Acrodynia

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Background

Now a rare disease, acrodynia (painful extremities) primarily affects young children. The symptoms of irritability, photophobia, pink discoloration of the hands and feet, and polyneuritis can be attributed to chronic exposure to mercury.[1, 2, 3] Also see Mercury Toxicity.

Pathophysiology

The most frequent sources of mercury prior to the legislated removal of the heavy metal from these preparations were calomel-containing anthelminthics, laxatives, diaper rinses, teething powders, fungicides in paint, repeated gamma-globulin injections, termite-protected wood (mercury bichloride), watch batteries (ie, via ingestion), mercurial antibacterial ointments, mercurial skin-lightening creams,[4]  and dental amalgam. This legislation corresponded to the virtual disappearance of acrodynia. Present-day cases reveal more novel exposure, such as mercuric oxide used to treat eyelid mites. Some have suggested the disease may represent a delayed allergic or hypersensitivity reaction because not all persons exposed to mercurial compounds develop the disease.

Because the metal can be stored in the body to some extent and intolerance may develop long after exposure, morbid symptoms may appear weeks or months after the drug administration (ie, exposure), with its cause escaping recognition. The deleterious effects of relatively small doses of mercury on the nervous system that are sometimes seen in the course of acrodynia add to the acrodynic reaction. In acrodynia, no reflex dilatation of the peripheral vessels occurs in response to heat. Vasoconstriction is abolished only when the nerve supply to the arterioles is interrupted.

Etiology

Mercury exposure in a sensitive person is considered to be responsible for the development of acrodynia. A genetic predisposition is possible.

Epidemiology

Frequency

United States

Acrodynia was once widely prevalent; however, it is rare today, owing to the discontinued use of mercury in different preparations.

International

Acrodynia was especially common in Australia. Epidemics of mercury poisoning have followed the release of mercury into the environment from industrial activity,[5, 6, 7] with uptake of methyl mercury from eating fish from Minamata Bay, Japan, and uptake of both inorganic and methyl mercury following the release of mercury vapor and its subsequent deposition in waterways from gold recovery procedures in the Amazon basin.[8] The ingestion of wheat and barley seed treated with an alkyl mercury fungicide for sowing, by a largely illiterate population in Iraq, led to a major outbreak of poisoning with a high fatality rate.

Age

Acrodynia most often occurs in infants and young children. The age of onset is between 4 months and 8 years. Newborns and adults appear to be less susceptible to the disease.

Prognosis

Symptoms gradually disappear as insidiously as they began. Recovery is complete in the vast majority of patients. Older children tend to have less morbidity. Death can result in 10% of cases.

Patient Education

For patient education resources, visit the Oral Health Center. Also, see the patient education article Teething.

History

Children initially become listless, drowsy, and irritable, with a tendency to cry. Anorexia and subsequent weight loss can occur. More than 50% of patients demonstrate photophobia. Hypotonia, the ability to hyperextend or overextend the limbs, and atrophy of muscles are noted. The child may refuse to walk.

Physical Examination

The initial symptoms are followed by the numerous cutaneous manifestations in 2-4 weeks. The skin changes are characteristic. The review by Dinehart et al from 1988 is notable.[9]  Early in the course of the disease, the tip of the nose, fingers, and toes acquire a pinkish color, which subsequently develops into a reticulate erythema of deeper hue.[10]

The hands and feet become painful, cold, cyanotic, erythematous, and swollen. Erythema is usually blotchy but may be diffuse. Hemorrhagic puncta are also noted. On the trunk, the erythema is blotchy and may be macular or papular. Extreme pain and pruritus in the extremity often leads to lichenified, excoriated changes as the child constantly rubs and scratches his or her skin. Patients may assume the "salaam position" in which they sit with their heads between their legs and rub their hands together.

Inflammation, swelling, and focal gum erosion can been seen with subsequent loss of teeth. These changes are early.

A notable symptom is massive hyperhidrosis with a mouselike smell, which may lead rapidly to miliaria rubra. This can easily turn to bacterial secondary infection with a tendency for ulcerating pyoderma.

Persistent hypertension, tachycardia, susceptibility to bronchitis, dyspepsia, precipitant micturition, salivation, and hypotonia can be observed. Usually, the patient develops a moderate upper respiratory tract infection with a sore throat.[11]

Alopecia has been noted. Nail loss has also been reported.

Complications

Long-term disability has been noted. Some patients have been shown to have lower intelligence test scores and abnormal electroencephalographic tracings, indicating possible organic damage to the CNS.

Laboratory Studies

Evidence of excess mercury in the urine of affected persons has been noted. A 24-hour urine collection is recommended because urinary elimination of mercury is unpredictable and may vary from day to day or from hour to hour. Mercury values in persons with acrodynia can vary from 0-401 mcg/L. A value of less than 10 mcg/L is generally considered within reference range. Concentrations greater than 300 mcg/L are considered the threshold of toxicity, and symptoms rarely occur until mercury excretion rises to this level.

Blood evaluation is recommended, particularly for acute intoxication. Normal levels rarely exceed 15 mcg/L. Mercury levels in the plasma may be elevated for prolonged periods because of slow release from erythrocytes after oxidation.

Mercury blocks the action of catechol methyl transferase, leading to increased amounts of vanillylmandelic and homovanillic acid in urine.

Excretion of 17-ketosteroid has also been shown to be increased in these patients.

Analysis of hair strands by means of x-ray fluorescence for mercury contamination also may be considered, but the results may be falsely elevated in persons residing in environments with increased ambient atmospheric concentrations or in populations consuming methylmercury-contaminated seafood.

Histologic Findings

Hyperplastic sweat glands and nonspecific inflammation have been observed in skin biopsy specimens. Degenerative changes have been found in peripheral nerves and chromatolytic changes at the anterior horn cells of the spinal cord.

Medical Care

Removal of the inciting agent is the goal of treatment. Correcting fluid and electrolyte losses and rectifying any nutritional imbalances (vitamin-rich diets, vitamin-B complex) are of utmost importance in the treatment of the disease.

The chelating agent meso 2,3-dimercaptosuccinic acid has been shown to be the preferred treatment modality.[17] It can almost completely prevent methylmercury uptake by erythrocytes and hepatocytes.

In the past, dimercaprol (British antilewisite; 2,3-dimer-capto-l-propanol) and D-penicillamine were the most popular treatment modalities. Disodium edetate (Versene) was also used. Neither disodium edetate nor British antilewisite has proven reliable. British antilewisite has now been shown to increase CNS levels and exacerbate toxicity. N -acetyl-penicillamine has been successfully given to patients with mercury-induced neuropathies and chronic toxicity, although it is not approved for such uses. It has a less favorable adverse effect profile than meso 2,3-dimercaptosuccinic acid.[18]

Hemodialysis with and without the addition of L-cysteine as a chelating agent has been used in some patients experiencing acute renal failure from mercury toxicity.

Peritoneal dialysis and plasma exchange also may be of benefit.

Tolazoline (Priscoline) has been shown to offer symptomatic relief from sympathetic overactivity.

Antibiotics are necessary when massive hyperhidrosis, which may rapidly lead to miliaria rubra, is present. This can easily progress to bacterial secondary infection with a tendency for ulcerating pyoderma.

Medication Summary

The goals of pharmacotherapy are to remove the causing agent, to reduce morbidity, and to prevent complications.

Succimer (Chemet)

Clinical Context:  Succimer is a metal chelating agent, an analog of dimercaprol, and is used in lead poisoning. It is available as 100-mg capsule.

Class Summary

Succimer almost completely prevents methylmercury uptake by erythrocytes and hepatocytes.

Author

Kamila K Padlewska, MD, PhD, Professor, Warsaw Academy of Cosmetics and Health Care; Chief Executive, Cosmetic-Medical Cooperative Izis, Poland

Disclosure: Nothing to disclose.

Coauthor(s)

Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School

Disclosure: Nothing to disclose.

Specialty Editors

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Disclosure: Nothing to disclose.

Jeffrey J Miller, MD, Associate Professor of Dermatology, Pennsylvania State University College of Medicine; Staff Dermatologist, Pennsylvania State Milton S Hershey Medical Center

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Shyam Verma, MBBS, DVD, FAAD, Clinical Associate Professor, Department of Dermatology, University of Virginia School of Medicine; Adjunct Associate Professor, Department of Dermatology, State University of New York at Stonybrook School of Medicine; Adjunct Associate Professor, Department of Dermatology, University of Pennsylvania School of Medicine

Disclosure: Nothing to disclose.

References

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