Small Fiber Neuropathy Underlies Erythromelalgia

PARK CITY, UTAH — Small fiber neuropathy plays an important role in erythromelalgia, a rare and mysterious skin condition characterized by red, hot, and painful extremities, Dr. Mark D.P. Davis said at a clinical dermatology seminar sponsored by Medicis.

Thermoregulatory sweat testing and other neurologic evaluations of 32 erythromelalgia patients showed that people with the syndrome do not sweat in all or part of their bodies, he reported.

Dr. Davis, dermatology professor at the Mayo Clinic in Rochester, Minn., illustrated his talk with diagrams of various patterns of impaired sweating, from the new study. These included regional and distal, multifocal, global, and distal areas where the patients did not sweat.

“Sweat glands are innervated by small nerves,” he explained. “If they are dysfunctional, you may not sweat normally.”

Recent papers documenting SCN9A mutations in an inherited form of erythromelalgia confirmed the neuropathic basis of the condition (J. Med. Genet. 2004;41:171–4 and J. Invest. Dermatol. 2005;124:1333–8). “Neurologists are now saying this is the prototype of a painful neuropathy,” he said.

Dr. Davis described nerves and the skin as “an underinvestigated area of dermatology that needs to be investigated” and suggested that the combination “may explain some of our unexplained conditions.”

The prevalence of neuropathy and vasculopathy in erythromelalgia suggests that “in other flushing conditions it is conceivable that the same thing is going on,” he said. He cited leprosy and brachioradial pruritus as infectious and itching skin disorders, respectively, that involve both nerves and skin.

The first description of erythromelalgia was published in 1878, Dr. Davis said. In 2000, he and his colleagues presented a natural history of the disorder based on 168 patients seen between 1970 and 1994 at the Mayo Clinic (Arch. Dermatol. 2000;136:330–6). None had other diagnoses to explain their symptoms. The patients' average age was 56 years, with a wide range of 5–91 years and average follow-up of 9 years. The majority, 72%, were female.

Two-thirds of the patients presented with abnormalities in the affected limb. These included redness (49%), acrocyanosis (10%), ulcers (6%), and reticular skin pattern (5%).

Half the patients were unable to walk long distances or stand for long periods. About 14% were unable to keep a job and 13% were unable to drive. Functional impairment was so debilitating that 3% required a wheelchair and 2% were bed-bound.

The investigators obtained Short-Form 36 Health Survey questionnaires from 98 patients. They scored poorly on all eight domains in the survey. The worst scores were for physical health and physical functioning.

All told, the patients had tried 84 different treatments with varying degrees of success. Nothing worked consistently, and the underlying cause of the condition remained elusive.

Dr. Davis cited several theories: excessive vasodilation causing high blood flow, increased local metabolism leading to hypoxia and tissue damage, and a platelet disorder with microvascular aspects.

In 2003, he and his colleagues offered a fourth, suggesting that erythromelalgia is associated with neuropathy and vasculopathy and possibly increased local cellular metabolism. They based their findings on 67 patients evaluated from 1999 through 2001 (Arch. Dermatol. 2003;139:1337–43).

Dr. Davis said that most patients in this study had neuropathy: Seventy-eight percent had small fiber neuropathy and 36% had abnormal electromyography studies. Among 57 patients for whom autonomic reflex screening was done, 49 (86%) had abnormalities. The most common abnormality was reduced or abnormal sweat production in sudomotor studies.

'Sweat glands are innervated by small nerves. If they are dysfunctional, you may not sweat normally.' DR. DAVIS

PARK CITY, UTAH — Small fiber neuropathy plays an important role in erythromelalgia, a rare and mysterious skin condition characterized by red, hot, and painful extremities, Dr. Mark D.P. Davis said at a clinical dermatology seminar sponsored by Medicis.

Thermoregulatory sweat testing and other neurologic evaluations of 32 erythromelalgia patients showed that people with the syndrome do not sweat in all or part of their bodies, he reported.

Dr. Davis, dermatology professor at the Mayo Clinic in Rochester, Minn., illustrated his talk with diagrams of various patterns of impaired sweating, from the new study. These included regional and distal, multifocal, global, and distal areas where the patients did not sweat.

“Sweat glands are innervated by small nerves,” he explained. “If they are dysfunctional, you may not sweat normally.”

Recent papers documenting SCN9A mutations in an inherited form of erythromelalgia confirmed the neuropathic basis of the condition (J. Med. Genet. 2004;41:171–4 and J. Invest. Dermatol. 2005;124:1333–8). “Neurologists are now saying this is the prototype of a painful neuropathy,” he said.

Dr. Davis described nerves and the skin as “an underinvestigated area of dermatology that needs to be investigated” and suggested that the combination “may explain some of our unexplained conditions.”

The prevalence of neuropathy and vasculopathy in erythromelalgia suggests that “in other flushing conditions it is conceivable that the same thing is going on,” he said. He cited leprosy and brachioradial pruritus as infectious and itching skin disorders, respectively, that involve both nerves and skin.

The first description of erythromelalgia was published in 1878, Dr. Davis said. In 2000, he and his colleagues presented a natural history of the disorder based on 168 patients seen between 1970 and 1994 at the Mayo Clinic (Arch. Dermatol. 2000;136:330–6). None had other diagnoses to explain their symptoms. The patients' average age was 56 years, with a wide range of 5–91 years and average follow-up of 9 years. The majority, 72%, were female.

Two-thirds of the patients presented with abnormalities in the affected limb. These included redness (49%), acrocyanosis (10%), ulcers (6%), and reticular skin pattern (5%).

Half the patients were unable to walk long distances or stand for long periods. About 14% were unable to keep a job and 13% were unable to drive. Functional impairment was so debilitating that 3% required a wheelchair and 2% were bed-bound.

The investigators obtained Short-Form 36 Health Survey questionnaires from 98 patients. They scored poorly on all eight domains in the survey. The worst scores were for physical health and physical functioning.

All told, the patients had tried 84 different treatments with varying degrees of success. Nothing worked consistently, and the underlying cause of the condition remained elusive.

Dr. Davis cited several theories: excessive vasodilation causing high blood flow, increased local metabolism leading to hypoxia and tissue damage, and a platelet disorder with microvascular aspects.

In 2003, he and his colleagues offered a fourth, suggesting that erythromelalgia is associated with neuropathy and vasculopathy and possibly increased local cellular metabolism. They based their findings on 67 patients evaluated from 1999 through 2001 (Arch. Dermatol. 2003;139:1337–43).

Dr. Davis said that most patients in this study had neuropathy: Seventy-eight percent had small fiber neuropathy and 36% had abnormal electromyography studies. Among 57 patients for whom autonomic reflex screening was done, 49 (86%) had abnormalities. The most common abnormality was reduced or abnormal sweat production in sudomotor studies.

'Sweat glands are innervated by small nerves. If they are dysfunctional, you may not sweat normally.' DR. DAVIS

PARK CITY, UTAH — Small fiber neuropathy plays an important role in erythromelalgia, a rare and mysterious skin condition characterized by red, hot, and painful extremities, Dr. Mark D.P. Davis said at a clinical dermatology seminar sponsored by Medicis.

Thermoregulatory sweat testing and other neurologic evaluations of 32 erythromelalgia patients showed that people with the syndrome do not sweat in all or part of their bodies, he reported.

Dr. Davis, dermatology professor at the Mayo Clinic in Rochester, Minn., illustrated his talk with diagrams of various patterns of impaired sweating, from the new study. These included regional and distal, multifocal, global, and distal areas where the patients did not sweat.

“Sweat glands are innervated by small nerves,” he explained. “If they are dysfunctional, you may not sweat normally.”

Recent papers documenting SCN9A mutations in an inherited form of erythromelalgia confirmed the neuropathic basis of the condition (J. Med. Genet. 2004;41:171–4 and J. Invest. Dermatol. 2005;124:1333–8). “Neurologists are now saying this is the prototype of a painful neuropathy,” he said.

Dr. Davis described nerves and the skin as “an underinvestigated area of dermatology that needs to be investigated” and suggested that the combination “may explain some of our unexplained conditions.”

The prevalence of neuropathy and vasculopathy in erythromelalgia suggests that “in other flushing conditions it is conceivable that the same thing is going on,” he said. He cited leprosy and brachioradial pruritus as infectious and itching skin disorders, respectively, that involve both nerves and skin.

The first description of erythromelalgia was published in 1878, Dr. Davis said. In 2000, he and his colleagues presented a natural history of the disorder based on 168 patients seen between 1970 and 1994 at the Mayo Clinic (Arch. Dermatol. 2000;136:330–6). None had other diagnoses to explain their symptoms. The patients' average age was 56 years, with a wide range of 5–91 years and average follow-up of 9 years. The majority, 72%, were female.

Two-thirds of the patients presented with abnormalities in the affected limb. These included redness (49%), acrocyanosis (10%), ulcers (6%), and reticular skin pattern (5%).

Half the patients were unable to walk long distances or stand for long periods. About 14% were unable to keep a job and 13% were unable to drive. Functional impairment was so debilitating that 3% required a wheelchair and 2% were bed-bound.

The investigators obtained Short-Form 36 Health Survey questionnaires from 98 patients. They scored poorly on all eight domains in the survey. The worst scores were for physical health and physical functioning.

All told, the patients had tried 84 different treatments with varying degrees of success. Nothing worked consistently, and the underlying cause of the condition remained elusive.

Dr. Davis cited several theories: excessive vasodilation causing high blood flow, increased local metabolism leading to hypoxia and tissue damage, and a platelet disorder with microvascular aspects.

In 2003, he and his colleagues offered a fourth, suggesting that erythromelalgia is associated with neuropathy and vasculopathy and possibly increased local cellular metabolism. They based their findings on 67 patients evaluated from 1999 through 2001 (Arch. Dermatol. 2003;139:1337–43).

Dr. Davis said that most patients in this study had neuropathy: Seventy-eight percent had small fiber neuropathy and 36% had abnormal electromyography studies. Among 57 patients for whom autonomic reflex screening was done, 49 (86%) had abnormalities. The most common abnormality was reduced or abnormal sweat production in sudomotor studies.

'Sweat glands are innervated by small nerves. If they are dysfunctional, you may not sweat normally.' DR. DAVIS