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Eosinophilia-Myalgia Syndrome - An Epidemic Borne From Capitalism

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Eosinophilia-myalgia syndrome is a systemic immune-mediated disorder resulting from ingesting a particular synthetic amino acid. Read the article to know more.

Medically reviewed by

Dr. Muntaqa Butt

Published At January 3, 2023
Reviewed AtOctober 20, 2023

Introduction

Eosinophilia-myalgia syndrome (EMS) is a rare systemic immune-mediated disorder that induced an epidemic in the United States during the late 80s due to ingestion of a highly popular and openly available health food supplement amino acid like L-tryptophan. This led to a complete ban and recall of the product in March 1990 by the Food and Drug Administration (FDA). This restriction lasted until 2005, when L-tryptophan returned to the market.

Who Is Susceptible to Eosinophilia-Myalgia Syndrome?

As per an estimate, nearly 5,000-10,000 individuals developed symptoms during the 1989 epidemic in the United States over six months. As per June 1993 reports, 1511 cases have been reported, out of which about 35 percent required hospitalization causing 37 deaths. About 84 percent of the population were females, and 97 percent were from non-Hispanic people. 86 percent of the population were above the age of 34, with a median age of 49. Almost all (over 98 percent) reported cases during the epidemic had consumed products from a single manufacturer. Similar cases were reported in Spain, the United Kingdom, Germany, and Canada.

What Causes Eosinophilia-Myalgia Syndrome?

The eosinophilia-myalgia syndrome epidemic was caused by ingesting an L-tryptophan amino acid supplement manufactured by a single Japanese pharmaceutical company. The condition is attributed to L-tryptophan or 5-HTP (5-hydroxytryptophan) dietary supplements. 5-HTP is still being used as an L-tryptophan alternative. These supplements were used in body-building products, weight loss supplements, and sleep aids.

These synthetic amino acid supplements are produced by pharmaceutical companies with the help of genetically engineered bacteria. In December 1988, the manufacturer introduced a new strain of bacteria with a higher amino-acid yield. The bacterium is grown in vats and then goes through a series of filtration, crystallization, and separation steps. The purification procedure included the usage of activated carbon powder.

When the manufacturer started using the new strain, they reduced the quantity of activated carbon powder used for purification. Some of the fermentation batches manufactured between October 1988 and June 1989 skipped the filtration process, producing lower-grade amino acids. The triad of the new strain, along with decreased activated carbon and lower-grade products, led to the epidemic of 1989.

How Does L-Tryptophan Affect the Body?

L-tryptophan gets converted into serotonin in the body. 5-HTP is also involved in the same metabolic pathway. Serotonin plays a crucial role in mood regulation, sleep cycle, digestion, nausea, wound healing, bone health, blood clotting, and sexual desire. Hence, the supplements were readily available to the general population having related complaints.

What Happened During the 1989 Epidemic?

  • The first case appeared in October 1989 when three women who consumed L-tryptophan supplements presented with eosinophilia and myalgia. These findings were locally published. Thereafter, similar cases got reported all over the United States and several other countries.

  • Health departments conducted epidemiological studies within a few days, and by November, state health departments in New Mexico and Minnesota suspected a close association between L-tryptophan consumption and EMS.

  • CDC conducted national surveillance, and by November 11th, FDA issued a nationwide siren warning consumers against consuming the said supplement. The product was ordered to be recalled and removed from the shelves.

  • The number of cases sharply declined after the recall but not before the death of 37 patients. In most cases, patients were affected in the prime of their lives and developed deliberating diseases. The alertness of physicians and prompt responses by the CDC and FDA resulted in identifying the link between EMS and tryptophan-containing supplements.

  • In 1994, Congress passed the Dietary Health Supplement Education Act (DHSEA), which greatly capped FDA’s control over supplements, due to which L-tryptophan-containing supplements legally returned to the shelves.

  • Isolated EMS cases were reported before the epidemic and after the ban. The pre-pandemic cases were attributed to L-tryptophan, but 5-HTP supplements were the causality of EMS during the ban since 5-HTP is involved in the metabolism of L-tryptophan to serotonin.

  • For the past several years, the National Eosinophilia Myalgia Syndrome Network (NEMSN) has reported many cases involving L-tryptophan and 5-HTP-containing supplements.

What Are the Signs and Symptoms of Eosinophilia-Myalgia Syndrome?

The signs and symptoms of EMS are categorized into initial and later symptoms.

The initial symptoms include:

  • Acute pain.

  • Elevated eosinophil count (over 1000 cells/mm3).

  • Severe myalgias (muscle cramps and pain).

  • Myofascial pain syndrome (chronic muscle pain).

  • Neuropathy (numbness, weakness, burning pain, and loss of reflexes).

  • Neurologic pain in joints.

  • Tremor.

  • Peripheral edema.

  • Paresthesias (numbness, tingling, or burning sensation).

  • Fasciitis (inflammation of the fascia).

  • Morphia (yellow or ivory-colored dry skin).

  • Low-grade fever.

  • Pulmonary disorders.

  • Rashes.

  • Weakness.

  • Fatigue.

  • Gastrointestinal disorders.

  • Cardiac arrhythmias.

  • Hair loss.

  • Dyspnea or cough.

  • Headache.

The later symptoms include:

  • Neurocognitive deficits (short-term memory loss, concentration, and communication problems).

  • Chronic myalgias and arthralgias (long-standing muscle and joint pains).

  • Severe axonal neuropathies (pain along a nerve cell).

  • Cardiomyopathy.

  • Liver cirrhosis.

  • Internal fibrosis of the bone.

  • Pulmonary hypertension.

  • A desmoid tumor (benign soft tissue tumors).

  • Malignant fibrous histiocytoma (autoimmune disorder by the histiocytes).

  • Scleroderma-like syndrome (skin disease with features similar to scleroderma).

  • Fibromyalgia syndrome (musculoskeletal pain and fatigue with sleep, memory, and mood issues).

  • Chronic fatigue syndrome.

  • Post-traumatic stress disorder.

  • Depression.

  • Visual and dental problems.

  • Sleeping disorders.

How to Diagnose Eosinophilia-Myalgia Syndrome?

EMS diagnosis depends on the physician’s observation and examination, as no serological tests are available for confirmatory diagnosis. The diagnosis criteria, as defined by the CDC in the wake of the 1989 pandemic, include the following:

  • Eosinophil count from a peripheral blood draw of above 1000 cells/mm3.

  • Severe muscle pain.

  • No other infection explains the presenting myalgia or eosinophilia.

Toxic oil syndrome is a rare systemic disorder that provoked an epidemic in Spain during the early 1980s. The condition was caused due to ingestion of rapeseed oil, intended for industrial use, fraudulently sold as olive oil. The consumers developed symptoms like dyspnea, cough, chest pain, headaches, fever, abdominal pain, dysphagia, nausea, skin rash, itching, tachycardia, hepatomegaly, splenomegaly, severe muscle pain, cramps, abnormally high levels of eosinophils.

According to a finding, the contaminant 3-phenyl amino-1,2-propanediol in the oil was chemically similar to phenylamino alanine (contaminant in L-tryptophan). The similarity in symptoms and chemical composition of the contaminants led to a probable hypothesis that there might be a similarity in the final pathway of neuromuscular damage seen in both conditions.

How to Treat or Manage Eosinophilia-Myalgia Syndrome?

EMS symptom presentation is varied and diverse; hence a universal treatment protocol has not been established. Patients are prescribed symptomatic medication according to their specific manifestations. Muscle relaxants, analgesics, diuretics, and high doses of Corticosteroids (to reduce inflammation) are prescribed.

In the acute stages, patients are advised to reduce physical strain to avoid muscle cramps and myalgias. In chronic stages, individuals who practice regular physical activities tend to do better.

What Is the Prognosis of Eosinophilia-Myalgia Syndrome?

Most patients with EMS continue to live with the symptoms for three to four years after initiation of treatment. The severity of the condition depends on the quantity of supplements ingested prior to diagnosis. There tends to be severe muscle damage, causing lingering muscle spasms, pain, and fatigue. Patients with severe symptoms during the acute phase tend to have a poor diagnosis.

What Is the Differential Diagnosis of Eosinophilia-Myalgia Syndrome?

  • Toxic-oil syndrome.

  • Fibromyalgia.

  • Chronic fatigue syndrome.

  • Lupus (the body’s defense system attacks its own cells).

  • Arthritis (joint pain and swelling).

  • Eosinophilic fasciitis (inflammation of tissue under the skin).

  • Churg-Strauss syndrome (disease associated with blood vessel inflammation).

  • Hypereosinophilic syndrome (persistently high eosinophils-type of white blood cell).

  • Eosinophilic cellulitis (inflammatory skin disorder of unknown origin).

  • Scleroderma (an autoimmune disorder that causes the hardening of connective tissues).

What Are the Complications of Eosinophilia-Myalgia Syndrome?

Untreated EMS can progress to several neuropathies, organ damage, fasciitis (fascia inflammation), gangrene (dead tissue), and, ultimately, death.

Conclusion

EMS is a condition borne out of negligence, but even after decades, the situation has not improved in the unregulated supplement industry. FDA currently has a limited say in the manufacture and distribution of supplements which has led to a manifold increase in unregulated and untested supplements flooding the market. Recently a similar adulteration in two popular protein-building supplements with ‘aegeline,’ which was not reported to the FDA, resulted in non-infectious acute hepatitis and liver failure. The FDA issued warnings to the manufacturer, and the Department of Justice brought criminal charges on all manufacturers that used the unreported product, which seems too little and too late.

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Dr. Muntaqa Butt
Dr. Muntaqa Butt

General Practitioner

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