Nancy Walsh

ABANO TERME, ITALY — Intravenous methotrexate proved to be an effective steroid-sparing treatment for recalcitrant cutaneous lupus, Dr. Joerg Wenzel reported at a congress on skin, rheumatism, and autoimmunity.

Dr. Wenzel and his associates in the department of dermatology at the University of Bonn (Germany) retrospectively analyzed patients who underwent treatment with methotrexate and whose skin lesions had not responded to antimalarials, azathioprine, mycophenolate mofetil, or dapsone.

Initially, the drug was given intravenously to 43 patients in doses of 15–25 mg/week. The dose was titrated down to a final range of 7.5–15 mg/week in eight patients. The oral route in doses of 10–20 mg/week was substituted in seven patients because of lack of compliance.

Disease activity was rated using a cutaneous lupus activation index (CLAI) that provided a single score reflecting the degree of skin involvement, grade of inflammation, and clinical course. At baseline, the mean CLAI was 5.13; this decreased to 1.73, with clinical response being observed after 2–8 weeks, Dr. Wenzel said. This was a “highly significant” decline in disease activity, and all but one patient experienced improvement, he said.

The greatest improvement was seen among 16 patients with the subacute cutaneous subtype of lupus erythematosus. Among these patients, the mean CLAI fell from 5.5 to 1.2, he said. Seven patients (16%) discontinued treatment because of significant side effects, including elevations of liver enzymes and pancytopenia. These quickly resolved when treatment was discontinued.

In 15 patients, administration was switched to the subcutaneous route, using a methotrexate formulation. Efficacy was equivalent to that seen with intravenous administration, and side effects were similar. There were significant differences in adverse effects, however, with parenteral administration, compared with oral delivery, probably because of individual differences in gastrointestinal resorption.

“My personal view is that the subcutaneous route opens the door to patient self-administration,” Dr. Wenzel said.

One curious finding in the study was that patients who had extensive lymphocytopenia before treatment experienced a significant increase in lymphocyte counts. This finding following methotrexate administration was strange, he said, as methotrexate itself is an immunosuppressive drug that can cause pancytopenia.

“I believe methotrexate blocks the recruitment of circulating autoreactive, cytotoxic lymphocytes from the blood into the skin,” he said. This hypothesis is supported by recent findings in psoriasis, where methotrexate reduced the expression of the skin-homing molecule cutaneous lymphocyte-associated antigen (Exp. Dermatol. 2004;13:426–34).

ABANO TERME, ITALY — Intravenous methotrexate proved to be an effective steroid-sparing treatment for recalcitrant cutaneous lupus, Dr. Joerg Wenzel reported at a congress on skin, rheumatism, and autoimmunity.

Dr. Wenzel and his associates in the department of dermatology at the University of Bonn (Germany) retrospectively analyzed patients who underwent treatment with methotrexate and whose skin lesions had not responded to antimalarials, azathioprine, mycophenolate mofetil, or dapsone.

Initially, the drug was given intravenously to 43 patients in doses of 15–25 mg/week. The dose was titrated down to a final range of 7.5–15 mg/week in eight patients. The oral route in doses of 10–20 mg/week was substituted in seven patients because of lack of compliance.

Disease activity was rated using a cutaneous lupus activation index (CLAI) that provided a single score reflecting the degree of skin involvement, grade of inflammation, and clinical course. At baseline, the mean CLAI was 5.13; this decreased to 1.73, with clinical response being observed after 2–8 weeks, Dr. Wenzel said. This was a “highly significant” decline in disease activity, and all but one patient experienced improvement, he said.

The greatest improvement was seen among 16 patients with the subacute cutaneous subtype of lupus erythematosus. Among these patients, the mean CLAI fell from 5.5 to 1.2, he said. Seven patients (16%) discontinued treatment because of significant side effects, including elevations of liver enzymes and pancytopenia. These quickly resolved when treatment was discontinued.

In 15 patients, administration was switched to the subcutaneous route, using a methotrexate formulation. Efficacy was equivalent to that seen with intravenous administration, and side effects were similar. There were significant differences in adverse effects, however, with parenteral administration, compared with oral delivery, probably because of individual differences in gastrointestinal resorption.

“My personal view is that the subcutaneous route opens the door to patient self-administration,” Dr. Wenzel said.

One curious finding in the study was that patients who had extensive lymphocytopenia before treatment experienced a significant increase in lymphocyte counts. This finding following methotrexate administration was strange, he said, as methotrexate itself is an immunosuppressive drug that can cause pancytopenia.

“I believe methotrexate blocks the recruitment of circulating autoreactive, cytotoxic lymphocytes from the blood into the skin,” he said. This hypothesis is supported by recent findings in psoriasis, where methotrexate reduced the expression of the skin-homing molecule cutaneous lymphocyte-associated antigen (Exp. Dermatol. 2004;13:426–34).

ABANO TERME, ITALY — Intravenous methotrexate proved to be an effective steroid-sparing treatment for recalcitrant cutaneous lupus, Dr. Joerg Wenzel reported at a congress on skin, rheumatism, and autoimmunity.

Dr. Wenzel and his associates in the department of dermatology at the University of Bonn (Germany) retrospectively analyzed patients who underwent treatment with methotrexate and whose skin lesions had not responded to antimalarials, azathioprine, mycophenolate mofetil, or dapsone.

Initially, the drug was given intravenously to 43 patients in doses of 15–25 mg/week. The dose was titrated down to a final range of 7.5–15 mg/week in eight patients. The oral route in doses of 10–20 mg/week was substituted in seven patients because of lack of compliance.

Disease activity was rated using a cutaneous lupus activation index (CLAI) that provided a single score reflecting the degree of skin involvement, grade of inflammation, and clinical course. At baseline, the mean CLAI was 5.13; this decreased to 1.73, with clinical response being observed after 2–8 weeks, Dr. Wenzel said. This was a “highly significant” decline in disease activity, and all but one patient experienced improvement, he said.

The greatest improvement was seen among 16 patients with the subacute cutaneous subtype of lupus erythematosus. Among these patients, the mean CLAI fell from 5.5 to 1.2, he said. Seven patients (16%) discontinued treatment because of significant side effects, including elevations of liver enzymes and pancytopenia. These quickly resolved when treatment was discontinued.

In 15 patients, administration was switched to the subcutaneous route, using a methotrexate formulation. Efficacy was equivalent to that seen with intravenous administration, and side effects were similar. There were significant differences in adverse effects, however, with parenteral administration, compared with oral delivery, probably because of individual differences in gastrointestinal resorption.

“My personal view is that the subcutaneous route opens the door to patient self-administration,” Dr. Wenzel said.

One curious finding in the study was that patients who had extensive lymphocytopenia before treatment experienced a significant increase in lymphocyte counts. This finding following methotrexate administration was strange, he said, as methotrexate itself is an immunosuppressive drug that can cause pancytopenia.

“I believe methotrexate blocks the recruitment of circulating autoreactive, cytotoxic lymphocytes from the blood into the skin,” he said. This hypothesis is supported by recent findings in psoriasis, where methotrexate reduced the expression of the skin-homing molecule cutaneous lymphocyte-associated antigen (Exp. Dermatol. 2004;13:426–34).

NEW YORK — Evidence is mounting that implicates the Epstein-Barr virus as the trigger that sets off the autoantibody production central to the pathogenesis of systemic lupus erythematosus, according to Dr. John B. Harley.

It has long been assumed that an etiologic agent from the environment would be required to initiate the production of the antinuclear antibodies that begin to appear in lupus patients' sera long before clinical disease develops. An association of lupus with Epstein-Barr virus (EBV) was first noted more than 3 decades ago, but the technical means of proving a connection was lacking, and the idea was set aside.

The EBV hypothesis was resurrected during the 1990s, however. Because almost all adults are infected with the virus—a hindrance to finding an epidemiologic connection—Dr. Harley and his colleagues investigated a group of 117 children and adolescents with lupus. Among patients aged 4–19 years, an infection rate of approximately 70% would be expected, and indeed, that was what was found among 153 controls, he said.

Among the lupus patients, however, 99% had seroconverted against EBV. “This was an odds ratio of 50,” Dr. Harley said at a rheumatology meeting sponsored by New York University.

Certain characteristics of the virus itself also lend credence to its etiologic probability. It infects B cells—B-cell dysregulation is prominent in lupus—and EBV itself can cause B-cell activation and autoantibody production. Among the antibodies that have been identified in patients with EBV-related mononucleosis are those targeting the Sm autoantigen, which otherwise is considered specific for lupus.

Infection is lifelong, providing continuous immune stimulation, and curiously, the virus also generates proteins that inhibit its own immune-mediated destruction, Dr. Harley said.

But in lupus, it is the host response to the virus that is the crucial aberrant factor, rather than the virus itself, said Dr. Harley, professor of immunology and medicine, University of Oklahoma Health Sciences Center, Oklahoma City. An alteration in humoral response to Epstein-Barr nuclear antigen 1 (EBNA-1) appears to be involved, and in describing his findings in the pediatric lupus cohort, Dr. Harley explained the altered response: “In the present study, lupus patients were shown to make higher concentrations of antibody against the fragments encompassing the amino and carboxyl ends of EBNA-1, while normal EBV-positive controls actually made higher levels of antibody against the middle fragment than did lupus patients” (Arthritis Rheum. 2006;54:360–8).

Further evidence has come from molecular techniques including epitope mapping and peptide sequencing. The first anti-Sm autoantibodies that appear in lupus patients' sera bind to a structure known as PPPGMRPP that cross-reacts with a similar peptide, PPPGRRP, on EBNA-1, Dr. Harley explained. A similar capability has been identified with anti-Ro antibodies, and the generation of cross-reacting antibodies to Sm or Ro may be the “central and critical step that defines the onset of lupus-specific autoimmunity,” he said. This critical step involving cross-reactive antibodies is then followed by epitope spreading and, ultimately, clinical disease.

Moreover, proof of the principle that a viral structure could generate autoimmunity was demonstrated by immunization of rabbits with the PPPGMRPP peptide. Following immunization, the animals went on to develop proteinuria, thrombocytopenia, elevated antinuclear antibody titers, and anti-double-stranded DNA antibodies (Nat. Med. 2005;11:85–9).

“We were able to provoke in an animal clinical findings that would satisfy the ACR criteria for lupus,” he said.

Of course much remains to be understood about the subsequent sequence of pathogenic events in lupus, as well as the role of genetics in predisposing patients to autoimmunity.

Dr. Harley's group also is focusing on the genetics of autoimmunity, and the Arthritis and Immunology Research Program, which he heads, at the Oklahoma Medical Research Foundation in Oklahoma City maintains a registry and repository of multiplex lupus families that is available for academic work. The registry can be accessed at http://lupus.omrf.org

NEW YORK — Evidence is mounting that implicates the Epstein-Barr virus as the trigger that sets off the autoantibody production central to the pathogenesis of systemic lupus erythematosus, according to Dr. John B. Harley.

It has long been assumed that an etiologic agent from the environment would be required to initiate the production of the antinuclear antibodies that begin to appear in lupus patients' sera long before clinical disease develops. An association of lupus with Epstein-Barr virus (EBV) was first noted more than 3 decades ago, but the technical means of proving a connection was lacking, and the idea was set aside.

The EBV hypothesis was resurrected during the 1990s, however. Because almost all adults are infected with the virus—a hindrance to finding an epidemiologic connection—Dr. Harley and his colleagues investigated a group of 117 children and adolescents with lupus. Among patients aged 4–19 years, an infection rate of approximately 70% would be expected, and indeed, that was what was found among 153 controls, he said.

Among the lupus patients, however, 99% had seroconverted against EBV. “This was an odds ratio of 50,” Dr. Harley said at a rheumatology meeting sponsored by New York University.

Certain characteristics of the virus itself also lend credence to its etiologic probability. It infects B cells—B-cell dysregulation is prominent in lupus—and EBV itself can cause B-cell activation and autoantibody production. Among the antibodies that have been identified in patients with EBV-related mononucleosis are those targeting the Sm autoantigen, which otherwise is considered specific for lupus.

Infection is lifelong, providing continuous immune stimulation, and curiously, the virus also generates proteins that inhibit its own immune-mediated destruction, Dr. Harley said.

But in lupus, it is the host response to the virus that is the crucial aberrant factor, rather than the virus itself, said Dr. Harley, professor of immunology and medicine, University of Oklahoma Health Sciences Center, Oklahoma City. An alteration in humoral response to Epstein-Barr nuclear antigen 1 (EBNA-1) appears to be involved, and in describing his findings in the pediatric lupus cohort, Dr. Harley explained the altered response: “In the present study, lupus patients were shown to make higher concentrations of antibody against the fragments encompassing the amino and carboxyl ends of EBNA-1, while normal EBV-positive controls actually made higher levels of antibody against the middle fragment than did lupus patients” (Arthritis Rheum. 2006;54:360–8).

Further evidence has come from molecular techniques including epitope mapping and peptide sequencing. The first anti-Sm autoantibodies that appear in lupus patients' sera bind to a structure known as PPPGMRPP that cross-reacts with a similar peptide, PPPGRRP, on EBNA-1, Dr. Harley explained. A similar capability has been identified with anti-Ro antibodies, and the generation of cross-reacting antibodies to Sm or Ro may be the “central and critical step that defines the onset of lupus-specific autoimmunity,” he said. This critical step involving cross-reactive antibodies is then followed by epitope spreading and, ultimately, clinical disease.

Moreover, proof of the principle that a viral structure could generate autoimmunity was demonstrated by immunization of rabbits with the PPPGMRPP peptide. Following immunization, the animals went on to develop proteinuria, thrombocytopenia, elevated antinuclear antibody titers, and anti-double-stranded DNA antibodies (Nat. Med. 2005;11:85–9).

“We were able to provoke in an animal clinical findings that would satisfy the ACR criteria for lupus,” he said.

Of course much remains to be understood about the subsequent sequence of pathogenic events in lupus, as well as the role of genetics in predisposing patients to autoimmunity.

Dr. Harley's group also is focusing on the genetics of autoimmunity, and the Arthritis and Immunology Research Program, which he heads, at the Oklahoma Medical Research Foundation in Oklahoma City maintains a registry and repository of multiplex lupus families that is available for academic work. The registry can be accessed at http://lupus.omrf.org

NEW YORK — Evidence is mounting that implicates the Epstein-Barr virus as the trigger that sets off the autoantibody production central to the pathogenesis of systemic lupus erythematosus, according to Dr. John B. Harley.

It has long been assumed that an etiologic agent from the environment would be required to initiate the production of the antinuclear antibodies that begin to appear in lupus patients' sera long before clinical disease develops. An association of lupus with Epstein-Barr virus (EBV) was first noted more than 3 decades ago, but the technical means of proving a connection was lacking, and the idea was set aside.

The EBV hypothesis was resurrected during the 1990s, however. Because almost all adults are infected with the virus—a hindrance to finding an epidemiologic connection—Dr. Harley and his colleagues investigated a group of 117 children and adolescents with lupus. Among patients aged 4–19 years, an infection rate of approximately 70% would be expected, and indeed, that was what was found among 153 controls, he said.

Among the lupus patients, however, 99% had seroconverted against EBV. “This was an odds ratio of 50,” Dr. Harley said at a rheumatology meeting sponsored by New York University.

Certain characteristics of the virus itself also lend credence to its etiologic probability. It infects B cells—B-cell dysregulation is prominent in lupus—and EBV itself can cause B-cell activation and autoantibody production. Among the antibodies that have been identified in patients with EBV-related mononucleosis are those targeting the Sm autoantigen, which otherwise is considered specific for lupus.

Infection is lifelong, providing continuous immune stimulation, and curiously, the virus also generates proteins that inhibit its own immune-mediated destruction, Dr. Harley said.

But in lupus, it is the host response to the virus that is the crucial aberrant factor, rather than the virus itself, said Dr. Harley, professor of immunology and medicine, University of Oklahoma Health Sciences Center, Oklahoma City. An alteration in humoral response to Epstein-Barr nuclear antigen 1 (EBNA-1) appears to be involved, and in describing his findings in the pediatric lupus cohort, Dr. Harley explained the altered response: “In the present study, lupus patients were shown to make higher concentrations of antibody against the fragments encompassing the amino and carboxyl ends of EBNA-1, while normal EBV-positive controls actually made higher levels of antibody against the middle fragment than did lupus patients” (Arthritis Rheum. 2006;54:360–8).

Further evidence has come from molecular techniques including epitope mapping and peptide sequencing. The first anti-Sm autoantibodies that appear in lupus patients' sera bind to a structure known as PPPGMRPP that cross-reacts with a similar peptide, PPPGRRP, on EBNA-1, Dr. Harley explained. A similar capability has been identified with anti-Ro antibodies, and the generation of cross-reacting antibodies to Sm or Ro may be the “central and critical step that defines the onset of lupus-specific autoimmunity,” he said. This critical step involving cross-reactive antibodies is then followed by epitope spreading and, ultimately, clinical disease.

Moreover, proof of the principle that a viral structure could generate autoimmunity was demonstrated by immunization of rabbits with the PPPGMRPP peptide. Following immunization, the animals went on to develop proteinuria, thrombocytopenia, elevated antinuclear antibody titers, and anti-double-stranded DNA antibodies (Nat. Med. 2005;11:85–9).

“We were able to provoke in an animal clinical findings that would satisfy the ACR criteria for lupus,” he said.

Of course much remains to be understood about the subsequent sequence of pathogenic events in lupus, as well as the role of genetics in predisposing patients to autoimmunity.

Dr. Harley's group also is focusing on the genetics of autoimmunity, and the Arthritis and Immunology Research Program, which he heads, at the Oklahoma Medical Research Foundation in Oklahoma City maintains a registry and repository of multiplex lupus families that is available for academic work. The registry can be accessed at http://lupus.omrf.org

MIAMI BEACH — Consider whether antimicrobial prophylaxis is needed for cosmetic procedures by evaluating the nature and extent of any wound that may result, as well as the patient's history of herpes simplex infection, Dr. Mark S. Nestor said at a symposium sponsored by the Florida Society of Dermatology and Dermatologic Surgery.

Prophylaxis is a must for ablative procedures such as CO₂ and erbium laser resurfacing, but clinical judgment is needed for other procedures. More aggressive nonablative procedures such as Fraxel laser treatment can cause superficial wounds that last 2–7 days; judicious use of antibiotics may be indicated, he said.

For photodynamic therapy and Thermage, antibiotic prophylaxis is generally not needed unless the patient has risk factors such as diabetes or immune suppression or is malnourished, he said.

The antibiotic used for prophylaxis should be sufficiently broad spectrum to cover not only gram-positive streptococcal and staphylococcal infections, but also the important gram-negative pathogens. A useful choice is cefdinir (Omnicef), which has excellent skin penetration and can be used even in penicillin-allergic patients, he said.

"You are going to get calls from the pharmacist about using a cephalosporin in penicillin-allergic patients, but there is no problem with this whatsoever," he said. The reason for this lies in the structure of the drug: Cefdinir's side chains are different from those of penicillin or ampicillin.

Antiviral prophylaxis should be considered for susceptible patients. "For patients who get frequent cold sores, there really is no reason not to give these drugs because they are safe and easily tolerated," he said. Either famciclovir or valacyclovir can be used.

Prophylaxis is not required with the use of injectable fillers, but antiviral treatment may be needed if the lips are the site of injection and the trauma results in reactivation, said Dr. Nestor, who is in private practice in Aventura, Fla.

Antiviral prophylaxis can begin 2 days before the procedure, while antibiotic prophylaxis should begin the night before or the morning of the procedure. Both should continue for about 10 days, until the patient is fully reepithelialized, he said.

Prophylaxis can prevent many, but not all, infections. Early signs of bacterial infection include increasing redness, pain, and new formation of ulcerations. Cultures and a change of antibiotic are often necessary, and vigilance is needed because scarring can occur, he said.

If a viral infection occurs while the patient is on an antiviral drug, the dosage can be increased. "If the patient is on 250 mg of famciclovir twice a day, I will double it or even give 500 mg three times a day," he said.

Certain patients Dr. Nestor has seen over the years have experienced what he refers to as a nonhealing syndrome. They initially have an infection, but it is followed by an autoimmune phenomenon that prevents the wound from healing. "If you culture them, you will grow out everything. They can be treated with everything in the book but don't get better," he said. The approach he has used is to give them a judicious course of antibiotic treatment along with a short course of betamethasone dipropionate ointment. "We have had some amazing results because this cuts down the autoimmune response," he said.

Dr. Nestor disclosed that he is a member of the speakers' bureau for Abbott Laboratories, manufacturer of cefdinir.

Prophylaxis should continue for about 10 days, until the patient is fully reepithelialized. DR. NESTOR

MIAMI BEACH — Consider whether antimicrobial prophylaxis is needed for cosmetic procedures by evaluating the nature and extent of any wound that may result, as well as the patient's history of herpes simplex infection, Dr. Mark S. Nestor said at a symposium sponsored by the Florida Society of Dermatology and Dermatologic Surgery.

Prophylaxis is a must for ablative procedures such as CO₂ and erbium laser resurfacing, but clinical judgment is needed for other procedures. More aggressive nonablative procedures such as Fraxel laser treatment can cause superficial wounds that last 2–7 days; judicious use of antibiotics may be indicated, he said.

For photodynamic therapy and Thermage, antibiotic prophylaxis is generally not needed unless the patient has risk factors such as diabetes or immune suppression or is malnourished, he said.

The antibiotic used for prophylaxis should be sufficiently broad spectrum to cover not only gram-positive streptococcal and staphylococcal infections, but also the important gram-negative pathogens. A useful choice is cefdinir (Omnicef), which has excellent skin penetration and can be used even in penicillin-allergic patients, he said.

"You are going to get calls from the pharmacist about using a cephalosporin in penicillin-allergic patients, but there is no problem with this whatsoever," he said. The reason for this lies in the structure of the drug: Cefdinir's side chains are different from those of penicillin or ampicillin.

Antiviral prophylaxis should be considered for susceptible patients. "For patients who get frequent cold sores, there really is no reason not to give these drugs because they are safe and easily tolerated," he said. Either famciclovir or valacyclovir can be used.

Prophylaxis is not required with the use of injectable fillers, but antiviral treatment may be needed if the lips are the site of injection and the trauma results in reactivation, said Dr. Nestor, who is in private practice in Aventura, Fla.

Antiviral prophylaxis can begin 2 days before the procedure, while antibiotic prophylaxis should begin the night before or the morning of the procedure. Both should continue for about 10 days, until the patient is fully reepithelialized, he said.

Prophylaxis can prevent many, but not all, infections. Early signs of bacterial infection include increasing redness, pain, and new formation of ulcerations. Cultures and a change of antibiotic are often necessary, and vigilance is needed because scarring can occur, he said.

If a viral infection occurs while the patient is on an antiviral drug, the dosage can be increased. "If the patient is on 250 mg of famciclovir twice a day, I will double it or even give 500 mg three times a day," he said.

Certain patients Dr. Nestor has seen over the years have experienced what he refers to as a nonhealing syndrome. They initially have an infection, but it is followed by an autoimmune phenomenon that prevents the wound from healing. "If you culture them, you will grow out everything. They can be treated with everything in the book but don't get better," he said. The approach he has used is to give them a judicious course of antibiotic treatment along with a short course of betamethasone dipropionate ointment. "We have had some amazing results because this cuts down the autoimmune response," he said.

Dr. Nestor disclosed that he is a member of the speakers' bureau for Abbott Laboratories, manufacturer of cefdinir.

Prophylaxis should continue for about 10 days, until the patient is fully reepithelialized. DR. NESTOR

MIAMI BEACH — Consider whether antimicrobial prophylaxis is needed for cosmetic procedures by evaluating the nature and extent of any wound that may result, as well as the patient's history of herpes simplex infection, Dr. Mark S. Nestor said at a symposium sponsored by the Florida Society of Dermatology and Dermatologic Surgery.

Prophylaxis is a must for ablative procedures such as CO₂ and erbium laser resurfacing, but clinical judgment is needed for other procedures. More aggressive nonablative procedures such as Fraxel laser treatment can cause superficial wounds that last 2–7 days; judicious use of antibiotics may be indicated, he said.

For photodynamic therapy and Thermage, antibiotic prophylaxis is generally not needed unless the patient has risk factors such as diabetes or immune suppression or is malnourished, he said.

The antibiotic used for prophylaxis should be sufficiently broad spectrum to cover not only gram-positive streptococcal and staphylococcal infections, but also the important gram-negative pathogens. A useful choice is cefdinir (Omnicef), which has excellent skin penetration and can be used even in penicillin-allergic patients, he said.

"You are going to get calls from the pharmacist about using a cephalosporin in penicillin-allergic patients, but there is no problem with this whatsoever," he said. The reason for this lies in the structure of the drug: Cefdinir's side chains are different from those of penicillin or ampicillin.

Antiviral prophylaxis should be considered for susceptible patients. "For patients who get frequent cold sores, there really is no reason not to give these drugs because they are safe and easily tolerated," he said. Either famciclovir or valacyclovir can be used.

Prophylaxis is not required with the use of injectable fillers, but antiviral treatment may be needed if the lips are the site of injection and the trauma results in reactivation, said Dr. Nestor, who is in private practice in Aventura, Fla.

Antiviral prophylaxis can begin 2 days before the procedure, while antibiotic prophylaxis should begin the night before or the morning of the procedure. Both should continue for about 10 days, until the patient is fully reepithelialized, he said.

Prophylaxis can prevent many, but not all, infections. Early signs of bacterial infection include increasing redness, pain, and new formation of ulcerations. Cultures and a change of antibiotic are often necessary, and vigilance is needed because scarring can occur, he said.

If a viral infection occurs while the patient is on an antiviral drug, the dosage can be increased. "If the patient is on 250 mg of famciclovir twice a day, I will double it or even give 500 mg three times a day," he said.

Certain patients Dr. Nestor has seen over the years have experienced what he refers to as a nonhealing syndrome. They initially have an infection, but it is followed by an autoimmune phenomenon that prevents the wound from healing. "If you culture them, you will grow out everything. They can be treated with everything in the book but don't get better," he said. The approach he has used is to give them a judicious course of antibiotic treatment along with a short course of betamethasone dipropionate ointment. "We have had some amazing results because this cuts down the autoimmune response," he said.

Dr. Nestor disclosed that he is a member of the speakers' bureau for Abbott Laboratories, manufacturer of cefdinir.

Prophylaxis should continue for about 10 days, until the patient is fully reepithelialized. DR. NESTOR

ABANO TERME, ITALY — Much has been learned about triggering factors and the range of clinical manifestations in catastrophic antiphospholipid syndrome to describe a constellation of events including multiple organ failure, thrombotic microangiopathy, and tissue necrosis, but the pathogenesis is unclear and mortality remains in excess of 50%, said Dr. Ronald A. Asherson.

The condition, also known eponymously as Asherson's syndrome, is a rapidly progressive variant of the classic antiphospholipid syndrome, differing from the classic syndrome in exhibiting predominantly small-vessel involvement and occlusions of unusual organs such as the bowel, reproductive organs, and adrenals. A catastrophic antiphospholipid syndrome (CAPS) registry established by the European Forum on Antiphospholipid Antibodies now includes nearly 300 cases, said Dr. Asherson, who coined the term CAPS 14 years ago.

In a congress on skin, rheumatism, and autoimmunity, Dr. Asherson recalled the first patient in whom the syndrome was identified. “We had a patient who had disseminated intravascular coagulation, antiphospholipid antibodies, and who developed ischemic necrosis of the extremities following the ingestion of two tablets of hydrochlorothiazide,” he said. “This is a sulfa-containing drug, and we now know that sulfa drugs are dangerous for patients with lupus and the antiphospholipid syndrome,” he said.

Analysis of the patients enrolled in the registry has shown that in 60% of cases a trigger such as this can be identified. The most common is infection, which was reported in 22% of patients and included viral infections, leg ulcers, upper respiratory tract illnesses, and urinary tract infections. There also have been cases associated with typhoid fever, dengue, and malaria, he said.

It also has been reported that three patients developed CAPS following immunizations for yellow fever, Japanese B encephalomyelitis, and influenza, implicating peptides in vaccines as triggers.

Trauma associated with surgery is another common trigger, and was reported in 14% of patients in the registry. This can range from major abdominal surgery to something as minor as a needlestick or biopsy, said Dr. Asherson of the rheumatic disease unit, University of Cape Town, and the Rosebank Clinic, both in Johannesburg, South Africa.

The mechanism by which trauma might initiate CAPS remains uncertain, but may involve cytokine production affecting endothelial cell function and the upregulation of procoagulant molecules (Immunobiology 2005;210:727–33). Complement activation also is thought to contribute to the development of tissue injury in CAPS (Clin. Exp. Rheumatol. 2006; 24:S46–51).

Among patients in the registry, 84.5% have a past history of antiphospholipid syndrome, either primary or secondary to lupus or another connective tissue disease. All have been found to be positive for antiphospholipid antibodies, and 82% are positive for IgG anticardiolipin antibodies.

Clinical manifestations of CAPS among patients in the registry vary widely. Renal involvement has been seen in 73% of patients, pulmonary involvement has been observed in 68%, cerebral involvement in 63%, and cutaneous involvement in 58%. The pulmonary manifestations are both thrombotic and nonthrombotic and can include the adult respiratory distress syndrome and pulmonary hemorrhage.

Among patients who died and for whom necropsy findings are available, the major causes of death were cerebral, cardiac events, and infections. Microthromboses were present in 84.5%, Dr. Asherson said.

The registry is based at the systemic autoimmune diseases unit of the Hospital Clinic in Barcelona and is available at www.med.ub.es/MIMMUN/FORUM/CAPS.HTM

ABANO TERME, ITALY — Much has been learned about triggering factors and the range of clinical manifestations in catastrophic antiphospholipid syndrome to describe a constellation of events including multiple organ failure, thrombotic microangiopathy, and tissue necrosis, but the pathogenesis is unclear and mortality remains in excess of 50%, said Dr. Ronald A. Asherson.

The condition, also known eponymously as Asherson's syndrome, is a rapidly progressive variant of the classic antiphospholipid syndrome, differing from the classic syndrome in exhibiting predominantly small-vessel involvement and occlusions of unusual organs such as the bowel, reproductive organs, and adrenals. A catastrophic antiphospholipid syndrome (CAPS) registry established by the European Forum on Antiphospholipid Antibodies now includes nearly 300 cases, said Dr. Asherson, who coined the term CAPS 14 years ago.

In a congress on skin, rheumatism, and autoimmunity, Dr. Asherson recalled the first patient in whom the syndrome was identified. “We had a patient who had disseminated intravascular coagulation, antiphospholipid antibodies, and who developed ischemic necrosis of the extremities following the ingestion of two tablets of hydrochlorothiazide,” he said. “This is a sulfa-containing drug, and we now know that sulfa drugs are dangerous for patients with lupus and the antiphospholipid syndrome,” he said.

Analysis of the patients enrolled in the registry has shown that in 60% of cases a trigger such as this can be identified. The most common is infection, which was reported in 22% of patients and included viral infections, leg ulcers, upper respiratory tract illnesses, and urinary tract infections. There also have been cases associated with typhoid fever, dengue, and malaria, he said.

It also has been reported that three patients developed CAPS following immunizations for yellow fever, Japanese B encephalomyelitis, and influenza, implicating peptides in vaccines as triggers.

Trauma associated with surgery is another common trigger, and was reported in 14% of patients in the registry. This can range from major abdominal surgery to something as minor as a needlestick or biopsy, said Dr. Asherson of the rheumatic disease unit, University of Cape Town, and the Rosebank Clinic, both in Johannesburg, South Africa.

The mechanism by which trauma might initiate CAPS remains uncertain, but may involve cytokine production affecting endothelial cell function and the upregulation of procoagulant molecules (Immunobiology 2005;210:727–33). Complement activation also is thought to contribute to the development of tissue injury in CAPS (Clin. Exp. Rheumatol. 2006; 24:S46–51).

Among patients in the registry, 84.5% have a past history of antiphospholipid syndrome, either primary or secondary to lupus or another connective tissue disease. All have been found to be positive for antiphospholipid antibodies, and 82% are positive for IgG anticardiolipin antibodies.

Clinical manifestations of CAPS among patients in the registry vary widely. Renal involvement has been seen in 73% of patients, pulmonary involvement has been observed in 68%, cerebral involvement in 63%, and cutaneous involvement in 58%. The pulmonary manifestations are both thrombotic and nonthrombotic and can include the adult respiratory distress syndrome and pulmonary hemorrhage.

Among patients who died and for whom necropsy findings are available, the major causes of death were cerebral, cardiac events, and infections. Microthromboses were present in 84.5%, Dr. Asherson said.

The registry is based at the systemic autoimmune diseases unit of the Hospital Clinic in Barcelona and is available at www.med.ub.es/MIMMUN/FORUM/CAPS.HTM

ABANO TERME, ITALY — Much has been learned about triggering factors and the range of clinical manifestations in catastrophic antiphospholipid syndrome to describe a constellation of events including multiple organ failure, thrombotic microangiopathy, and tissue necrosis, but the pathogenesis is unclear and mortality remains in excess of 50%, said Dr. Ronald A. Asherson.

The condition, also known eponymously as Asherson's syndrome, is a rapidly progressive variant of the classic antiphospholipid syndrome, differing from the classic syndrome in exhibiting predominantly small-vessel involvement and occlusions of unusual organs such as the bowel, reproductive organs, and adrenals. A catastrophic antiphospholipid syndrome (CAPS) registry established by the European Forum on Antiphospholipid Antibodies now includes nearly 300 cases, said Dr. Asherson, who coined the term CAPS 14 years ago.

In a congress on skin, rheumatism, and autoimmunity, Dr. Asherson recalled the first patient in whom the syndrome was identified. “We had a patient who had disseminated intravascular coagulation, antiphospholipid antibodies, and who developed ischemic necrosis of the extremities following the ingestion of two tablets of hydrochlorothiazide,” he said. “This is a sulfa-containing drug, and we now know that sulfa drugs are dangerous for patients with lupus and the antiphospholipid syndrome,” he said.

Analysis of the patients enrolled in the registry has shown that in 60% of cases a trigger such as this can be identified. The most common is infection, which was reported in 22% of patients and included viral infections, leg ulcers, upper respiratory tract illnesses, and urinary tract infections. There also have been cases associated with typhoid fever, dengue, and malaria, he said.

It also has been reported that three patients developed CAPS following immunizations for yellow fever, Japanese B encephalomyelitis, and influenza, implicating peptides in vaccines as triggers.

Trauma associated with surgery is another common trigger, and was reported in 14% of patients in the registry. This can range from major abdominal surgery to something as minor as a needlestick or biopsy, said Dr. Asherson of the rheumatic disease unit, University of Cape Town, and the Rosebank Clinic, both in Johannesburg, South Africa.

The mechanism by which trauma might initiate CAPS remains uncertain, but may involve cytokine production affecting endothelial cell function and the upregulation of procoagulant molecules (Immunobiology 2005;210:727–33). Complement activation also is thought to contribute to the development of tissue injury in CAPS (Clin. Exp. Rheumatol. 2006; 24:S46–51).

Among patients in the registry, 84.5% have a past history of antiphospholipid syndrome, either primary or secondary to lupus or another connective tissue disease. All have been found to be positive for antiphospholipid antibodies, and 82% are positive for IgG anticardiolipin antibodies.

Clinical manifestations of CAPS among patients in the registry vary widely. Renal involvement has been seen in 73% of patients, pulmonary involvement has been observed in 68%, cerebral involvement in 63%, and cutaneous involvement in 58%. The pulmonary manifestations are both thrombotic and nonthrombotic and can include the adult respiratory distress syndrome and pulmonary hemorrhage.

Among patients who died and for whom necropsy findings are available, the major causes of death were cerebral, cardiac events, and infections. Microthromboses were present in 84.5%, Dr. Asherson said.

The registry is based at the systemic autoimmune diseases unit of the Hospital Clinic in Barcelona and is available at www.med.ub.es/MIMMUN/FORUM/CAPS.HTM

SAN DIEGO — Patients in the Utrecht Rheumatoid Arthritis Cohort who began treatment early in the course of disease were less likely to need joint surgery later on, Dr. Suzan M.M. Verstappen said at the annual meeting of the American College of Rheumatology.

In the ongoing Utrecht cohort study, begun in 1990, patients initially were randomized to early treatment with methotrexate, intramuscular gold, or hydroxychloroquine—or to a “pyramid” treatment approach, which was at that time the traditional paradigm. In the pyramid strategy patients first take aspirin and other NSAIDs, delaying treatment with the disease-modifying antirheumatic drugs (DMARDs), until later in the course of disease.

At the time of the first analysis, in 1994, it was apparent that patients in the early DMARD group were faring better, and henceforth, all patients were randomized to one of the three drugs, she said.

“In the present study we investigated the prevalence of joint surgery and looked at which clinical, radiographic, and demographic variables in the first 2 years of treatment—when we all know a lot of disease activity occurs—predicted later joint surgery,” said Dr. Verstappen of University Medical Center Utrecht (the Netherlands).

The cohort included 482 patients, whose mean age was 56 years and mean disease duration was 7.2 years. A total of 70% were female, and 65% were rheumatoid factor positive.

Overall, 144 patients underwent a total of 256 surgeries. Of these interventions, 32% were major surgeries such as total joint replacement, 50% were intermediate procedures such as arthrodesis, and 18% were minor interventions such as arthroscopy.

By the end of the fifth year, about 18% of patients had required at least one type of surgical intervention, according to Kaplan-Meier survival analysis. Overall mean survival time until surgery was 10 years, and for the major surgical interventions, the mean survival time was 12 years.

With regard to the need for surgical intervention among patients who responded to drug therapy, compared with those who were nonresponders, at the end of the first year no significant difference was seen between the two groups, but by the end of the second year, patients who responded to drug therapy had fewer surgical interventions, she said.

Furthermore, surgical interventions were significantly more common in those whose functional disability was worse at baseline and those who initially were randomized to NSAID therapy.

Multivariate Cox regression analyses of the 1-year data found that female gender, delayed start with DMARDs, and radiographic progression were predictive of later surgery. Hazard ratios for these variables were 1.55, 1.68, and 1.016, respectively, Dr. Verstappen said.

At the end of the second year, only a delayed start of DMARD therapy and radiographic progression were predictors, with hazard ratios of 1.73 and 1.029, respectively, on the multivariate analysis.

The need for joint surgery can be considered an outcome measure reflecting an unfavorable course of rheumatoid arthritis, and a significant number of patients still require some type of surgical intervention, Dr. Verstappen said.

“This is the first study to demonstrate that early treatment prevents later surgical intervention, and we hope that with more early aggressive treatment the percentage of patients requiring surgery later on will decrease further,” she said.

SAN DIEGO — Patients in the Utrecht Rheumatoid Arthritis Cohort who began treatment early in the course of disease were less likely to need joint surgery later on, Dr. Suzan M.M. Verstappen said at the annual meeting of the American College of Rheumatology.

In the ongoing Utrecht cohort study, begun in 1990, patients initially were randomized to early treatment with methotrexate, intramuscular gold, or hydroxychloroquine—or to a “pyramid” treatment approach, which was at that time the traditional paradigm. In the pyramid strategy patients first take aspirin and other NSAIDs, delaying treatment with the disease-modifying antirheumatic drugs (DMARDs), until later in the course of disease.

At the time of the first analysis, in 1994, it was apparent that patients in the early DMARD group were faring better, and henceforth, all patients were randomized to one of the three drugs, she said.

“In the present study we investigated the prevalence of joint surgery and looked at which clinical, radiographic, and demographic variables in the first 2 years of treatment—when we all know a lot of disease activity occurs—predicted later joint surgery,” said Dr. Verstappen of University Medical Center Utrecht (the Netherlands).

The cohort included 482 patients, whose mean age was 56 years and mean disease duration was 7.2 years. A total of 70% were female, and 65% were rheumatoid factor positive.

Overall, 144 patients underwent a total of 256 surgeries. Of these interventions, 32% were major surgeries such as total joint replacement, 50% were intermediate procedures such as arthrodesis, and 18% were minor interventions such as arthroscopy.

By the end of the fifth year, about 18% of patients had required at least one type of surgical intervention, according to Kaplan-Meier survival analysis. Overall mean survival time until surgery was 10 years, and for the major surgical interventions, the mean survival time was 12 years.

With regard to the need for surgical intervention among patients who responded to drug therapy, compared with those who were nonresponders, at the end of the first year no significant difference was seen between the two groups, but by the end of the second year, patients who responded to drug therapy had fewer surgical interventions, she said.

Furthermore, surgical interventions were significantly more common in those whose functional disability was worse at baseline and those who initially were randomized to NSAID therapy.

Multivariate Cox regression analyses of the 1-year data found that female gender, delayed start with DMARDs, and radiographic progression were predictive of later surgery. Hazard ratios for these variables were 1.55, 1.68, and 1.016, respectively, Dr. Verstappen said.

At the end of the second year, only a delayed start of DMARD therapy and radiographic progression were predictors, with hazard ratios of 1.73 and 1.029, respectively, on the multivariate analysis.

The need for joint surgery can be considered an outcome measure reflecting an unfavorable course of rheumatoid arthritis, and a significant number of patients still require some type of surgical intervention, Dr. Verstappen said.

“This is the first study to demonstrate that early treatment prevents later surgical intervention, and we hope that with more early aggressive treatment the percentage of patients requiring surgery later on will decrease further,” she said.

SAN DIEGO — Patients in the Utrecht Rheumatoid Arthritis Cohort who began treatment early in the course of disease were less likely to need joint surgery later on, Dr. Suzan M.M. Verstappen said at the annual meeting of the American College of Rheumatology.

In the ongoing Utrecht cohort study, begun in 1990, patients initially were randomized to early treatment with methotrexate, intramuscular gold, or hydroxychloroquine—or to a “pyramid” treatment approach, which was at that time the traditional paradigm. In the pyramid strategy patients first take aspirin and other NSAIDs, delaying treatment with the disease-modifying antirheumatic drugs (DMARDs), until later in the course of disease.

At the time of the first analysis, in 1994, it was apparent that patients in the early DMARD group were faring better, and henceforth, all patients were randomized to one of the three drugs, she said.

“In the present study we investigated the prevalence of joint surgery and looked at which clinical, radiographic, and demographic variables in the first 2 years of treatment—when we all know a lot of disease activity occurs—predicted later joint surgery,” said Dr. Verstappen of University Medical Center Utrecht (the Netherlands).

The cohort included 482 patients, whose mean age was 56 years and mean disease duration was 7.2 years. A total of 70% were female, and 65% were rheumatoid factor positive.

Overall, 144 patients underwent a total of 256 surgeries. Of these interventions, 32% were major surgeries such as total joint replacement, 50% were intermediate procedures such as arthrodesis, and 18% were minor interventions such as arthroscopy.

By the end of the fifth year, about 18% of patients had required at least one type of surgical intervention, according to Kaplan-Meier survival analysis. Overall mean survival time until surgery was 10 years, and for the major surgical interventions, the mean survival time was 12 years.

With regard to the need for surgical intervention among patients who responded to drug therapy, compared with those who were nonresponders, at the end of the first year no significant difference was seen between the two groups, but by the end of the second year, patients who responded to drug therapy had fewer surgical interventions, she said.

Furthermore, surgical interventions were significantly more common in those whose functional disability was worse at baseline and those who initially were randomized to NSAID therapy.

Multivariate Cox regression analyses of the 1-year data found that female gender, delayed start with DMARDs, and radiographic progression were predictive of later surgery. Hazard ratios for these variables were 1.55, 1.68, and 1.016, respectively, Dr. Verstappen said.

At the end of the second year, only a delayed start of DMARD therapy and radiographic progression were predictors, with hazard ratios of 1.73 and 1.029, respectively, on the multivariate analysis.

The need for joint surgery can be considered an outcome measure reflecting an unfavorable course of rheumatoid arthritis, and a significant number of patients still require some type of surgical intervention, Dr. Verstappen said.

“This is the first study to demonstrate that early treatment prevents later surgical intervention, and we hope that with more early aggressive treatment the percentage of patients requiring surgery later on will decrease further,” she said.

LAS VEGAS — A mycologic mystery has been brewing in the desert Southwest of the United States.

During the past dozen years, there have been 16 cases of gastrointestinal infection with Basidiobolus ranarum, a filamentous fungus previously associated almost exclusively with skin and soft tissue infections in Africa and Southeast Asia, Dr. Jerry D. Smilack said. Fifteen of the 16 cases occurred in Arizona, and 1 occurred just across the state line in St. George, Utah.

B. ranarum is present throughout the world and was first isolated more than 100 years ago from frog and lizard intestines and other environmental sources such as decaying vegetable matter. The first human infections were reported in Indonesia during the 1950s.

Basidiobolus infection, which usually occurs in children after inoculation secondary to trauma, is typically characterized by a gradually enlarging subcutaneous mass or nodule that ultimately may ulcerate.

There have been anecdotal reports of treatment with saturated solution of potassium iodide, trimethoprim-sulfamethoxazole, and antifungal agents. Skin or soft tissue infection with this pathogen has not been reported in the United States, Dr. Smilack noted at a meeting on fungal infections sponsored by Imedex.

Prior to 1995, only six cases of gastrointestinal basidiobolomycosis had been reported in the literature: one in Florida, one in Nigeria, and four in Brazil. Only two of the affected patients survived.

Cases began appearing in Arizona during the late 1990s. Typical of them was a 79-year-old man seen by Dr. Smilack at the Mayo Clinic in Scottsdale, Ariz.

The patient had experienced 4–5 weeks of anorexia, left-sided abdominal pain, and diarrhea with a 35-lb weight loss, but he reported no fever, chills, nausea, or vomiting. He had been seen at another hospital, where the work-up showed narrowing of the descending colon and a possible inflammatory or neoplastic mass. Many years earlier, he had undergone sigmoid resection for diverticular disease; he was presumed to have recurrent diverticulitis and was given antibiotics but did not respond.

On physical examination, a palpable mass was discerned in the left upper quadrant, Dr. Smilack said. The patient's vital signs were normal, as were laboratory tests with the exception of a slight elevation in blood glucose; he had type II diabetes and was taking glyburide.

On plain film x-ray, gas bubbles were seen in the left upper quadrant, displacing the colon medially, and on CT, a considerable accumulation of inflammatory material was seen in the lumen of the colon as well as external to the colon.

The patient was taken for surgery, where a large inflammatory mass was found adherent to the small bowel, spleen, kidney, and lateral abdominal wall. A partial colon resection with end-to-end anastomosis was performed.

Histopathologic evaluation of the mass revealed marked inflammation and the Splendore-Hoeppli phenomenon, in which eosinophils are deposited around the fungus. “The histopathologic appearance is virtually diagnostic,” Dr. Smilack said.

The main clinical features reported with gastrointestinal Basidiobolus infection are abdominal pain and weight loss; fever is unusual. The infection was formerly thought to be limited to the sigmoid colon, but multiple extraintestinal sites of involvement have now been reported, including the liver, stomach, and mesentery. There have been five cases of disseminated infection as well.

All the Arizona patients have been treated with surgery and itraconazole, and all have survived, Dr. Smilack said. In vitro susceptibility data suggest that ketoconazole is active against this fungus, but that fluconazole and flucytosine are inactive.

The diagnosis should be suspected in a patient who has abdominal pain, possibly with a palpable mass, especially if there is radiographic evidence of bowel wall thickening, he said. This pathogen is found in the bowel wall itself, rather than in the mucosa, so a full-thickness histopathologic examination of the bowel wall is needed. Cultures also should be done if possible. In at least two-thirds of the cases, peripheral eosinophilia also has been present, Dr. Smilack said.

Important questions about this cluster of infections remain unanswered. “The mystery is why does this infection occur? Why in Arizona? Why, in the United States, is it only a gastrointestinal infection? What is the source—something in food or water? We assume it is something ingested, but other than that, I wish I knew,” he said.

A case-control study performed by the Centers for Disease Control and Prevention sought to identify potential host and risk factors, and there was some suggestion that prior use of ranitidine was a possible risk factor (MMWR 1999;48[32]:710–3). “I personally don't think it is a risk factor. We just don't know,” he said.

It is not clear whether surgery is always needed or if molecular techniques such as polymerase chain reaction would negate the need for a tissue diagnosis or if antifungal therapy alone would suffice.

In most cases, the diagnosis has been made only after surgery, but it is conceivable that medical treatment would be adequate if the diagnosis could be made without surgery, Dr. Smilack said.

LAS VEGAS — A mycologic mystery has been brewing in the desert Southwest of the United States.

During the past dozen years, there have been 16 cases of gastrointestinal infection with Basidiobolus ranarum, a filamentous fungus previously associated almost exclusively with skin and soft tissue infections in Africa and Southeast Asia, Dr. Jerry D. Smilack said. Fifteen of the 16 cases occurred in Arizona, and 1 occurred just across the state line in St. George, Utah.

B. ranarum is present throughout the world and was first isolated more than 100 years ago from frog and lizard intestines and other environmental sources such as decaying vegetable matter. The first human infections were reported in Indonesia during the 1950s.

Basidiobolus infection, which usually occurs in children after inoculation secondary to trauma, is typically characterized by a gradually enlarging subcutaneous mass or nodule that ultimately may ulcerate.

There have been anecdotal reports of treatment with saturated solution of potassium iodide, trimethoprim-sulfamethoxazole, and antifungal agents. Skin or soft tissue infection with this pathogen has not been reported in the United States, Dr. Smilack noted at a meeting on fungal infections sponsored by Imedex.

Prior to 1995, only six cases of gastrointestinal basidiobolomycosis had been reported in the literature: one in Florida, one in Nigeria, and four in Brazil. Only two of the affected patients survived.

Cases began appearing in Arizona during the late 1990s. Typical of them was a 79-year-old man seen by Dr. Smilack at the Mayo Clinic in Scottsdale, Ariz.

The patient had experienced 4–5 weeks of anorexia, left-sided abdominal pain, and diarrhea with a 35-lb weight loss, but he reported no fever, chills, nausea, or vomiting. He had been seen at another hospital, where the work-up showed narrowing of the descending colon and a possible inflammatory or neoplastic mass. Many years earlier, he had undergone sigmoid resection for diverticular disease; he was presumed to have recurrent diverticulitis and was given antibiotics but did not respond.

On physical examination, a palpable mass was discerned in the left upper quadrant, Dr. Smilack said. The patient's vital signs were normal, as were laboratory tests with the exception of a slight elevation in blood glucose; he had type II diabetes and was taking glyburide.

On plain film x-ray, gas bubbles were seen in the left upper quadrant, displacing the colon medially, and on CT, a considerable accumulation of inflammatory material was seen in the lumen of the colon as well as external to the colon.

The patient was taken for surgery, where a large inflammatory mass was found adherent to the small bowel, spleen, kidney, and lateral abdominal wall. A partial colon resection with end-to-end anastomosis was performed.

Histopathologic evaluation of the mass revealed marked inflammation and the Splendore-Hoeppli phenomenon, in which eosinophils are deposited around the fungus. “The histopathologic appearance is virtually diagnostic,” Dr. Smilack said.

The main clinical features reported with gastrointestinal Basidiobolus infection are abdominal pain and weight loss; fever is unusual. The infection was formerly thought to be limited to the sigmoid colon, but multiple extraintestinal sites of involvement have now been reported, including the liver, stomach, and mesentery. There have been five cases of disseminated infection as well.

All the Arizona patients have been treated with surgery and itraconazole, and all have survived, Dr. Smilack said. In vitro susceptibility data suggest that ketoconazole is active against this fungus, but that fluconazole and flucytosine are inactive.

The diagnosis should be suspected in a patient who has abdominal pain, possibly with a palpable mass, especially if there is radiographic evidence of bowel wall thickening, he said. This pathogen is found in the bowel wall itself, rather than in the mucosa, so a full-thickness histopathologic examination of the bowel wall is needed. Cultures also should be done if possible. In at least two-thirds of the cases, peripheral eosinophilia also has been present, Dr. Smilack said.

Important questions about this cluster of infections remain unanswered. “The mystery is why does this infection occur? Why in Arizona? Why, in the United States, is it only a gastrointestinal infection? What is the source—something in food or water? We assume it is something ingested, but other than that, I wish I knew,” he said.

A case-control study performed by the Centers for Disease Control and Prevention sought to identify potential host and risk factors, and there was some suggestion that prior use of ranitidine was a possible risk factor (MMWR 1999;48[32]:710–3). “I personally don't think it is a risk factor. We just don't know,” he said.

It is not clear whether surgery is always needed or if molecular techniques such as polymerase chain reaction would negate the need for a tissue diagnosis or if antifungal therapy alone would suffice.

In most cases, the diagnosis has been made only after surgery, but it is conceivable that medical treatment would be adequate if the diagnosis could be made without surgery, Dr. Smilack said.

LAS VEGAS — A mycologic mystery has been brewing in the desert Southwest of the United States.

During the past dozen years, there have been 16 cases of gastrointestinal infection with Basidiobolus ranarum, a filamentous fungus previously associated almost exclusively with skin and soft tissue infections in Africa and Southeast Asia, Dr. Jerry D. Smilack said. Fifteen of the 16 cases occurred in Arizona, and 1 occurred just across the state line in St. George, Utah.

B. ranarum is present throughout the world and was first isolated more than 100 years ago from frog and lizard intestines and other environmental sources such as decaying vegetable matter. The first human infections were reported in Indonesia during the 1950s.

Basidiobolus infection, which usually occurs in children after inoculation secondary to trauma, is typically characterized by a gradually enlarging subcutaneous mass or nodule that ultimately may ulcerate.

There have been anecdotal reports of treatment with saturated solution of potassium iodide, trimethoprim-sulfamethoxazole, and antifungal agents. Skin or soft tissue infection with this pathogen has not been reported in the United States, Dr. Smilack noted at a meeting on fungal infections sponsored by Imedex.

Prior to 1995, only six cases of gastrointestinal basidiobolomycosis had been reported in the literature: one in Florida, one in Nigeria, and four in Brazil. Only two of the affected patients survived.

Cases began appearing in Arizona during the late 1990s. Typical of them was a 79-year-old man seen by Dr. Smilack at the Mayo Clinic in Scottsdale, Ariz.

The patient had experienced 4–5 weeks of anorexia, left-sided abdominal pain, and diarrhea with a 35-lb weight loss, but he reported no fever, chills, nausea, or vomiting. He had been seen at another hospital, where the work-up showed narrowing of the descending colon and a possible inflammatory or neoplastic mass. Many years earlier, he had undergone sigmoid resection for diverticular disease; he was presumed to have recurrent diverticulitis and was given antibiotics but did not respond.

On physical examination, a palpable mass was discerned in the left upper quadrant, Dr. Smilack said. The patient's vital signs were normal, as were laboratory tests with the exception of a slight elevation in blood glucose; he had type II diabetes and was taking glyburide.

On plain film x-ray, gas bubbles were seen in the left upper quadrant, displacing the colon medially, and on CT, a considerable accumulation of inflammatory material was seen in the lumen of the colon as well as external to the colon.

The patient was taken for surgery, where a large inflammatory mass was found adherent to the small bowel, spleen, kidney, and lateral abdominal wall. A partial colon resection with end-to-end anastomosis was performed.

Histopathologic evaluation of the mass revealed marked inflammation and the Splendore-Hoeppli phenomenon, in which eosinophils are deposited around the fungus. “The histopathologic appearance is virtually diagnostic,” Dr. Smilack said.

The main clinical features reported with gastrointestinal Basidiobolus infection are abdominal pain and weight loss; fever is unusual. The infection was formerly thought to be limited to the sigmoid colon, but multiple extraintestinal sites of involvement have now been reported, including the liver, stomach, and mesentery. There have been five cases of disseminated infection as well.

All the Arizona patients have been treated with surgery and itraconazole, and all have survived, Dr. Smilack said. In vitro susceptibility data suggest that ketoconazole is active against this fungus, but that fluconazole and flucytosine are inactive.

The diagnosis should be suspected in a patient who has abdominal pain, possibly with a palpable mass, especially if there is radiographic evidence of bowel wall thickening, he said. This pathogen is found in the bowel wall itself, rather than in the mucosa, so a full-thickness histopathologic examination of the bowel wall is needed. Cultures also should be done if possible. In at least two-thirds of the cases, peripheral eosinophilia also has been present, Dr. Smilack said.

Important questions about this cluster of infections remain unanswered. “The mystery is why does this infection occur? Why in Arizona? Why, in the United States, is it only a gastrointestinal infection? What is the source—something in food or water? We assume it is something ingested, but other than that, I wish I knew,” he said.

A case-control study performed by the Centers for Disease Control and Prevention sought to identify potential host and risk factors, and there was some suggestion that prior use of ranitidine was a possible risk factor (MMWR 1999;48[32]:710–3). “I personally don't think it is a risk factor. We just don't know,” he said.

It is not clear whether surgery is always needed or if molecular techniques such as polymerase chain reaction would negate the need for a tissue diagnosis or if antifungal therapy alone would suffice.

In most cases, the diagnosis has been made only after surgery, but it is conceivable that medical treatment would be adequate if the diagnosis could be made without surgery, Dr. Smilack said.

ABANO TERME, ITALY — Distinct serologic subsets of patients with scleroderma have been identified and their autoantibody profiles correlate with specific clinical phenotypes, Dr. Carlo Maurizio Montecucco said at a congress on skin, rheumatism, and autoimmunity.

The following four antibodies, noted by Dr. Montecucco, that may be found in the serum of patients with scleroderma are found in a mutually exclusive fashion and can be used as prognostic markers:

▸ Anticentromere. These antibodies are found in 20%–30% of patients with scleroderma, although geographic and ethnic differences exist, he said. Clinically, patients with these antibodies have limited cutaneous involvement but have severe Raynaud's phenomenon that can result in ulceration and amputations.

Anticentromere antibodies also are typically found in patients with CREST (calcinosis, Raynaud's, esophageal dysphagia, sclerodactyly, and telangiectasia) syndrome.

This subset of patients has little or no interstitial lung involvement. They generally have a good prognosis although they can succumb to isolated pulmonary hypertension, said Dr. Montecucco, chair of rheumatology, University of Pavia, Italy.

▸ Antitopoisomerase I. Patients who have antibodies targeting epitopes on topoisomerase I tend to have diffused or intermittent cutaneous involvement, pulmonary fibrosis, and interstitial lung disease, he said. The prognosis for the 15%–20% of patients with this autoantibody is poor.

▸ Antinucleolar. Among this group of autoantibodies, the most clinically significant are those that are directed against the small nucleolar protein fibrillarin. The 4% of scleroderma patients with antifibrillarin antibodies typically have limited cutaneous involvement but are at high risk of pulmonary hypertension and arthritis.

These antibodies are also observed in the rare case of scleroderma renal crisis occurring in patients who have only limited cutaneous disease, he said.

▸ AntiRNA-polymerase I and III. Patients with antiRNA-polymerase antibodies have diffuse cutaneous disease and cardiac involvement, and are at high risk for scleroderma renal crisis.

The prevalence of this group of antibodies is highly variable according to geography. Among whites in the United States and the United Kingdom with diffuse cutaneous involvement, an estimated 22%–47% of patients have these antibodies.

“In contrast, in our experience in Italy, only 14% of patients with diffuse cutaneous involvement are positive for these antibodies,” Dr. Montecucco said.

In Italy, the incidence of scleroderma renal crisis also is low, he noted. More definitive data on the possible relationship between antiRNA-polymerase antibodies and renal crisis may be available in the future, as an enzyme-linked immunosorbent assay (ELISA) test for these antibodies has now become commercially available and can be used for more routine screening.

The ELISA test also may allow clinicians to follow fluctuations in antibody titers. “There are some preliminary data suggesting that the titer of these antibodies might increase just before the occurrence of scleroderma renal crisis,” he said.

ABANO TERME, ITALY — Distinct serologic subsets of patients with scleroderma have been identified and their autoantibody profiles correlate with specific clinical phenotypes, Dr. Carlo Maurizio Montecucco said at a congress on skin, rheumatism, and autoimmunity.

The following four antibodies, noted by Dr. Montecucco, that may be found in the serum of patients with scleroderma are found in a mutually exclusive fashion and can be used as prognostic markers:

▸ Anticentromere. These antibodies are found in 20%–30% of patients with scleroderma, although geographic and ethnic differences exist, he said. Clinically, patients with these antibodies have limited cutaneous involvement but have severe Raynaud's phenomenon that can result in ulceration and amputations.

Anticentromere antibodies also are typically found in patients with CREST (calcinosis, Raynaud's, esophageal dysphagia, sclerodactyly, and telangiectasia) syndrome.

This subset of patients has little or no interstitial lung involvement. They generally have a good prognosis although they can succumb to isolated pulmonary hypertension, said Dr. Montecucco, chair of rheumatology, University of Pavia, Italy.

▸ Antitopoisomerase I. Patients who have antibodies targeting epitopes on topoisomerase I tend to have diffused or intermittent cutaneous involvement, pulmonary fibrosis, and interstitial lung disease, he said. The prognosis for the 15%–20% of patients with this autoantibody is poor.

▸ Antinucleolar. Among this group of autoantibodies, the most clinically significant are those that are directed against the small nucleolar protein fibrillarin. The 4% of scleroderma patients with antifibrillarin antibodies typically have limited cutaneous involvement but are at high risk of pulmonary hypertension and arthritis.

These antibodies are also observed in the rare case of scleroderma renal crisis occurring in patients who have only limited cutaneous disease, he said.

▸ AntiRNA-polymerase I and III. Patients with antiRNA-polymerase antibodies have diffuse cutaneous disease and cardiac involvement, and are at high risk for scleroderma renal crisis.

The prevalence of this group of antibodies is highly variable according to geography. Among whites in the United States and the United Kingdom with diffuse cutaneous involvement, an estimated 22%–47% of patients have these antibodies.

“In contrast, in our experience in Italy, only 14% of patients with diffuse cutaneous involvement are positive for these antibodies,” Dr. Montecucco said.

In Italy, the incidence of scleroderma renal crisis also is low, he noted. More definitive data on the possible relationship between antiRNA-polymerase antibodies and renal crisis may be available in the future, as an enzyme-linked immunosorbent assay (ELISA) test for these antibodies has now become commercially available and can be used for more routine screening.

The ELISA test also may allow clinicians to follow fluctuations in antibody titers. “There are some preliminary data suggesting that the titer of these antibodies might increase just before the occurrence of scleroderma renal crisis,” he said.

ABANO TERME, ITALY — Distinct serologic subsets of patients with scleroderma have been identified and their autoantibody profiles correlate with specific clinical phenotypes, Dr. Carlo Maurizio Montecucco said at a congress on skin, rheumatism, and autoimmunity.

The following four antibodies, noted by Dr. Montecucco, that may be found in the serum of patients with scleroderma are found in a mutually exclusive fashion and can be used as prognostic markers:

▸ Anticentromere. These antibodies are found in 20%–30% of patients with scleroderma, although geographic and ethnic differences exist, he said. Clinically, patients with these antibodies have limited cutaneous involvement but have severe Raynaud's phenomenon that can result in ulceration and amputations.

Anticentromere antibodies also are typically found in patients with CREST (calcinosis, Raynaud's, esophageal dysphagia, sclerodactyly, and telangiectasia) syndrome.

This subset of patients has little or no interstitial lung involvement. They generally have a good prognosis although they can succumb to isolated pulmonary hypertension, said Dr. Montecucco, chair of rheumatology, University of Pavia, Italy.

▸ Antitopoisomerase I. Patients who have antibodies targeting epitopes on topoisomerase I tend to have diffused or intermittent cutaneous involvement, pulmonary fibrosis, and interstitial lung disease, he said. The prognosis for the 15%–20% of patients with this autoantibody is poor.

▸ Antinucleolar. Among this group of autoantibodies, the most clinically significant are those that are directed against the small nucleolar protein fibrillarin. The 4% of scleroderma patients with antifibrillarin antibodies typically have limited cutaneous involvement but are at high risk of pulmonary hypertension and arthritis.

These antibodies are also observed in the rare case of scleroderma renal crisis occurring in patients who have only limited cutaneous disease, he said.

▸ AntiRNA-polymerase I and III. Patients with antiRNA-polymerase antibodies have diffuse cutaneous disease and cardiac involvement, and are at high risk for scleroderma renal crisis.

The prevalence of this group of antibodies is highly variable according to geography. Among whites in the United States and the United Kingdom with diffuse cutaneous involvement, an estimated 22%–47% of patients have these antibodies.

“In contrast, in our experience in Italy, only 14% of patients with diffuse cutaneous involvement are positive for these antibodies,” Dr. Montecucco said.

In Italy, the incidence of scleroderma renal crisis also is low, he noted. More definitive data on the possible relationship between antiRNA-polymerase antibodies and renal crisis may be available in the future, as an enzyme-linked immunosorbent assay (ELISA) test for these antibodies has now become commercially available and can be used for more routine screening.

The ELISA test also may allow clinicians to follow fluctuations in antibody titers. “There are some preliminary data suggesting that the titer of these antibodies might increase just before the occurrence of scleroderma renal crisis,” he said.

ABANO TERME, ITALY — Thalidomide offers an effective option for the treatment of refractory cutaneous lupus, but close monitoring is needed so the drug can be stopped at the first sign of peripheral neuropathy, Dr. Chiara Briani said at a congress on skin, rheumatism, and autoimmunity.

This drug is being used increasingly for cutaneous lupus erythematosus that does not respond to conventional therapy, but its use is limited by adverse effects, in particular a sensory, axonal peripheral neuropathy.

Retrospective investigations of thalidomide in cutaneous disorders have suggested that the incidence of peripheral neuropathy can range from less than 1% to 70%.

It's not clear whether neuropathy is related to cumulative thalidomide dose, Dr. Briani said.

To address these concerns, 14 patients who had not responded to antimalarial agents were followed prospectively, undergoing regular biochemical, dermatologic, rheumatologic, and neurologic evaluations. All were women and ranged in age from 23 to 56 years. The teratogenic effects of thalidomide can be avoided among women of childbearing age with proper contraceptive measures, and strict regulations in this regard are in place in Europe, she said.

A 50% decline in sural sensory nerve action potential (SNAP) amplitude, with relative conservation of sensory nerve conduction velocity, was considered indicative of sensory axonal peripheral neuropathy. Whenever a patient reached a 50% decline in SNAP, the thalidomide dose was lowered, and the drug was stopped when a decline of 70% was reached.

The baseline dose was 100 mg/day of thalidomide, and after 1 month the dose was tapered to 50 mg/day and subsequently to 50 mg every other day, unless peripheral neuropathy developed.

At baseline one patient already had lupus-related peripheral neuropathy, and another patient also had diabetes, said Dr. Briani of the department of neurosciences, University of Padua (Italy).

The median follow-up was 14 months, and the mean cumulative thalidomide dose was 23 g.

All patients showed “dramatic improvement” in their cutaneous symptoms within 1–2 months of starting therapy, she said.

Neuropathy occurred in two-thirds (10) of the patients during the course of treatment as demonstrated on electrophysiologic testing, but only 6 complained of sensory symptoms.

Moreover, in patients who became symptomatic, the electrophysiologic changes often preceded the clinical symptoms, heightening the significance of monitoring in patients undergoing treatment with thalidomide, she said.

“We did not find a correlation between total thalidomide dose or duration of therapy and the occurrence of neuropathy,” she said.

One patient had no signs of neuropathy after 23 months and a total dose of 30 g, while another developed peripheral neuropathy after only 4.5 months and a cumulative dose of 9.5 g.

Nor was there a clear association with underlying risk factors: The patient with diabetes did not develop a 50% decrease in sural SNAP until 14 months of treatment, and the patient who had signs of neuropathy already present at baseline showed only a 31.6% decrease. Pharmacogenetic susceptibility or other individual factors may contribute (Autoimmunity 2005;38:549–55).

In four patients the neuropathy resolved completely, in one patient partial improvement was seen, but in five patients there were no sural SNAP changes 15 months after thalidomide treatment was withdrawn.

For long-term treatment with thalidomide, therefore, close electrophysiologic follow-up is recommended so that the drug can be reduced or withdrawn as soon as subclinical signs of neuropathy appear, Dr. Briani said.

ABANO TERME, ITALY — Thalidomide offers an effective option for the treatment of refractory cutaneous lupus, but close monitoring is needed so the drug can be stopped at the first sign of peripheral neuropathy, Dr. Chiara Briani said at a congress on skin, rheumatism, and autoimmunity.

This drug is being used increasingly for cutaneous lupus erythematosus that does not respond to conventional therapy, but its use is limited by adverse effects, in particular a sensory, axonal peripheral neuropathy.

Retrospective investigations of thalidomide in cutaneous disorders have suggested that the incidence of peripheral neuropathy can range from less than 1% to 70%.

It's not clear whether neuropathy is related to cumulative thalidomide dose, Dr. Briani said.

To address these concerns, 14 patients who had not responded to antimalarial agents were followed prospectively, undergoing regular biochemical, dermatologic, rheumatologic, and neurologic evaluations. All were women and ranged in age from 23 to 56 years. The teratogenic effects of thalidomide can be avoided among women of childbearing age with proper contraceptive measures, and strict regulations in this regard are in place in Europe, she said.

A 50% decline in sural sensory nerve action potential (SNAP) amplitude, with relative conservation of sensory nerve conduction velocity, was considered indicative of sensory axonal peripheral neuropathy. Whenever a patient reached a 50% decline in SNAP, the thalidomide dose was lowered, and the drug was stopped when a decline of 70% was reached.

The baseline dose was 100 mg/day of thalidomide, and after 1 month the dose was tapered to 50 mg/day and subsequently to 50 mg every other day, unless peripheral neuropathy developed.

At baseline one patient already had lupus-related peripheral neuropathy, and another patient also had diabetes, said Dr. Briani of the department of neurosciences, University of Padua (Italy).

The median follow-up was 14 months, and the mean cumulative thalidomide dose was 23 g.

All patients showed “dramatic improvement” in their cutaneous symptoms within 1–2 months of starting therapy, she said.

Neuropathy occurred in two-thirds (10) of the patients during the course of treatment as demonstrated on electrophysiologic testing, but only 6 complained of sensory symptoms.

Moreover, in patients who became symptomatic, the electrophysiologic changes often preceded the clinical symptoms, heightening the significance of monitoring in patients undergoing treatment with thalidomide, she said.

“We did not find a correlation between total thalidomide dose or duration of therapy and the occurrence of neuropathy,” she said.

One patient had no signs of neuropathy after 23 months and a total dose of 30 g, while another developed peripheral neuropathy after only 4.5 months and a cumulative dose of 9.5 g.

Nor was there a clear association with underlying risk factors: The patient with diabetes did not develop a 50% decrease in sural SNAP until 14 months of treatment, and the patient who had signs of neuropathy already present at baseline showed only a 31.6% decrease. Pharmacogenetic susceptibility or other individual factors may contribute (Autoimmunity 2005;38:549–55).

In four patients the neuropathy resolved completely, in one patient partial improvement was seen, but in five patients there were no sural SNAP changes 15 months after thalidomide treatment was withdrawn.

For long-term treatment with thalidomide, therefore, close electrophysiologic follow-up is recommended so that the drug can be reduced or withdrawn as soon as subclinical signs of neuropathy appear, Dr. Briani said.

ABANO TERME, ITALY — Thalidomide offers an effective option for the treatment of refractory cutaneous lupus, but close monitoring is needed so the drug can be stopped at the first sign of peripheral neuropathy, Dr. Chiara Briani said at a congress on skin, rheumatism, and autoimmunity.

This drug is being used increasingly for cutaneous lupus erythematosus that does not respond to conventional therapy, but its use is limited by adverse effects, in particular a sensory, axonal peripheral neuropathy.

Retrospective investigations of thalidomide in cutaneous disorders have suggested that the incidence of peripheral neuropathy can range from less than 1% to 70%.

It's not clear whether neuropathy is related to cumulative thalidomide dose, Dr. Briani said.

To address these concerns, 14 patients who had not responded to antimalarial agents were followed prospectively, undergoing regular biochemical, dermatologic, rheumatologic, and neurologic evaluations. All were women and ranged in age from 23 to 56 years. The teratogenic effects of thalidomide can be avoided among women of childbearing age with proper contraceptive measures, and strict regulations in this regard are in place in Europe, she said.

A 50% decline in sural sensory nerve action potential (SNAP) amplitude, with relative conservation of sensory nerve conduction velocity, was considered indicative of sensory axonal peripheral neuropathy. Whenever a patient reached a 50% decline in SNAP, the thalidomide dose was lowered, and the drug was stopped when a decline of 70% was reached.

The baseline dose was 100 mg/day of thalidomide, and after 1 month the dose was tapered to 50 mg/day and subsequently to 50 mg every other day, unless peripheral neuropathy developed.

At baseline one patient already had lupus-related peripheral neuropathy, and another patient also had diabetes, said Dr. Briani of the department of neurosciences, University of Padua (Italy).

The median follow-up was 14 months, and the mean cumulative thalidomide dose was 23 g.

All patients showed “dramatic improvement” in their cutaneous symptoms within 1–2 months of starting therapy, she said.

Neuropathy occurred in two-thirds (10) of the patients during the course of treatment as demonstrated on electrophysiologic testing, but only 6 complained of sensory symptoms.

Moreover, in patients who became symptomatic, the electrophysiologic changes often preceded the clinical symptoms, heightening the significance of monitoring in patients undergoing treatment with thalidomide, she said.

“We did not find a correlation between total thalidomide dose or duration of therapy and the occurrence of neuropathy,” she said.

One patient had no signs of neuropathy after 23 months and a total dose of 30 g, while another developed peripheral neuropathy after only 4.5 months and a cumulative dose of 9.5 g.

Nor was there a clear association with underlying risk factors: The patient with diabetes did not develop a 50% decrease in sural SNAP until 14 months of treatment, and the patient who had signs of neuropathy already present at baseline showed only a 31.6% decrease. Pharmacogenetic susceptibility or other individual factors may contribute (Autoimmunity 2005;38:549–55).

In four patients the neuropathy resolved completely, in one patient partial improvement was seen, but in five patients there were no sural SNAP changes 15 months after thalidomide treatment was withdrawn.

For long-term treatment with thalidomide, therefore, close electrophysiologic follow-up is recommended so that the drug can be reduced or withdrawn as soon as subclinical signs of neuropathy appear, Dr. Briani said.

LAS VEGAS — A mycologic mystery has been brewing in the desert Southwest of the United States.

During the past dozen years, there have been 16 cases of gastrointestinal infection with Basidiobolus ranarum, a filamentous fungus previously associated almost exclusively with skin and soft tissue infections in Africa and Southeast Asia, Dr. Jerry D. Smilack said. Fifteen of the 16 cases occurred in Arizona, and 1 occurred just across the state line in St. George, Utah.

B. ranarum is present throughout the world and was first isolated more than 100 years ago from frog and lizard intestines and other environmental sources such as decaying vegetable matter. The first human infections were reported in Indonesia during the 1950s.

Basidiobolus infection, which usually occurs in children after inoculation secondary to trauma, is typically characterized by a gradually enlarging subcutaneous mass or nodule that ultimately may ulcerate.

There have been anecdotal reports of treatment with a saturated solution of potassium iodide, trimethoprim-sulfamethoxazole, and antifungal agents. Skin or soft tissue infection with this pathogen has not been reported in the United States, Dr. Smilack noted at a meeting on fungal infections sponsored by Imedex.

Prior to 1995, only six cases of gastrointestinal basidiobolomycosis had been reported in the literature: one in Florida, one in Nigeria, and four in Brazil. Only two of the affected patients survived.

Cases began appearing in Arizona during the late 1990s. Typical of them was a 79-year-old man seen by Dr. Smilack at the Mayo Clinic in Scottsdale, Ariz.

The patient had experienced 4–5 weeks of anorexia, left-sided abdominal pain, and diarrhea with a 35-lb weight loss, but he reported no fever, chills, nausea, or vomiting. He had been seen at another hospital, where the work-up showed narrowing of the descending colon and a possible inflammatory or neoplastic mass. Many years earlier, he had undergone sigmoid resection for diverticular disease; he was presumed to have recurrent diverticulitis and was given antibiotics but did not respond.

On physical examination, a palpable mass was discerned in the left upper quadrant, Dr. Smilack said. The patient's vital signs were normal, as were laboratory tests with the exception of a slight elevation in blood glucose; he had type II diabetes and was taking glyburide.

On plain film x-ray, gas bubbles were seen in the left upper quadrant, displacing the colon medially, and on CT, a considerable accumulation of inflammatory material was seen in the lumen of the colon as well as external to the colon.

The patient was taken for surgery, where a large inflammatory mass was found adherent to the small bowel, spleen, kidney, and lateral abdominal wall. A partial colon resection with end-to-end anastomosis was performed.

Histopathologic evaluation of the mass revealed marked inflammation and the Splendore-Hoeppli phenomenon, in which eosinophils are deposited around the fungus. “The histopathologic appearance is virtually diagnostic,” Dr. Smilack said.

The main clinical features reported with gastrointestinal Basidiobolus infection are abdominal pain and weight loss; fever is unusual. The infection was formerly thought to be limited to the sigmoid colon, but multiple extraintestinal sites of involvement have now been reported, including the liver, stomach, and mesentery. There have been five cases of disseminated infection as well.

All the Arizona patients have been treated with surgery and itraconazole, and all have survived, Dr. Smilack said. In vitro susceptibility data suggest that ketoconazole is active against this fungus but that fluconazole and flucytosine are inactive.

The diagnosis should be suspected in a patient who has abdominal pain, possibly with a palpable mass, especially if there is radiographic evidence of bowel-wall thickening, he said. This pathogen is found in the bowel wall itself, rather than in the mucosa, so a full-thickness histopathologic examination of the bowel wall is needed. Cultures also should be done if possible. In at least two-thirds of the cases, peripheral eosinophilia also has been present, Dr. Smilack said.

Important questions about this cluster of infections remain unanswered. “The mystery is, why does this infection occur? Why in Arizona? Why in the United States? Is it only a gastrointestinal infection? What is the source—something in food or water? We assume it is something ingested, but other than that, I wish I knew,” he said.

A case-control study performed by the Centers for Disease Control and Prevention sought to identify potential host and risk factors, and there was some suggestion that prior use of ranitidine was a possible risk factor (MMWR 1999;48:710–3).“I personally don't think it is a risk factor. We just don't know,” he said.

LAS VEGAS — A mycologic mystery has been brewing in the desert Southwest of the United States.

During the past dozen years, there have been 16 cases of gastrointestinal infection with Basidiobolus ranarum, a filamentous fungus previously associated almost exclusively with skin and soft tissue infections in Africa and Southeast Asia, Dr. Jerry D. Smilack said. Fifteen of the 16 cases occurred in Arizona, and 1 occurred just across the state line in St. George, Utah.

B. ranarum is present throughout the world and was first isolated more than 100 years ago from frog and lizard intestines and other environmental sources such as decaying vegetable matter. The first human infections were reported in Indonesia during the 1950s.

Basidiobolus infection, which usually occurs in children after inoculation secondary to trauma, is typically characterized by a gradually enlarging subcutaneous mass or nodule that ultimately may ulcerate.

There have been anecdotal reports of treatment with a saturated solution of potassium iodide, trimethoprim-sulfamethoxazole, and antifungal agents. Skin or soft tissue infection with this pathogen has not been reported in the United States, Dr. Smilack noted at a meeting on fungal infections sponsored by Imedex.

Prior to 1995, only six cases of gastrointestinal basidiobolomycosis had been reported in the literature: one in Florida, one in Nigeria, and four in Brazil. Only two of the affected patients survived.

Cases began appearing in Arizona during the late 1990s. Typical of them was a 79-year-old man seen by Dr. Smilack at the Mayo Clinic in Scottsdale, Ariz.

The patient had experienced 4–5 weeks of anorexia, left-sided abdominal pain, and diarrhea with a 35-lb weight loss, but he reported no fever, chills, nausea, or vomiting. He had been seen at another hospital, where the work-up showed narrowing of the descending colon and a possible inflammatory or neoplastic mass. Many years earlier, he had undergone sigmoid resection for diverticular disease; he was presumed to have recurrent diverticulitis and was given antibiotics but did not respond.

On physical examination, a palpable mass was discerned in the left upper quadrant, Dr. Smilack said. The patient's vital signs were normal, as were laboratory tests with the exception of a slight elevation in blood glucose; he had type II diabetes and was taking glyburide.

On plain film x-ray, gas bubbles were seen in the left upper quadrant, displacing the colon medially, and on CT, a considerable accumulation of inflammatory material was seen in the lumen of the colon as well as external to the colon.

The patient was taken for surgery, where a large inflammatory mass was found adherent to the small bowel, spleen, kidney, and lateral abdominal wall. A partial colon resection with end-to-end anastomosis was performed.

Histopathologic evaluation of the mass revealed marked inflammation and the Splendore-Hoeppli phenomenon, in which eosinophils are deposited around the fungus. “The histopathologic appearance is virtually diagnostic,” Dr. Smilack said.

The main clinical features reported with gastrointestinal Basidiobolus infection are abdominal pain and weight loss; fever is unusual. The infection was formerly thought to be limited to the sigmoid colon, but multiple extraintestinal sites of involvement have now been reported, including the liver, stomach, and mesentery. There have been five cases of disseminated infection as well.

All the Arizona patients have been treated with surgery and itraconazole, and all have survived, Dr. Smilack said. In vitro susceptibility data suggest that ketoconazole is active against this fungus but that fluconazole and flucytosine are inactive.

The diagnosis should be suspected in a patient who has abdominal pain, possibly with a palpable mass, especially if there is radiographic evidence of bowel-wall thickening, he said. This pathogen is found in the bowel wall itself, rather than in the mucosa, so a full-thickness histopathologic examination of the bowel wall is needed. Cultures also should be done if possible. In at least two-thirds of the cases, peripheral eosinophilia also has been present, Dr. Smilack said.

Important questions about this cluster of infections remain unanswered. “The mystery is, why does this infection occur? Why in Arizona? Why in the United States? Is it only a gastrointestinal infection? What is the source—something in food or water? We assume it is something ingested, but other than that, I wish I knew,” he said.

A case-control study performed by the Centers for Disease Control and Prevention sought to identify potential host and risk factors, and there was some suggestion that prior use of ranitidine was a possible risk factor (MMWR 1999;48:710–3).“I personally don't think it is a risk factor. We just don't know,” he said.

LAS VEGAS — A mycologic mystery has been brewing in the desert Southwest of the United States.

During the past dozen years, there have been 16 cases of gastrointestinal infection with Basidiobolus ranarum, a filamentous fungus previously associated almost exclusively with skin and soft tissue infections in Africa and Southeast Asia, Dr. Jerry D. Smilack said. Fifteen of the 16 cases occurred in Arizona, and 1 occurred just across the state line in St. George, Utah.

B. ranarum is present throughout the world and was first isolated more than 100 years ago from frog and lizard intestines and other environmental sources such as decaying vegetable matter. The first human infections were reported in Indonesia during the 1950s.

Basidiobolus infection, which usually occurs in children after inoculation secondary to trauma, is typically characterized by a gradually enlarging subcutaneous mass or nodule that ultimately may ulcerate.

There have been anecdotal reports of treatment with a saturated solution of potassium iodide, trimethoprim-sulfamethoxazole, and antifungal agents. Skin or soft tissue infection with this pathogen has not been reported in the United States, Dr. Smilack noted at a meeting on fungal infections sponsored by Imedex.

Prior to 1995, only six cases of gastrointestinal basidiobolomycosis had been reported in the literature: one in Florida, one in Nigeria, and four in Brazil. Only two of the affected patients survived.

Cases began appearing in Arizona during the late 1990s. Typical of them was a 79-year-old man seen by Dr. Smilack at the Mayo Clinic in Scottsdale, Ariz.

The patient had experienced 4–5 weeks of anorexia, left-sided abdominal pain, and diarrhea with a 35-lb weight loss, but he reported no fever, chills, nausea, or vomiting. He had been seen at another hospital, where the work-up showed narrowing of the descending colon and a possible inflammatory or neoplastic mass. Many years earlier, he had undergone sigmoid resection for diverticular disease; he was presumed to have recurrent diverticulitis and was given antibiotics but did not respond.

On physical examination, a palpable mass was discerned in the left upper quadrant, Dr. Smilack said. The patient's vital signs were normal, as were laboratory tests with the exception of a slight elevation in blood glucose; he had type II diabetes and was taking glyburide.

On plain film x-ray, gas bubbles were seen in the left upper quadrant, displacing the colon medially, and on CT, a considerable accumulation of inflammatory material was seen in the lumen of the colon as well as external to the colon.

The patient was taken for surgery, where a large inflammatory mass was found adherent to the small bowel, spleen, kidney, and lateral abdominal wall. A partial colon resection with end-to-end anastomosis was performed.

Histopathologic evaluation of the mass revealed marked inflammation and the Splendore-Hoeppli phenomenon, in which eosinophils are deposited around the fungus. “The histopathologic appearance is virtually diagnostic,” Dr. Smilack said.

The main clinical features reported with gastrointestinal Basidiobolus infection are abdominal pain and weight loss; fever is unusual. The infection was formerly thought to be limited to the sigmoid colon, but multiple extraintestinal sites of involvement have now been reported, including the liver, stomach, and mesentery. There have been five cases of disseminated infection as well.

All the Arizona patients have been treated with surgery and itraconazole, and all have survived, Dr. Smilack said. In vitro susceptibility data suggest that ketoconazole is active against this fungus but that fluconazole and flucytosine are inactive.

The diagnosis should be suspected in a patient who has abdominal pain, possibly with a palpable mass, especially if there is radiographic evidence of bowel-wall thickening, he said. This pathogen is found in the bowel wall itself, rather than in the mucosa, so a full-thickness histopathologic examination of the bowel wall is needed. Cultures also should be done if possible. In at least two-thirds of the cases, peripheral eosinophilia also has been present, Dr. Smilack said.

Important questions about this cluster of infections remain unanswered. “The mystery is, why does this infection occur? Why in Arizona? Why in the United States? Is it only a gastrointestinal infection? What is the source—something in food or water? We assume it is something ingested, but other than that, I wish I knew,” he said.

A case-control study performed by the Centers for Disease Control and Prevention sought to identify potential host and risk factors, and there was some suggestion that prior use of ranitidine was a possible risk factor (MMWR 1999;48:710–3).“I personally don't think it is a risk factor. We just don't know,” he said.

Diagnosis: Idiopathic Hypereosinophilia

LONDON — Laboratory evaluation also revealed anemia and an elevated erythrocyte sedimentation rate. Histology findings included hyperkeratosis, irregular acanthosis, and a mixed inflammatory infiltrate of lymphocytes, plasmocytes, and numerous eosinophils. Thrombosis of small vessels in the dermis and edema of the vessel walls also was noted.

No cause for her eosinophilia could be identified despite a meticulous search. Reactive eosinophilia, such as can occur with parasitic infections, and clonal disorders of the bone marrow associated with eosinophilia, such as various types of leukemia, were ruled out.

The diagnosis, therefore, was idiopathic hypereosinophilia syndrome, Dr. Mira Kadurina said in a poster presentation at the 14th Congress of the European Academy of Dermatology and Venereology.

Some investigators have proposed that idiopathic hypereosinophilia syndrome is a Th2-mediated disease characterized by clonal expansion of a T-cell population able to produce interleukin (IL)-5 and IL-4. Pathogenic T cells—usually CD3 negative, CD4 positive—display an aberrant surface phenotype.

The clinical presentation is heterogeneous and includes myeloproliferative and lymphocytic variants. In the more aggressive myeloid variant, patients can have chromosomal abnormalities, hepatosplenomegaly, cardiac complications, and myeloid malignancies. The prognosis is poor, said Dr. Kadurina of the department of dermatology and venereology at the Military Medical Academy in Sofia, Bulgaria.

The lymphocytic variant may be a primitive lymphoid disorder characterized by nonmalignant expansion of an IL-5-producing T-cell population. Cutaneous manifestations can include pruritus, eczema, erythroderma, and urticaria.

Immunohistochemical staining of tissue specimens from this patient revealed the presence of CD43-positive and CD4-positive cells, as well as CD8-negative and CD20-negative lymphocytes.

She was treated with prednisone, 60 mg/day, which was gradually tapered to 15 mg/day over a month's time. After treatment was withdrawn she once again developed disseminated, erythematous, pruritic lesions, this time involving the hands and feet. The fingers became painful, cyanotic, and swollen, initially after exposure to cold. A painful ulcer appeared on the third finger of the right hand.

Raynaud's phenomenon, identified by capillaroscopy, was an unusual cutaneous complication of the idiopathic hypereosinophilia syndrome in this patient, Dr. Kadurina wrote.

The administration of methylprednisolone, 60 mg/day, and pentoxifylline, 800 mg/day, led to a remission; the corticosteroid dosage was tapered to 5 mg/day over 45 days.

During 3 months of follow-up no new lesions appeared, the vasoconstriction of the patient's hands disappeared, and the finger ulcer healed.

A proposed explanation for the development of Raynaud's phenomenon and digital gangrene in association with hypereosinophilia, as occurred in this patient, is that major basic protein and eosinophil cationic proteins located in the eosinophil granule matrix contributed to the formation of microthrombi.

Efforts continue to further explicate the pathogenesis. "Future progress in unveiling variants of the syndrome is likely to consign to history the term idiopathic, replacing it with an array of well-defined hematologic disorders," Dr. Kadurina wrote.

Histology findings included a mixed inflammatory infiltrate of lymphocytes, plasmocytes, and numerous eosinophils. Courtesy Dr. Mira Kadurina

Diagnosis: Idiopathic Hypereosinophilia

LONDON — Laboratory evaluation also revealed anemia and an elevated erythrocyte sedimentation rate. Histology findings included hyperkeratosis, irregular acanthosis, and a mixed inflammatory infiltrate of lymphocytes, plasmocytes, and numerous eosinophils. Thrombosis of small vessels in the dermis and edema of the vessel walls also was noted.

No cause for her eosinophilia could be identified despite a meticulous search. Reactive eosinophilia, such as can occur with parasitic infections, and clonal disorders of the bone marrow associated with eosinophilia, such as various types of leukemia, were ruled out.

The diagnosis, therefore, was idiopathic hypereosinophilia syndrome, Dr. Mira Kadurina said in a poster presentation at the 14th Congress of the European Academy of Dermatology and Venereology.

Some investigators have proposed that idiopathic hypereosinophilia syndrome is a Th2-mediated disease characterized by clonal expansion of a T-cell population able to produce interleukin (IL)-5 and IL-4. Pathogenic T cells—usually CD3 negative, CD4 positive—display an aberrant surface phenotype.

The clinical presentation is heterogeneous and includes myeloproliferative and lymphocytic variants. In the more aggressive myeloid variant, patients can have chromosomal abnormalities, hepatosplenomegaly, cardiac complications, and myeloid malignancies. The prognosis is poor, said Dr. Kadurina of the department of dermatology and venereology at the Military Medical Academy in Sofia, Bulgaria.

The lymphocytic variant may be a primitive lymphoid disorder characterized by nonmalignant expansion of an IL-5-producing T-cell population. Cutaneous manifestations can include pruritus, eczema, erythroderma, and urticaria.

Immunohistochemical staining of tissue specimens from this patient revealed the presence of CD43-positive and CD4-positive cells, as well as CD8-negative and CD20-negative lymphocytes.

She was treated with prednisone, 60 mg/day, which was gradually tapered to 15 mg/day over a month's time. After treatment was withdrawn she once again developed disseminated, erythematous, pruritic lesions, this time involving the hands and feet. The fingers became painful, cyanotic, and swollen, initially after exposure to cold. A painful ulcer appeared on the third finger of the right hand.

Raynaud's phenomenon, identified by capillaroscopy, was an unusual cutaneous complication of the idiopathic hypereosinophilia syndrome in this patient, Dr. Kadurina wrote.

The administration of methylprednisolone, 60 mg/day, and pentoxifylline, 800 mg/day, led to a remission; the corticosteroid dosage was tapered to 5 mg/day over 45 days.

During 3 months of follow-up no new lesions appeared, the vasoconstriction of the patient's hands disappeared, and the finger ulcer healed.

A proposed explanation for the development of Raynaud's phenomenon and digital gangrene in association with hypereosinophilia, as occurred in this patient, is that major basic protein and eosinophil cationic proteins located in the eosinophil granule matrix contributed to the formation of microthrombi.

Efforts continue to further explicate the pathogenesis. "Future progress in unveiling variants of the syndrome is likely to consign to history the term idiopathic, replacing it with an array of well-defined hematologic disorders," Dr. Kadurina wrote.

Histology findings included a mixed inflammatory infiltrate of lymphocytes, plasmocytes, and numerous eosinophils. Courtesy Dr. Mira Kadurina

Diagnosis: Idiopathic Hypereosinophilia

LONDON — Laboratory evaluation also revealed anemia and an elevated erythrocyte sedimentation rate. Histology findings included hyperkeratosis, irregular acanthosis, and a mixed inflammatory infiltrate of lymphocytes, plasmocytes, and numerous eosinophils. Thrombosis of small vessels in the dermis and edema of the vessel walls also was noted.

No cause for her eosinophilia could be identified despite a meticulous search. Reactive eosinophilia, such as can occur with parasitic infections, and clonal disorders of the bone marrow associated with eosinophilia, such as various types of leukemia, were ruled out.

The diagnosis, therefore, was idiopathic hypereosinophilia syndrome, Dr. Mira Kadurina said in a poster presentation at the 14th Congress of the European Academy of Dermatology and Venereology.

Some investigators have proposed that idiopathic hypereosinophilia syndrome is a Th2-mediated disease characterized by clonal expansion of a T-cell population able to produce interleukin (IL)-5 and IL-4. Pathogenic T cells—usually CD3 negative, CD4 positive—display an aberrant surface phenotype.

The clinical presentation is heterogeneous and includes myeloproliferative and lymphocytic variants. In the more aggressive myeloid variant, patients can have chromosomal abnormalities, hepatosplenomegaly, cardiac complications, and myeloid malignancies. The prognosis is poor, said Dr. Kadurina of the department of dermatology and venereology at the Military Medical Academy in Sofia, Bulgaria.

The lymphocytic variant may be a primitive lymphoid disorder characterized by nonmalignant expansion of an IL-5-producing T-cell population. Cutaneous manifestations can include pruritus, eczema, erythroderma, and urticaria.

Immunohistochemical staining of tissue specimens from this patient revealed the presence of CD43-positive and CD4-positive cells, as well as CD8-negative and CD20-negative lymphocytes.

She was treated with prednisone, 60 mg/day, which was gradually tapered to 15 mg/day over a month's time. After treatment was withdrawn she once again developed disseminated, erythematous, pruritic lesions, this time involving the hands and feet. The fingers became painful, cyanotic, and swollen, initially after exposure to cold. A painful ulcer appeared on the third finger of the right hand.

Raynaud's phenomenon, identified by capillaroscopy, was an unusual cutaneous complication of the idiopathic hypereosinophilia syndrome in this patient, Dr. Kadurina wrote.

The administration of methylprednisolone, 60 mg/day, and pentoxifylline, 800 mg/day, led to a remission; the corticosteroid dosage was tapered to 5 mg/day over 45 days.

During 3 months of follow-up no new lesions appeared, the vasoconstriction of the patient's hands disappeared, and the finger ulcer healed.

A proposed explanation for the development of Raynaud's phenomenon and digital gangrene in association with hypereosinophilia, as occurred in this patient, is that major basic protein and eosinophil cationic proteins located in the eosinophil granule matrix contributed to the formation of microthrombi.

Efforts continue to further explicate the pathogenesis. "Future progress in unveiling variants of the syndrome is likely to consign to history the term idiopathic, replacing it with an array of well-defined hematologic disorders," Dr. Kadurina wrote.

Histology findings included a mixed inflammatory infiltrate of lymphocytes, plasmocytes, and numerous eosinophils. Courtesy Dr. Mira Kadurina