar to those seen in irritable bowel syndrome. Approximately 30% of patients report at least one autonomic disturbance, 20% have two, and 13%–14% report three autonomic disturbances, Dr. Hakim said.

Joint hypermobility syndrome is a genetically determined disorder of matrix proteins that is characterized by articular hyperextension, skin changes, marfanoid body habitus, and other manifestations such as hernias and varicose veins. It is considered benign, in that it does not significantly alter life expectancy, but affects quality of life and may be associated with frequent dislocations and early osteoarthritis and osteoporosis.

JHS manifests an autosomal dominant pattern of inheritance, with affected persons expressing varying degrees of joint laxity and other symptoms (Best Pract. Res. Clin. Rheumatol. 2003;17:989–1004). Women are affected approximately three times more commonly than men are.

Hyperextensibility of the finger joint is typical of hypermobility syndrome. A common misconception is that the diagnosis requires the involvement of four or more joints. In fact, only one joint need be hypermobile.

Excessive stretchiness of skin is associated with hypermobility syndrome. Paper-thin scars and stretch marks are other common cutaneous findings. Photos courtesy Dr. Rodney Grahame

GLASGOW, SCOTLAND — Joint hypermobility syndrome is profoundly underdiagnosed and its impact underestimated despite its being one of the most common causes of widespread chronic pain—and indeed may be the most common rheumatic disorder, Dr. Rodney Grahame said at the annual meeting of the British Society for Rheumatology (BSR).

“I looked at a series of 500 unselected new patients referred to the rheumatology clinic at Willesden Community Hospital in London between 2003 and 2005, evaluating them for their rheumatic complaints but also to see how many fit the JHS [joint hypermobility syndrome] phenotype. What I found exceeded my expectations by several orders of magnitude—overall, 45% of patients fulfilled the criteria,” Dr. Grahame said.

In contrast with his findings, “many of our rheumatology colleagues consider JHS to be rather trivial and relatively uncommon, and in a survey we did of all the BSR members, most said they diagnosed, on average, approximately 10 new cases each year, and half rated the impact on patients' lives as fairly minimal,” he said (Rheumatology [Oxford] 2001;40:559–62).

Extrapolating from those data would suggest that if most rheumatologists are diagnosing only 10 cases per year, they are identifying only 4.5% of cases. “That means that in England, 103,568 cases are missed annually, as are 593,930 cases in the United States. These are appalling statistics,” he said.

Evaluation of joint hypermobility traditionally is done using the Beighton scoring system, said Dr. Grahame, who was involved in the development of what are known as the revised Beighton criteria. The Beighton score identifies symptoms such as the ability to passively dorsiflex the fifth metacarpophalangeal joint to 90 degrees or more, to oppose the thumb to the volar aspect of the ipsilateral forearm, or to place the hands flat on the floor without bending the knees. This system is less than reliable in pauciarticular hypermobility, however, which is often the case in JHS. A common misconception is that hypermobility requires the involvement of four or more joints. In fact, only one joint need be hypermobile in JHS, he said.

Other typical presenting symptoms include acute or chronic pain and joint clicking. There may be a history of subluxations or dislocations, because the laxity of the ligaments leads to joint instability. Pain avoidance, typically beginning in childhood or adolescence, often leads to muscle deconditioning. Cutaneous findings include stretchability, paper-thin scars, and stretch marks. Ocular involvement can manifest with drooping eyelids and blue sclerae. Anxiety and other psychological disturbances such as phobias are common.

It has become increasingly clear that autonomic disturbances also play a significant role in the syndrome, according to Dr. Alan Hakim, another speaker at the meeting, who heads a hypermobility clinic at Whipps Cross University Hospital, London.

Three types of autonomic disturbances are predominant: syncopal, cardiorespiratory, and gastrointestinal. “It's phenomenal how many patients report presyncopal symptoms such as faintness and dizziness,” Dr. Hakim said. In one series of 48 patients with JHS, 78% were found to have orthostatic hypotension, postural orthostatic tachycardia syndrome, or orthostatic intolerance (Am. J. Med. 2003;115:33–40).

Cardiorespiratory findings include shortness of breath, while the gastrointestinal problems are similar to those seen in irritable bowel syndrome. Approximately 30% of patients report at least one autonomic disturbance, 20% have two, and 13%–14% report three autonomic disturbances, Dr. Hakim said.

Joint hypermobility syndrome is a genetically determined disorder of matrix proteins that is characterized by articular hyperextension, skin changes, marfanoid body habitus, and other manifestations such as hernias and varicose veins. It is considered benign, in that it does not significantly alter life expectancy, but affects quality of life and may be associated with frequent dislocations and early osteoarthritis and osteoporosis.

JHS manifests an autosomal dominant pattern of inheritance, with affected persons expressing varying degrees of joint laxity and other symptoms (Best Pract. Res. Clin. Rheumatol. 2003;17:989–1004). Women are affected approximately three times more commonly than men are.

Hyperextensibility of the finger joint is typical of hypermobility syndrome. A common misconception is that the diagnosis requires the involvement of four or more joints. In fact, only one joint need be hypermobile.

Excessive stretchiness of skin is associated with hypermobility syndrome. Paper-thin scars and stretch marks are other common cutaneous findings. Photos courtesy Dr. Rodney Grahame

GLASGOW, SCOTLAND — Joint hypermobility syndrome is profoundly underdiagnosed and its impact underestimated despite its being one of the most common causes of widespread chronic pain—and indeed may be the most common rheumatic disorder, Dr. Rodney Grahame said at the annual meeting of the British Society for Rheumatology (BSR).

“I looked at a series of 500 unselected new patients referred to the rheumatology clinic at Willesden Community Hospital in London between 2003 and 2005, evaluating them for their rheumatic complaints but also to see how many fit the JHS [joint hypermobility syndrome] phenotype. What I found exceeded my expectations by several orders of magnitude—overall, 45% of patients fulfilled the criteria,” Dr. Grahame said.

In contrast with his findings, “many of our rheumatology colleagues consider JHS to be rather trivial and relatively uncommon, and in a survey we did of all the BSR members, most said they diagnosed, on average, approximately 10 new cases each year, and half rated the impact on patients' lives as fairly minimal,” he said (Rheumatology [Oxford] 2001;40:559–62).

Extrapolating from those data would suggest that if most rheumatologists are diagnosing only 10 cases per year, they are identifying only 4.5% of cases. “That means that in England, 103,568 cases are missed annually, as are 593,930 cases in the United States. These are appalling statistics,” he said.

Evaluation of joint hypermobility traditionally is done using the Beighton scoring system, said Dr. Grahame, who was involved in the development of what are known as the revised Beighton criteria. The Beighton score identifies symptoms such as the ability to passively dorsiflex the fifth metacarpophalangeal joint to 90 degrees or more, to oppose the thumb to the volar aspect of the ipsilateral forearm, or to place the hands flat on the floor without bending the knees. This system is less than reliable in pauciarticular hypermobility, however, which is often the case in JHS. A common misconception is that hypermobility requires the involvement of four or more joints. In fact, only one joint need be hypermobile in JHS, he said.

Other typical presenting symptoms include acute or chronic pain and joint clicking. There may be a history of subluxations or dislocations, because the laxity of the ligaments leads to joint instability. Pain avoidance, typically beginning in childhood or adolescence, often leads to muscle deconditioning. Cutaneous findings include stretchability, paper-thin scars, and stretch marks. Ocular involvement can manifest with drooping eyelids and blue sclerae. Anxiety and other psychological disturbances such as phobias are common.

It has become increasingly clear that autonomic disturbances also play a significant role in the syndrome, according to Dr. Alan Hakim, another speaker at the meeting, who heads a hypermobility clinic at Whipps Cross University Hospital, London.

Three types of autonomic disturbances are predominant: syncopal, cardiorespiratory, and gastrointestinal. “It's phenomenal how many patients report presyncopal symptoms such as faintness and dizziness,” Dr. Hakim said. In one series of 48 patients with JHS, 78% were found to have orthostatic hypotension, postural orthostatic tachycardia syndrome, or orthostatic intolerance (Am. J. Med. 2003;115:33–40).

Cardiorespiratory findings include shortness of breath, while the gastrointestinal problems are similar to those seen in irritable bowel syndrome. Approximately 30% of patients report at least one autonomic disturbance, 20% have two, and 13%–14% report three autonomic disturbances, Dr. Hakim said.

Joint hypermobility syndrome is a genetically determined disorder of matrix proteins that is characterized by articular hyperextension, skin changes, marfanoid body habitus, and other manifestations such as hernias and varicose veins. It is considered benign, in that it does not significantly alter life expectancy, but affects quality of life and may be associated with frequent dislocations and early osteoarthritis and osteoporosis.

JHS manifests an autosomal dominant pattern of inheritance, with affected persons expressing varying degrees of joint laxity and other symptoms (Best Pract. Res. Clin. Rheumatol. 2003;17:989–1004). Women are affected approximately three times more commonly than men are.

Hyperextensibility of the finger joint is typical of hypermobility syndrome. A common misconception is that the diagnosis requires the involvement of four or more joints. In fact, only one joint need be hypermobile.

Excessive stretchiness of skin is associated with hypermobility syndrome. Paper-thin scars and stretch marks are other common cutaneous findings. Photos courtesy Dr. Rodney Grahame

GLASGOW, SCOTLAND — High rates of insulin resistance among patients with rheumatoid arthritis may help explain these patients' increased risk for cardiovascular disease, according to a poster presented by Dr. George D. Kitas at the annual meeting of the British Society for Rheumatology.

Evidence has been increasing that suggests involvement of chronic inflammation in atherosclerosis and coronary heart disease in both rheumatoid arthritis (RA) patients and the general population, but the precise disease processes are not fully understood, Dr. Kitas noted.

Insulin resistance is strongly associated with systemic inflammation. Insulin itself is an anti-inflammatory hormone, the actions of which include suppression of proinflammatory transcription factors and adhesion molecules. It also has antioxidant properties and, in a rat model, suppresses cytokines including interleukin-1β, IL-6, and tumor necrosis factor.

Conversely, hypernutrition and the insulin-resistant state are proinflammatory, noted Dr. Kitas of the department of rheumatology, Dudley Group of Hospitals and the University of Birmingham, both in England.

“Evidence for this arises from observations that treatment of type 2 diabetes reduces C-reactive protein and macrophage chemotactic protein-1,” he wrote. Moreover, diabetic ketoacidosis induces an inflammatory response that normalizes with insulin treatment.

To investigate the prevalence and clinical factors associated with insulin resistance, Dr. Kitas and his colleagues assessed 244 consecutive RA patients. A total of 70.5% were female, mean age was 61.6 years, and mean disease duration was 13.5 years.

Mean body mass index (BMI) was 27.5 kg/m

Rheumatoid factor (RF) was positive in 70.5% of patients. A total of 6.6% already had a diagnosis of diabetes, compared with 2% of the United Kingdom population.

Insulin resistance was determined on the homeostasis model assessment (HOMA) index and the quantitative insulin sensitivity check index (QUICKI).

Among patients who did not have an established diagnosis of diabetes, 37.3% and 38.2% had abnormal findings on HOMA and QUICKI, respectively.

Among these patients with insulin resistance, systolic blood pressure, triglyceride and uric acid levels, and body mass index were significantly higher than in those with normal insulin function. CRP and RF titers also were higher, while high-density lipoprotein level was lower.

Logistic regression analysis found that higher BMI, RF titer, and uric acid level were independent predictors of insulin resistance, according to Dr. Kitas. Steroid use did not correlate with insulin resistance.

The association of elevated RF titer and insulin resistance has not previously been described, he noted. “A possible explanation for this may be that RF acts as a surrogate marker for cumulative inflammation or damage, or it may reflect metabolic or genetic processes influencing insulin sensitivity among RA patients.”

According to Dr. Kitas, the study raises the following questions that require further investigation:

▸ Could improved disease control reduce insulin resistance?

▸ Would BMI reduction and increased exercise reduce insulin resistance?

▸ Do patients with RA and insulin resistance subsequently develop type 2 diabetes?

▸ What is the precise role of RF in insulin resistance?

▸ Will a reduction in insulin resistance ultimately reduce the cardiovascular disease risk in RA patients?

GLASGOW, SCOTLAND — High rates of insulin resistance among patients with rheumatoid arthritis may help explain these patients' increased risk for cardiovascular disease, according to a poster presented by Dr. George D. Kitas at the annual meeting of the British Society for Rheumatology.

Evidence has been increasing that suggests involvement of chronic inflammation in atherosclerosis and coronary heart disease in both rheumatoid arthritis (RA) patients and the general population, but the precise disease processes are not fully understood, Dr. Kitas noted.

Insulin resistance is strongly associated with systemic inflammation. Insulin itself is an anti-inflammatory hormone, the actions of which include suppression of proinflammatory transcription factors and adhesion molecules. It also has antioxidant properties and, in a rat model, suppresses cytokines including interleukin-1β, IL-6, and tumor necrosis factor.

Conversely, hypernutrition and the insulin-resistant state are proinflammatory, noted Dr. Kitas of the department of rheumatology, Dudley Group of Hospitals and the University of Birmingham, both in England.

“Evidence for this arises from observations that treatment of type 2 diabetes reduces C-reactive protein and macrophage chemotactic protein-1,” he wrote. Moreover, diabetic ketoacidosis induces an inflammatory response that normalizes with insulin treatment.

To investigate the prevalence and clinical factors associated with insulin resistance, Dr. Kitas and his colleagues assessed 244 consecutive RA patients. A total of 70.5% were female, mean age was 61.6 years, and mean disease duration was 13.5 years.

Mean body mass index (BMI) was 27.5 kg/m

Rheumatoid factor (RF) was positive in 70.5% of patients. A total of 6.6% already had a diagnosis of diabetes, compared with 2% of the United Kingdom population.

Insulin resistance was determined on the homeostasis model assessment (HOMA) index and the quantitative insulin sensitivity check index (QUICKI).

Among patients who did not have an established diagnosis of diabetes, 37.3% and 38.2% had abnormal findings on HOMA and QUICKI, respectively.

Among these patients with insulin resistance, systolic blood pressure, triglyceride and uric acid levels, and body mass index were significantly higher than in those with normal insulin function. CRP and RF titers also were higher, while high-density lipoprotein level was lower.

Logistic regression analysis found that higher BMI, RF titer, and uric acid level were independent predictors of insulin resistance, according to Dr. Kitas. Steroid use did not correlate with insulin resistance.

The association of elevated RF titer and insulin resistance has not previously been described, he noted. “A possible explanation for this may be that RF acts as a surrogate marker for cumulative inflammation or damage, or it may reflect metabolic or genetic processes influencing insulin sensitivity among RA patients.”

According to Dr. Kitas, the study raises the following questions that require further investigation:

▸ Could improved disease control reduce insulin resistance?

▸ Would BMI reduction and increased exercise reduce insulin resistance?

▸ Do patients with RA and insulin resistance subsequently develop type 2 diabetes?

▸ What is the precise role of RF in insulin resistance?

▸ Will a reduction in insulin resistance ultimately reduce the cardiovascular disease risk in RA patients?

GLASGOW, SCOTLAND — High rates of insulin resistance among patients with rheumatoid arthritis may help explain these patients' increased risk for cardiovascular disease, according to a poster presented by Dr. George D. Kitas at the annual meeting of the British Society for Rheumatology.

Evidence has been increasing that suggests involvement of chronic inflammation in atherosclerosis and coronary heart disease in both rheumatoid arthritis (RA) patients and the general population, but the precise disease processes are not fully understood, Dr. Kitas noted.

Insulin resistance is strongly associated with systemic inflammation. Insulin itself is an anti-inflammatory hormone, the actions of which include suppression of proinflammatory transcription factors and adhesion molecules. It also has antioxidant properties and, in a rat model, suppresses cytokines including interleukin-1β, IL-6, and tumor necrosis factor.

Conversely, hypernutrition and the insulin-resistant state are proinflammatory, noted Dr. Kitas of the department of rheumatology, Dudley Group of Hospitals and the University of Birmingham, both in England.

“Evidence for this arises from observations that treatment of type 2 diabetes reduces C-reactive protein and macrophage chemotactic protein-1,” he wrote. Moreover, diabetic ketoacidosis induces an inflammatory response that normalizes with insulin treatment.

To investigate the prevalence and clinical factors associated with insulin resistance, Dr. Kitas and his colleagues assessed 244 consecutive RA patients. A total of 70.5% were female, mean age was 61.6 years, and mean disease duration was 13.5 years.

Mean body mass index (BMI) was 27.5 kg/m

Rheumatoid factor (RF) was positive in 70.5% of patients. A total of 6.6% already had a diagnosis of diabetes, compared with 2% of the United Kingdom population.

Insulin resistance was determined on the homeostasis model assessment (HOMA) index and the quantitative insulin sensitivity check index (QUICKI).

Among patients who did not have an established diagnosis of diabetes, 37.3% and 38.2% had abnormal findings on HOMA and QUICKI, respectively.

Among these patients with insulin resistance, systolic blood pressure, triglyceride and uric acid levels, and body mass index were significantly higher than in those with normal insulin function. CRP and RF titers also were higher, while high-density lipoprotein level was lower.

Logistic regression analysis found that higher BMI, RF titer, and uric acid level were independent predictors of insulin resistance, according to Dr. Kitas. Steroid use did not correlate with insulin resistance.

The association of elevated RF titer and insulin resistance has not previously been described, he noted. “A possible explanation for this may be that RF acts as a surrogate marker for cumulative inflammation or damage, or it may reflect metabolic or genetic processes influencing insulin sensitivity among RA patients.”

According to Dr. Kitas, the study raises the following questions that require further investigation:

▸ Could improved disease control reduce insulin resistance?

▸ Would BMI reduction and increased exercise reduce insulin resistance?

▸ Do patients with RA and insulin resistance subsequently develop type 2 diabetes?

▸ What is the precise role of RF in insulin resistance?

▸ Will a reduction in insulin resistance ultimately reduce the cardiovascular disease risk in RA patients?

LAS VEGAS — The use of high-dose liposomal amphotericin B was no more effective than standard doses for the treatment of invasive aspergillosis in a large randomized study, and was associated with significantly more adverse effects.

Invasive fungal infections remain a significant cause of morbidity and mortality in seriously immunocompromised patients, such as those with hematologic malignancies. Conventional amphotericin B deoxycholate has long been used, but is limited in efficacy and has significant toxicity. Three lipid formulations of the drug now are available and they are more easily tolerated, Dr. Mark Bresnik said at a meeting on fungal infections sponsored by Imedex.

For one of these, liposomal amphotericin B, the standard dose in invasive fungal infections is 3 mg/kg per day. However, preclinical studies have suggested that efficacy may increase with higher doses, and preliminary human studies found no significant increase in adverse effects with doses of 10 mg/kg per day, he reported.

To test the hypothesis that higher doses of liposomal amphotericin B might improve outcomes, a prospective, double-blind study was done to compare dosages of 10 mg/kg and 3 mg/kg daily in 201 highly immunocompromised patients. After the first 2 weeks of therapy, all patients could remain on the standard 3-mg/kg dosage for as long as the investigators deemed appropriate. The trial was conducted at 46 sites in Europe and Australia.

In both groups, 93% of patients had hematologic malignancies, and in two-thirds, the disease was uncontrolled. More than 70% were neutropenic at baseline. All patients had proven or probable invasive aspergillosis, or infection with another filamentous fungus; 95% had invasive pulmonary aspergillosis.

A favorable overall response rate (complete plus partial responses) was seen in 50% and 46% of the standard- and high-dose groups, respectively. Survival at 12 weeks in the two groups was 72% and 59%, said Dr. Bresnik, director of medical affairs for Gilead Sciences, manufacturer of liposomal amphotericin B (Ambisome).

The two groups did not differ significantly in overall response rate or survival. These rates were comparable with those previously reported for voriconazole, a broad-spectrum triazole agent, vs. conventional amphotericin B (N. Engl. J. Med. 2002;347:408–15).

Median duration of treatment was 15 days in the standard-dose arm and 14 days in the high-dose arm; treatment duration for some patients in both arms extended upward of 5 weeks, he said.

No unusual or previously unrecognized safety issues were seen. Discontinuations due to toxicity were more frequent in the high-dose group, at 32%, vs. 20% in the standard-dose group. Nephrotoxicity and hypokalemia occurred more often in the high-dose group, at 31% and 30%, compared with 14% and 16%, respectively, in the low-dose group, Dr. Bresnik reported.

“So what the trial has told us is that the appropriate dose is 3 mg/kg per day, but 95% of patients in this trial had invasive pulmonary aspergillosis. What that means is that the data are not yet available to determine whether benefits could be obtained with higher doses in nonpulmonary sites of infection or with non-Aspergillus molds such as zygomycetes,” he said.

LAS VEGAS — The use of high-dose liposomal amphotericin B was no more effective than standard doses for the treatment of invasive aspergillosis in a large randomized study, and was associated with significantly more adverse effects.

Invasive fungal infections remain a significant cause of morbidity and mortality in seriously immunocompromised patients, such as those with hematologic malignancies. Conventional amphotericin B deoxycholate has long been used, but is limited in efficacy and has significant toxicity. Three lipid formulations of the drug now are available and they are more easily tolerated, Dr. Mark Bresnik said at a meeting on fungal infections sponsored by Imedex.

For one of these, liposomal amphotericin B, the standard dose in invasive fungal infections is 3 mg/kg per day. However, preclinical studies have suggested that efficacy may increase with higher doses, and preliminary human studies found no significant increase in adverse effects with doses of 10 mg/kg per day, he reported.

To test the hypothesis that higher doses of liposomal amphotericin B might improve outcomes, a prospective, double-blind study was done to compare dosages of 10 mg/kg and 3 mg/kg daily in 201 highly immunocompromised patients. After the first 2 weeks of therapy, all patients could remain on the standard 3-mg/kg dosage for as long as the investigators deemed appropriate. The trial was conducted at 46 sites in Europe and Australia.

In both groups, 93% of patients had hematologic malignancies, and in two-thirds, the disease was uncontrolled. More than 70% were neutropenic at baseline. All patients had proven or probable invasive aspergillosis, or infection with another filamentous fungus; 95% had invasive pulmonary aspergillosis.

A favorable overall response rate (complete plus partial responses) was seen in 50% and 46% of the standard- and high-dose groups, respectively. Survival at 12 weeks in the two groups was 72% and 59%, said Dr. Bresnik, director of medical affairs for Gilead Sciences, manufacturer of liposomal amphotericin B (Ambisome).

The two groups did not differ significantly in overall response rate or survival. These rates were comparable with those previously reported for voriconazole, a broad-spectrum triazole agent, vs. conventional amphotericin B (N. Engl. J. Med. 2002;347:408–15).

Median duration of treatment was 15 days in the standard-dose arm and 14 days in the high-dose arm; treatment duration for some patients in both arms extended upward of 5 weeks, he said.

No unusual or previously unrecognized safety issues were seen. Discontinuations due to toxicity were more frequent in the high-dose group, at 32%, vs. 20% in the standard-dose group. Nephrotoxicity and hypokalemia occurred more often in the high-dose group, at 31% and 30%, compared with 14% and 16%, respectively, in the low-dose group, Dr. Bresnik reported.

“So what the trial has told us is that the appropriate dose is 3 mg/kg per day, but 95% of patients in this trial had invasive pulmonary aspergillosis. What that means is that the data are not yet available to determine whether benefits could be obtained with higher doses in nonpulmonary sites of infection or with non-Aspergillus molds such as zygomycetes,” he said.

LAS VEGAS — The use of high-dose liposomal amphotericin B was no more effective than standard doses for the treatment of invasive aspergillosis in a large randomized study, and was associated with significantly more adverse effects.

Invasive fungal infections remain a significant cause of morbidity and mortality in seriously immunocompromised patients, such as those with hematologic malignancies. Conventional amphotericin B deoxycholate has long been used, but is limited in efficacy and has significant toxicity. Three lipid formulations of the drug now are available and they are more easily tolerated, Dr. Mark Bresnik said at a meeting on fungal infections sponsored by Imedex.

For one of these, liposomal amphotericin B, the standard dose in invasive fungal infections is 3 mg/kg per day. However, preclinical studies have suggested that efficacy may increase with higher doses, and preliminary human studies found no significant increase in adverse effects with doses of 10 mg/kg per day, he reported.

To test the hypothesis that higher doses of liposomal amphotericin B might improve outcomes, a prospective, double-blind study was done to compare dosages of 10 mg/kg and 3 mg/kg daily in 201 highly immunocompromised patients. After the first 2 weeks of therapy, all patients could remain on the standard 3-mg/kg dosage for as long as the investigators deemed appropriate. The trial was conducted at 46 sites in Europe and Australia.

In both groups, 93% of patients had hematologic malignancies, and in two-thirds, the disease was uncontrolled. More than 70% were neutropenic at baseline. All patients had proven or probable invasive aspergillosis, or infection with another filamentous fungus; 95% had invasive pulmonary aspergillosis.

A favorable overall response rate (complete plus partial responses) was seen in 50% and 46% of the standard- and high-dose groups, respectively. Survival at 12 weeks in the two groups was 72% and 59%, said Dr. Bresnik, director of medical affairs for Gilead Sciences, manufacturer of liposomal amphotericin B (Ambisome).

The two groups did not differ significantly in overall response rate or survival. These rates were comparable with those previously reported for voriconazole, a broad-spectrum triazole agent, vs. conventional amphotericin B (N. Engl. J. Med. 2002;347:408–15).

Median duration of treatment was 15 days in the standard-dose arm and 14 days in the high-dose arm; treatment duration for some patients in both arms extended upward of 5 weeks, he said.

No unusual or previously unrecognized safety issues were seen. Discontinuations due to toxicity were more frequent in the high-dose group, at 32%, vs. 20% in the standard-dose group. Nephrotoxicity and hypokalemia occurred more often in the high-dose group, at 31% and 30%, compared with 14% and 16%, respectively, in the low-dose group, Dr. Bresnik reported.

“So what the trial has told us is that the appropriate dose is 3 mg/kg per day, but 95% of patients in this trial had invasive pulmonary aspergillosis. What that means is that the data are not yet available to determine whether benefits could be obtained with higher doses in nonpulmonary sites of infection or with non-Aspergillus molds such as zygomycetes,” he said.

Diagnosis: Alternariosis

LONDON — Culture of a biopsy specimen revealed the presence of the ubiquitous fungus Alternaria alternata, and an indirect immunofluorescence assay found Alternaria antibodies in a titer of 1:640.

Histopathologic examination found a granulomatous infiltrate in the dermis, and a periodic acid-Schiff stain was positive for septated hyphomycetes.

Cutaneous alternariosis can result directly, via traumatic inoculation of the fungus into the skin, or secondarily after inhalation of the conidia and systemic spread to the dermis or epidermis, Dr. Mira Kadurina said at the 14th Congress of the European Academy of Dermatology and Venereology.

Histopathologic findings can include microabscesses or granulomatous formations in the dermis and subcutis.

Hyphal elements in the tissue may be branched, thick-walled filaments; spherical cells; or short chains of oblong cells, explained Dr. Kadurina, who is with the Military Medical Academy in Sofia, Bulgaria.

This patient was not immunocompromised, but most cases of alternariosis have been reported in patients with malignancies, endocrine or autoimmune disease, a history of organ transplantation, or immunosuppressive therapy. More than half of cases have been seen in patients undergoing systemic corticosteroid treatment, Dr. Kadurina said.

The patient received three 14-day courses of itraconazole, 400 mg/day, over a period of 3 months, and responded well clinically. The antibody titer decreased to 1:80. Hyperpigmented scarring remained, but pain and pruritus resolved and no new lesions subsequently appeared.

Granulomatous infiltrate was present in the dermis. Courtesy Dr. Mira Kadurina

Diagnosis: Alternariosis

LONDON — Culture of a biopsy specimen revealed the presence of the ubiquitous fungus Alternaria alternata, and an indirect immunofluorescence assay found Alternaria antibodies in a titer of 1:640.

Histopathologic examination found a granulomatous infiltrate in the dermis, and a periodic acid-Schiff stain was positive for septated hyphomycetes.

Cutaneous alternariosis can result directly, via traumatic inoculation of the fungus into the skin, or secondarily after inhalation of the conidia and systemic spread to the dermis or epidermis, Dr. Mira Kadurina said at the 14th Congress of the European Academy of Dermatology and Venereology.

Histopathologic findings can include microabscesses or granulomatous formations in the dermis and subcutis.

Hyphal elements in the tissue may be branched, thick-walled filaments; spherical cells; or short chains of oblong cells, explained Dr. Kadurina, who is with the Military Medical Academy in Sofia, Bulgaria.

This patient was not immunocompromised, but most cases of alternariosis have been reported in patients with malignancies, endocrine or autoimmune disease, a history of organ transplantation, or immunosuppressive therapy. More than half of cases have been seen in patients undergoing systemic corticosteroid treatment, Dr. Kadurina said.

The patient received three 14-day courses of itraconazole, 400 mg/day, over a period of 3 months, and responded well clinically. The antibody titer decreased to 1:80. Hyperpigmented scarring remained, but pain and pruritus resolved and no new lesions subsequently appeared.

Granulomatous infiltrate was present in the dermis. Courtesy Dr. Mira Kadurina

Diagnosis: Alternariosis

LONDON — Culture of a biopsy specimen revealed the presence of the ubiquitous fungus Alternaria alternata, and an indirect immunofluorescence assay found Alternaria antibodies in a titer of 1:640.

Histopathologic examination found a granulomatous infiltrate in the dermis, and a periodic acid-Schiff stain was positive for septated hyphomycetes.

Cutaneous alternariosis can result directly, via traumatic inoculation of the fungus into the skin, or secondarily after inhalation of the conidia and systemic spread to the dermis or epidermis, Dr. Mira Kadurina said at the 14th Congress of the European Academy of Dermatology and Venereology.

Histopathologic findings can include microabscesses or granulomatous formations in the dermis and subcutis.

Hyphal elements in the tissue may be branched, thick-walled filaments; spherical cells; or short chains of oblong cells, explained Dr. Kadurina, who is with the Military Medical Academy in Sofia, Bulgaria.

This patient was not immunocompromised, but most cases of alternariosis have been reported in patients with malignancies, endocrine or autoimmune disease, a history of organ transplantation, or immunosuppressive therapy. More than half of cases have been seen in patients undergoing systemic corticosteroid treatment, Dr. Kadurina said.

The patient received three 14-day courses of itraconazole, 400 mg/day, over a period of 3 months, and responded well clinically. The antibody titer decreased to 1:80. Hyperpigmented scarring remained, but pain and pruritus resolved and no new lesions subsequently appeared.

Granulomatous infiltrate was present in the dermis. Courtesy Dr. Mira Kadurina

LAS VEGAS — Results of two large studies have shown that prophylaxis with oral posaconazole can prevent invasive fungal infections in bone marrow transplant recipients and patients with hematologic malignancies, Dr. Catherine J. Hardalo reported.

Invasive fungal infections have emerged as a potentially lethal complication for immunosuppressed patients, and some of the pathogens involved are resistant to standard antifungal therapy. Posaconazole is a broad-spectrum agent with activity against Aspergillus, Fusarium, Coccidioides, Candida, pigmented and hyaline molds, and the Zygomycetes, she said at a meeting on fungal infections sponsored by Imedex.

Previously, the drug had been used primarily as salvage therapy for patients with invasive aspergillosis, with about 40% of patients responding, said Dr. Hardalo, senior director of anti-infectives clinical research, Schering-Plough Research Institute, Kenilworth, N.J.

Current prophylaxis options include fluconazole and micafungin for patients undergoing hematopoietic stem cell transplantation, and itraconazole (in Europe only) for the prevention of fungal infections during prolonged neutropenia.

Posaconazole now has been evaluated in a multicenter, double-blind study that included 600 patients who had undergone allogeneic stem cell transplantation and had graft-versus-host disease. They were randomized to receive either posaconazole 200 mg three times daily, or fluconazole 400 mg/day, for 16 weeks. The incidence of invasive fungal infections and invasive aspergillosis was 2% and 1%, respectively, in the posaconazole group vs. 8% and 6% in the fluconazole group.

A total of 76 patients in the posaconazole group died, as did 84 in the fluconazole group. This difference was not significant. However, only 4 patients on posaconazole died from fungal causes, which was significantly fewer than the 12 patients with fungal-related deaths in the fluconazole group.

In a second study, 600 patients with acute myelogenous leukemia or mylodysplastic syndrome received the same dose of posaconazole or fluconazole, 400 mg once a day, or itraconazole, 200 mg twice a day. The number of cases of invasive fungal infection and invasive aspergillosis were “virtually the same” as in the other study: 2% and 1% for posaconazole, and 8% and 7% for the other azoles, Dr. Hardalo said.

There were 49 deaths among patients receiving posaconazole and 67 among patients receiving the other azoles. Five deaths in the posaconazole group were fungal related, as were 16 in the other-azole groups. These differences were statistically significant.

Moreover, for the first time, a survival benefit was seen among neutropenic patients, she said.

LAS VEGAS — Results of two large studies have shown that prophylaxis with oral posaconazole can prevent invasive fungal infections in bone marrow transplant recipients and patients with hematologic malignancies, Dr. Catherine J. Hardalo reported.

Invasive fungal infections have emerged as a potentially lethal complication for immunosuppressed patients, and some of the pathogens involved are resistant to standard antifungal therapy. Posaconazole is a broad-spectrum agent with activity against Aspergillus, Fusarium, Coccidioides, Candida, pigmented and hyaline molds, and the Zygomycetes, she said at a meeting on fungal infections sponsored by Imedex.

Previously, the drug had been used primarily as salvage therapy for patients with invasive aspergillosis, with about 40% of patients responding, said Dr. Hardalo, senior director of anti-infectives clinical research, Schering-Plough Research Institute, Kenilworth, N.J.

Current prophylaxis options include fluconazole and micafungin for patients undergoing hematopoietic stem cell transplantation, and itraconazole (in Europe only) for the prevention of fungal infections during prolonged neutropenia.

Posaconazole now has been evaluated in a multicenter, double-blind study that included 600 patients who had undergone allogeneic stem cell transplantation and had graft-versus-host disease. They were randomized to receive either posaconazole 200 mg three times daily, or fluconazole 400 mg/day, for 16 weeks. The incidence of invasive fungal infections and invasive aspergillosis was 2% and 1%, respectively, in the posaconazole group vs. 8% and 6% in the fluconazole group.

A total of 76 patients in the posaconazole group died, as did 84 in the fluconazole group. This difference was not significant. However, only 4 patients on posaconazole died from fungal causes, which was significantly fewer than the 12 patients with fungal-related deaths in the fluconazole group.

In a second study, 600 patients with acute myelogenous leukemia or mylodysplastic syndrome received the same dose of posaconazole or fluconazole, 400 mg once a day, or itraconazole, 200 mg twice a day. The number of cases of invasive fungal infection and invasive aspergillosis were “virtually the same” as in the other study: 2% and 1% for posaconazole, and 8% and 7% for the other azoles, Dr. Hardalo said.

There were 49 deaths among patients receiving posaconazole and 67 among patients receiving the other azoles. Five deaths in the posaconazole group were fungal related, as were 16 in the other-azole groups. These differences were statistically significant.

Moreover, for the first time, a survival benefit was seen among neutropenic patients, she said.

LAS VEGAS — Results of two large studies have shown that prophylaxis with oral posaconazole can prevent invasive fungal infections in bone marrow transplant recipients and patients with hematologic malignancies, Dr. Catherine J. Hardalo reported.

Invasive fungal infections have emerged as a potentially lethal complication for immunosuppressed patients, and some of the pathogens involved are resistant to standard antifungal therapy. Posaconazole is a broad-spectrum agent with activity against Aspergillus, Fusarium, Coccidioides, Candida, pigmented and hyaline molds, and the Zygomycetes, she said at a meeting on fungal infections sponsored by Imedex.

Previously, the drug had been used primarily as salvage therapy for patients with invasive aspergillosis, with about 40% of patients responding, said Dr. Hardalo, senior director of anti-infectives clinical research, Schering-Plough Research Institute, Kenilworth, N.J.

Current prophylaxis options include fluconazole and micafungin for patients undergoing hematopoietic stem cell transplantation, and itraconazole (in Europe only) for the prevention of fungal infections during prolonged neutropenia.

Posaconazole now has been evaluated in a multicenter, double-blind study that included 600 patients who had undergone allogeneic stem cell transplantation and had graft-versus-host disease. They were randomized to receive either posaconazole 200 mg three times daily, or fluconazole 400 mg/day, for 16 weeks. The incidence of invasive fungal infections and invasive aspergillosis was 2% and 1%, respectively, in the posaconazole group vs. 8% and 6% in the fluconazole group.

A total of 76 patients in the posaconazole group died, as did 84 in the fluconazole group. This difference was not significant. However, only 4 patients on posaconazole died from fungal causes, which was significantly fewer than the 12 patients with fungal-related deaths in the fluconazole group.

In a second study, 600 patients with acute myelogenous leukemia or mylodysplastic syndrome received the same dose of posaconazole or fluconazole, 400 mg once a day, or itraconazole, 200 mg twice a day. The number of cases of invasive fungal infection and invasive aspergillosis were “virtually the same” as in the other study: 2% and 1% for posaconazole, and 8% and 7% for the other azoles, Dr. Hardalo said.

There were 49 deaths among patients receiving posaconazole and 67 among patients receiving the other azoles. Five deaths in the posaconazole group were fungal related, as were 16 in the other-azole groups. These differences were statistically significant.

Moreover, for the first time, a survival benefit was seen among neutropenic patients, she said.

LAS VEGAS — Dematiaceous, or darkly pigmented, fungi are emerging as an important cause of disease, and certain types of infections with these pathogens are associated with high rates of mortality, even among the immunocompetent, Dr. Sanjay G. Revankar said at a meeting on fungal infections sponsored by Imedex.

This is a heterogeneous group of fungi that includes more than 60 genera and 100 species found worldwide in soil and air. Melanin, present in the cell wall, provides the coloration of these pathogens and appears to be a virulence factor, providing protection from free radicals, hydrolytic enzymes, and ultraviolet damage.

One of the clinical syndromes associated with various species of dematiaceous fungi increasingly being seen is phaeohyphomycosis. Most of the species implicated are opportunists, but some may be true pathogens, said Dr. Revankar of the University of Texas Southwestern Medical Center, Dallas.

The diagnosis of phaeohyphomycosis requires expert interpretation of colony and microscopic morphology. The typical histologic findings include irregularly swollen hyphae and yeastlike forms. In contrast to many other fungi, there are no adequate serologic or antigen tests for the species that cause phaeohyphomycosis, he said.

The range of clinical syndromes comprising phaeohyphomycosis includes the following:

▸ Superficial infections. These typically manifest as subcutaneous nodules appearing after minor trauma to the skin and inoculation with species of Exophiala, Alternaria, or Phialophora. Successful treatment often requires only excision, although an azole is sometimes also given.

▸ Allergic disease. Most cases of sinusitis and bronchopulmonary mycosis are caused by species of Curvularia or Bipolaris. Sinusitis is characterized by the presence of allergic mucin and elevated IgE; treatment includes surgery plus corticosteroids. Bronchopulmonary mycosis is associated with elevated IgE or eosinophilia, and treatment relies on corticosteroids. Antifungal therapy is not routinely used for these infections, Dr. Revankar said.

▸ Pneumonia. This has been seen most in immunocompromised patients, and may be characterized by hemoptysis. Among the pathogens implicated are species of Exophiala and Chaetomium. Lipid amphotericin B is the preferred treatment for these seriously ill patients, followed by an azole if the patient stabilizes, but mortality is high, he said.

▸ CNS phaeohyphomycosis. This infection shows a 3:1 male predominance and has been reported worldwide. “What is really unusual is that more than half of patients seem to have no risk factors—no chemotherapy, HIV, or other immunodeficiency,” Dr. Revankar said. In a series of 101 patients with CNS infection, the classic triad seen with bacterial brain abscess—fever, headache, and neurologic deficits—was present in fewer than 5% of patients (Clin. Infect. Dis. 2004;38:206–16). Overall mortality was 72%.

Many species have been isolated in CNS infections, but in nearly half of cases Cladophialophora bantiana was implicated.

There was little evidence of efficacy for any particular antifungal regimen in these patients with CNS disease. A combination of amphotericin B, 5-fluorocytosine, and itraconazole was associated with improved survival, but only six patients in the series received this combination. Voriconazole and posaconazole have shown in vitro activity, but there is very little clinical experience with these agents for this indication, he said.

▸ Disseminated phaeohyphomycosis. “This has been seen increasingly during the past 10–15 years, probably reflecting the type of patients we are seeing, such as those who are immunocompromised from treatment for other diseases,” Dr. Revankar said. Prior cardiac surgery, particularly involving bioprosthetic valve replacements, also has been identified as a risk factor.

In a series of 72 patients, fever was present in only 76%. Skin lesions were seen in 33%, sepsis in 11%, and eosinophilia in 11% (Clin. Infect. Dis. 2002;34:467–76). Blood cultures were positive, most commonly revealing Scedosporium prolificans in more than half of patients. Most of the cases were in Spain and Australia.

Overall mortality was 79%. In the immunocompromised it was 84%, and in the immunocompetent it was 65%. S. prolificans is resistant to all available agents, and no single drug or combination of drugs was associated with improved outcome in this series. In two cases, however, the combination of an azole plus terbinafine was successful. “I wouldn't recommend this routinely, but if you have no other options it might be something to consider. Terbinafine is not considered a particularly useful systemic drug because of its pharmacokinetics, but in these cases there really is not much else left,” he said.

LAS VEGAS — Dematiaceous, or darkly pigmented, fungi are emerging as an important cause of disease, and certain types of infections with these pathogens are associated with high rates of mortality, even among the immunocompetent, Dr. Sanjay G. Revankar said at a meeting on fungal infections sponsored by Imedex.

This is a heterogeneous group of fungi that includes more than 60 genera and 100 species found worldwide in soil and air. Melanin, present in the cell wall, provides the coloration of these pathogens and appears to be a virulence factor, providing protection from free radicals, hydrolytic enzymes, and ultraviolet damage.

One of the clinical syndromes associated with various species of dematiaceous fungi increasingly being seen is phaeohyphomycosis. Most of the species implicated are opportunists, but some may be true pathogens, said Dr. Revankar of the University of Texas Southwestern Medical Center, Dallas.

The diagnosis of phaeohyphomycosis requires expert interpretation of colony and microscopic morphology. The typical histologic findings include irregularly swollen hyphae and yeastlike forms. In contrast to many other fungi, there are no adequate serologic or antigen tests for the species that cause phaeohyphomycosis, he said.

The range of clinical syndromes comprising phaeohyphomycosis includes the following:

▸ Superficial infections. These typically manifest as subcutaneous nodules appearing after minor trauma to the skin and inoculation with species of Exophiala, Alternaria, or Phialophora. Successful treatment often requires only excision, although an azole is sometimes also given.

▸ Allergic disease. Most cases of sinusitis and bronchopulmonary mycosis are caused by species of Curvularia or Bipolaris. Sinusitis is characterized by the presence of allergic mucin and elevated IgE; treatment includes surgery plus corticosteroids. Bronchopulmonary mycosis is associated with elevated IgE or eosinophilia, and treatment relies on corticosteroids. Antifungal therapy is not routinely used for these infections, Dr. Revankar said.

▸ Pneumonia. This has been seen most in immunocompromised patients, and may be characterized by hemoptysis. Among the pathogens implicated are species of Exophiala and Chaetomium. Lipid amphotericin B is the preferred treatment for these seriously ill patients, followed by an azole if the patient stabilizes, but mortality is high, he said.

▸ CNS phaeohyphomycosis. This infection shows a 3:1 male predominance and has been reported worldwide. “What is really unusual is that more than half of patients seem to have no risk factors—no chemotherapy, HIV, or other immunodeficiency,” Dr. Revankar said. In a series of 101 patients with CNS infection, the classic triad seen with bacterial brain abscess—fever, headache, and neurologic deficits—was present in fewer than 5% of patients (Clin. Infect. Dis. 2004;38:206–16). Overall mortality was 72%.

Many species have been isolated in CNS infections, but in nearly half of cases Cladophialophora bantiana was implicated.

There was little evidence of efficacy for any particular antifungal regimen in these patients with CNS disease. A combination of amphotericin B, 5-fluorocytosine, and itraconazole was associated with improved survival, but only six patients in the series received this combination. Voriconazole and posaconazole have shown in vitro activity, but there is very little clinical experience with these agents for this indication, he said.

▸ Disseminated phaeohyphomycosis. “This has been seen increasingly during the past 10–15 years, probably reflecting the type of patients we are seeing, such as those who are immunocompromised from treatment for other diseases,” Dr. Revankar said. Prior cardiac surgery, particularly involving bioprosthetic valve replacements, also has been identified as a risk factor.

In a series of 72 patients, fever was present in only 76%. Skin lesions were seen in 33%, sepsis in 11%, and eosinophilia in 11% (Clin. Infect. Dis. 2002;34:467–76). Blood cultures were positive, most commonly revealing Scedosporium prolificans in more than half of patients. Most of the cases were in Spain and Australia.

Overall mortality was 79%. In the immunocompromised it was 84%, and in the immunocompetent it was 65%. S. prolificans is resistant to all available agents, and no single drug or combination of drugs was associated with improved outcome in this series. In two cases, however, the combination of an azole plus terbinafine was successful. “I wouldn't recommend this routinely, but if you have no other options it might be something to consider. Terbinafine is not considered a particularly useful systemic drug because of its pharmacokinetics, but in these cases there really is not much else left,” he said.

LAS VEGAS — Dematiaceous, or darkly pigmented, fungi are emerging as an important cause of disease, and certain types of infections with these pathogens are associated with high rates of mortality, even among the immunocompetent, Dr. Sanjay G. Revankar said at a meeting on fungal infections sponsored by Imedex.

This is a heterogeneous group of fungi that includes more than 60 genera and 100 species found worldwide in soil and air. Melanin, present in the cell wall, provides the coloration of these pathogens and appears to be a virulence factor, providing protection from free radicals, hydrolytic enzymes, and ultraviolet damage.

One of the clinical syndromes associated with various species of dematiaceous fungi increasingly being seen is phaeohyphomycosis. Most of the species implicated are opportunists, but some may be true pathogens, said Dr. Revankar of the University of Texas Southwestern Medical Center, Dallas.

The diagnosis of phaeohyphomycosis requires expert interpretation of colony and microscopic morphology. The typical histologic findings include irregularly swollen hyphae and yeastlike forms. In contrast to many other fungi, there are no adequate serologic or antigen tests for the species that cause phaeohyphomycosis, he said.

The range of clinical syndromes comprising phaeohyphomycosis includes the following:

▸ Superficial infections. These typically manifest as subcutaneous nodules appearing after minor trauma to the skin and inoculation with species of Exophiala, Alternaria, or Phialophora. Successful treatment often requires only excision, although an azole is sometimes also given.

▸ Allergic disease. Most cases of sinusitis and bronchopulmonary mycosis are caused by species of Curvularia or Bipolaris. Sinusitis is characterized by the presence of allergic mucin and elevated IgE; treatment includes surgery plus corticosteroids. Bronchopulmonary mycosis is associated with elevated IgE or eosinophilia, and treatment relies on corticosteroids. Antifungal therapy is not routinely used for these infections, Dr. Revankar said.

▸ Pneumonia. This has been seen most in immunocompromised patients, and may be characterized by hemoptysis. Among the pathogens implicated are species of Exophiala and Chaetomium. Lipid amphotericin B is the preferred treatment for these seriously ill patients, followed by an azole if the patient stabilizes, but mortality is high, he said.

▸ CNS phaeohyphomycosis. This infection shows a 3:1 male predominance and has been reported worldwide. “What is really unusual is that more than half of patients seem to have no risk factors—no chemotherapy, HIV, or other immunodeficiency,” Dr. Revankar said. In a series of 101 patients with CNS infection, the classic triad seen with bacterial brain abscess—fever, headache, and neurologic deficits—was present in fewer than 5% of patients (Clin. Infect. Dis. 2004;38:206–16). Overall mortality was 72%.

Many species have been isolated in CNS infections, but in nearly half of cases Cladophialophora bantiana was implicated.

There was little evidence of efficacy for any particular antifungal regimen in these patients with CNS disease. A combination of amphotericin B, 5-fluorocytosine, and itraconazole was associated with improved survival, but only six patients in the series received this combination. Voriconazole and posaconazole have shown in vitro activity, but there is very little clinical experience with these agents for this indication, he said.

▸ Disseminated phaeohyphomycosis. “This has been seen increasingly during the past 10–15 years, probably reflecting the type of patients we are seeing, such as those who are immunocompromised from treatment for other diseases,” Dr. Revankar said. Prior cardiac surgery, particularly involving bioprosthetic valve replacements, also has been identified as a risk factor.

In a series of 72 patients, fever was present in only 76%. Skin lesions were seen in 33%, sepsis in 11%, and eosinophilia in 11% (Clin. Infect. Dis. 2002;34:467–76). Blood cultures were positive, most commonly revealing Scedosporium prolificans in more than half of patients. Most of the cases were in Spain and Australia.

Overall mortality was 79%. In the immunocompromised it was 84%, and in the immunocompetent it was 65%. S. prolificans is resistant to all available agents, and no single drug or combination of drugs was associated with improved outcome in this series. In two cases, however, the combination of an azole plus terbinafine was successful. “I wouldn't recommend this routinely, but if you have no other options it might be something to consider. Terbinafine is not considered a particularly useful systemic drug because of its pharmacokinetics, but in these cases there really is not much else left,” he said.