It seems like every month, new clinical trial results are published that demonstrate the effectiveness of low dose naltrexone for a variety of dermatological conditions. While LDN is being studied for treating everything from cervical cancer to arthritis, the field where some of the most conclusive results are being found is dermatology. Research published this year has confirmed that low dose naltrexone is an effective treatment for psoriasis, erythromelalgia, and Hailey-Hailey disease.

Low Dose Naltrexone

Low dose naltrexone (LDN) is a lower dose of the FDA-approved drug naltrexone. Naltrexone was approved by the FDA for treating opioid addiction at a minimum dose of 50mg. At lower doses than 50mg (1mg-4.5mg) naltrexone is shown to have unique effects on the immune system. The theory is that LDN’s ability to modulate the immune system is the main reason it is so effective for a variety of dermatological conditions.

Psoriasis

In a study published in June this year of 71 patients with mild, moderate, and severe psoriasis the treatment was 6mg of low dose naltrexone given daily. These were the results from this study based on the PASI (Psoriasis Area and Severity Index) scores of patients. PASI measures the severity of psoriasis based on a range from 0 (no disease) to 72 (very severe disease).

Before Treatment:

After Treatment:

A summary of case reports published in March this year was based on the results of LDN treatment in 13 women and 2 men with psoriasis. Out of these patients, 5 had failed and 10 had only a partial response to previous treatments. The treatment results for 4.5mg LDN taken daily were:

• 8/15 marked improvement
• 2/15 somewhat improved
• 5/15 unchanged

These promising results show that LDN can improve psoriasis when patients do not respond to other treatments.

Erythromelalgia

Erythromelalgia is a rare arterial disease that results in swelling, redness, and pain throughout the body when temperature changes are experienced (usually temperatures above 84F). It most frequently presents in the hands and feet, and can be caused by environmental temperature changes or from consuming alcohol or spicy foods. The first course of action for patients diagnosed with this condition is to avoid the triggers that lead to a flare-up of symptoms. There is currently no standard treatment for erythromelalgia, however some case reports have demonstrated the effectiveness of LDN for this condition.

In a recently published case report, a 55-year old woman experienced erythomelalgia that was severe enough that it was painful for her to wear shoes. Several treatments were tried but had no effect, which included aspirin, nortriptyline, diltiazem, and topical nifedipine. It was found that gabapentin slightly reduced the pain but not completely. Mast cell-directed therapy was then initiated with ranitidine, famotidine, ketotifen, and loratadine. These treatments helped at first, but led to severe constipation.

The patient was then started on LDN, titrated up from 1mg per day up to 3mg per day. Since there was some improvement after 2 months, treatment was continued. After 11 months, the patient reported an improvement in pain, redness, and swelling in her feet. She continued taking LDN and at a 2-year follow-up, noted a significant clinical benefit and improvement in her quality of life.

It is believed that the ability of LDN to modulate the immune response is the main reason it may be effective for treating erythromelalgia and mast cell activation syndrome (MCAS). While EM is a relatively rare condition, it is believed that many patients may have MCAS and that it may be the cause of dermatologic symptoms for some patients.

Hailey-Hailey Disease

Hailey-Hailey disease (HHD) is a genetic skin condition that has a primary symptom of blistering and skin rashes. These often occur in the armpits, groin, neck, buttocks, and under the breasts. As with erythomelalgia, there is no specific treatment for Hailey-Hailey disease. The treatments available can help reduce symptoms and improve quality of life but there is no cure. Case studies have shown that LDN may be able to help reduce the symptoms of Hailey-Hailey disease.

In a study published in August this year, a patient with vulvar Hailey-Hailey disease was treated with low dose naltrexone. She was given 3mg of LDN daily, and after 5 months the lesions were no longer present.

In a separate case report, a man presented with HHD for which he had been receiving ongoing treatment for over 40 years.  He had never tried LDN, and was started on 1.5mg daily. Over the course of 2 months, the patient was increased to 3mg, 3 times daily. He achieved 95% improvement in his skin condition while taking low dose naltrexone. The patient continued to use LDN daily and maintained clearance of his disease.

Side Effect Profile of LDN

Low dose naltrexone has minimal side effects. The most common side effects reported are sleep disturbances and vivid dreaming. There may also be some gastrointestinal side effects as are possible with most orally administered medications. It is important also to remember that even though LDN was initially used for treating opioid addiction, it does not have any known abuse potential. Because of the low incidence of side effects associated with LDN it is often prescribed when patients can not use other treatments due to side effects or drug interactions.

Cost of LDN

Compared to most treatments for psoriasis, LDN is relatively inexpensive. Although insurance coverage may be limited, the out-of-pocket cost for the monthly treatment is reasonable for most patients. For patients without insurance coverage, LDN may be considered a first-line treatment option. Low dose naltrexone is obtained from compounding pharmacies as the low dosage required is not commercially available.

Continued Research

The initial clinical trials and case reports for low dose naltrexone in treating difficult-to-treat dermatological conditions are promising. For patients with chronic conditions that have been not been helped by other treatments, LDN may be a good option. It has a low side effect profile and the drug is FDA approved in higher doses. While larger trials are needed to better determine the effectiveness of LDN for specific conditions, it is clear that some patients are already benefiting from this potentially underutilized medication.