Young Age, Mucosal Involvement Predict Relapses in Pemphigus

SORRENTO, ITALY — Patients with pemphigus who are younger than 40 years at the time of diagnosis and whose first remission is brief are likely to have a more severe course of disease and multiple relapses, Dr. David Mimouni said at the Fifth International Congress on Autoimmunity.

Much remains unknown about the natural history of pemphigus. In an attempt to address this, a survey was undertaken of 155 patients diagnosed with some form of pemphigus and treated at an Israeli center between 1976 and 2004.

Follow-up for the patients ranged from 4 to 28 years. Of these patients, 94 were female. The age distribution at disease onset was typical of pemphigus, peaking between 40 and 50 years, said Dr. Mimouni of the department of dermatology, Rabin Medical Center, Petah Tiqwa, Israel.

Pemphigus vulgaris was the diagnosis in 144 patients. The remainder had diagnoses of pemphigus foliaceus, in which only the skin is involved and the mucous membranes are spared; pemphigus erythematosus, with features of both pemphigus and lupus; and paraneoplastic pemphigus.

In only 16 patients could a precipitating factor such as stress, drugs, or sun exposure be identified, he said.

The initial site of involvement was the mucosa alone in 50%, the skin alone in 47%, and both in 3%. At the time of follow-up, however, involvement limited to the mucosa or skin was seen only in 21% and 24%, respectively, while both sites were affected in 55%, Dr. Mimouni said.

A total of 91 patients were of Ashkenazi Jewish origin, while 58 were of Sephardic origin, and 6 were Arab. At the time of follow-up, the Sephardic patients were significantly less likely to be in remission than were the Ashkenazi, which was surprising, because a strong genetic link had previously been established for Ashkenazi origin, Dr. Mimouni said.

Younger patients and those whose initial remission lasted less than a year also were less likely to be in remission at the time of follow-up, as were those with mucosal involvement.

All patients had been treated with high doses of steroids, usually between 1.5 and 2 mg/kg per day, for periods up to 10 years. Most also had adjuvant therapy, most commonly with azathioprine, although recently other agents such as mycophenolate mofetil had been used.

Only 2% of the study patients had never had a relapse following treatment, while 40% had one to two relapses, and 58% had more than three, he said.

A total of 16 patients died. The causes of death were cancer, ischemic heart disease, and pulmonary embolism. None of the deaths was directly related to pemphigus, which represents a marked change from 1950, when 90% of patients would have died of pemphigus within 2 years, Dr. Mimouni said.

This study suggests that although there still is no cure for pemphigus, the morbidity and mortality associated with the disease have decreased significantly.

Progress has also been made in deciphering some of the underlying autoimmune processes in these conditions. For example, it is now known that pemphigus vulgaris is characterized by the presence of antibodies to desmoglein 1 and 3, which are adhesion molecules located between epidermal cells. Targeting these desmosomal antigens results in the loss of adhesion between keratinocytes, causing erosions and blisters, Dr. Mimouni explained.

SORRENTO, ITALY — Patients with pemphigus who are younger than 40 years at the time of diagnosis and whose first remission is brief are likely to have a more severe course of disease and multiple relapses, Dr. David Mimouni said at the Fifth International Congress on Autoimmunity.

Much remains unknown about the natural history of pemphigus. In an attempt to address this, a survey was undertaken of 155 patients diagnosed with some form of pemphigus and treated at an Israeli center between 1976 and 2004.

Follow-up for the patients ranged from 4 to 28 years. Of these patients, 94 were female. The age distribution at disease onset was typical of pemphigus, peaking between 40 and 50 years, said Dr. Mimouni of the department of dermatology, Rabin Medical Center, Petah Tiqwa, Israel.

Pemphigus vulgaris was the diagnosis in 144 patients. The remainder had diagnoses of pemphigus foliaceus, in which only the skin is involved and the mucous membranes are spared; pemphigus erythematosus, with features of both pemphigus and lupus; and paraneoplastic pemphigus.

In only 16 patients could a precipitating factor such as stress, drugs, or sun exposure be identified, he said.

The initial site of involvement was the mucosa alone in 50%, the skin alone in 47%, and both in 3%. At the time of follow-up, however, involvement limited to the mucosa or skin was seen only in 21% and 24%, respectively, while both sites were affected in 55%, Dr. Mimouni said.

A total of 91 patients were of Ashkenazi Jewish origin, while 58 were of Sephardic origin, and 6 were Arab. At the time of follow-up, the Sephardic patients were significantly less likely to be in remission than were the Ashkenazi, which was surprising, because a strong genetic link had previously been established for Ashkenazi origin, Dr. Mimouni said.

Younger patients and those whose initial remission lasted less than a year also were less likely to be in remission at the time of follow-up, as were those with mucosal involvement.

All patients had been treated with high doses of steroids, usually between 1.5 and 2 mg/kg per day, for periods up to 10 years. Most also had adjuvant therapy, most commonly with azathioprine, although recently other agents such as mycophenolate mofetil had been used.

Only 2% of the study patients had never had a relapse following treatment, while 40% had one to two relapses, and 58% had more than three, he said.

A total of 16 patients died. The causes of death were cancer, ischemic heart disease, and pulmonary embolism. None of the deaths was directly related to pemphigus, which represents a marked change from 1950, when 90% of patients would have died of pemphigus within 2 years, Dr. Mimouni said.

This study suggests that although there still is no cure for pemphigus, the morbidity and mortality associated with the disease have decreased significantly.

Progress has also been made in deciphering some of the underlying autoimmune processes in these conditions. For example, it is now known that pemphigus vulgaris is characterized by the presence of antibodies to desmoglein 1 and 3, which are adhesion molecules located between epidermal cells. Targeting these desmosomal antigens results in the loss of adhesion between keratinocytes, causing erosions and blisters, Dr. Mimouni explained.

SORRENTO, ITALY — Patients with pemphigus who are younger than 40 years at the time of diagnosis and whose first remission is brief are likely to have a more severe course of disease and multiple relapses, Dr. David Mimouni said at the Fifth International Congress on Autoimmunity.

Much remains unknown about the natural history of pemphigus. In an attempt to address this, a survey was undertaken of 155 patients diagnosed with some form of pemphigus and treated at an Israeli center between 1976 and 2004.

Follow-up for the patients ranged from 4 to 28 years. Of these patients, 94 were female. The age distribution at disease onset was typical of pemphigus, peaking between 40 and 50 years, said Dr. Mimouni of the department of dermatology, Rabin Medical Center, Petah Tiqwa, Israel.

Pemphigus vulgaris was the diagnosis in 144 patients. The remainder had diagnoses of pemphigus foliaceus, in which only the skin is involved and the mucous membranes are spared; pemphigus erythematosus, with features of both pemphigus and lupus; and paraneoplastic pemphigus.

In only 16 patients could a precipitating factor such as stress, drugs, or sun exposure be identified, he said.

The initial site of involvement was the mucosa alone in 50%, the skin alone in 47%, and both in 3%. At the time of follow-up, however, involvement limited to the mucosa or skin was seen only in 21% and 24%, respectively, while both sites were affected in 55%, Dr. Mimouni said.

A total of 91 patients were of Ashkenazi Jewish origin, while 58 were of Sephardic origin, and 6 were Arab. At the time of follow-up, the Sephardic patients were significantly less likely to be in remission than were the Ashkenazi, which was surprising, because a strong genetic link had previously been established for Ashkenazi origin, Dr. Mimouni said.

Younger patients and those whose initial remission lasted less than a year also were less likely to be in remission at the time of follow-up, as were those with mucosal involvement.

All patients had been treated with high doses of steroids, usually between 1.5 and 2 mg/kg per day, for periods up to 10 years. Most also had adjuvant therapy, most commonly with azathioprine, although recently other agents such as mycophenolate mofetil had been used.

Only 2% of the study patients had never had a relapse following treatment, while 40% had one to two relapses, and 58% had more than three, he said.

A total of 16 patients died. The causes of death were cancer, ischemic heart disease, and pulmonary embolism. None of the deaths was directly related to pemphigus, which represents a marked change from 1950, when 90% of patients would have died of pemphigus within 2 years, Dr. Mimouni said.

This study suggests that although there still is no cure for pemphigus, the morbidity and mortality associated with the disease have decreased significantly.

Progress has also been made in deciphering some of the underlying autoimmune processes in these conditions. For example, it is now known that pemphigus vulgaris is characterized by the presence of antibodies to desmoglein 1 and 3, which are adhesion molecules located between epidermal cells. Targeting these desmosomal antigens results in the loss of adhesion between keratinocytes, causing erosions and blisters, Dr. Mimouni explained.