Research

PURPOSE OF REVIEW: The purpose of this review is to evaluate and explain our current understanding of the clinical use of low-dose naltrexone in the treatment of chronic pain. RECENT FINDINGS: Recent pre-clinical uses and clinical studies further elucidate the use of low-dose naltrexone in the treatment of chronic pain. Low-dose naltrexone (LDN) has shown promise to reduce symptoms related to chronic pain conditions such as fibromyalgia, inflammatory bowel conditions, and multiple sclerosis. The mechanism of LDN appears to be modulation of neuro-inflammation, specifically, the modulation of the glial cells and release of inflammatory chemicals in the central nervous system. These effects appear to unique at low dosage compared to dosage for food and drug administration approved use for alcohol and opioid dependence. We review the evidence that LDN has shown more than promise and should be further investigated in clinical practice.

PURPOSE: To report a case of vulvar familial benign pemphigus, or Hailey-Hailey disease, treated successfully with low-dose naltrexone and to review the current literature.

METHODS: We report a case of a 71-year-old white woman with vulvar Hailey-Hailey disease recalcitrant to topical corticosteroids. After treatment with low-dose naltrexone, 3 mg nightly was initiated, the lesions began to heal and 5 months later her skin showed no lesions. A literature review on the use of low-dose naltrexone for Hailey-Hailey disease was performed. We searched the PubMed/MEDLINE databases for previous case reports using the key words ''Pemphigus, Benign Familial'' and ''naltrexone"". RESULTS: We found 35 more cases of Hailey-Hailey disease treated with naltrexone, showing promising results, reported until January 2020, with no major adverse effects.

CONCLUSION: Low-dose naltrexone may represent a cost-effective and successful treatment modality in nongeneralized Hailey-Hailey disease without serious adverse effects. Future prospective studies are needed to investigate this interesting therapeutic option.

Sjogren's syndrome (SS) is a chronic autoimmune disorder that causes the inflammation of the lacrimal and salivary glands, resulting in dryness of the eyes and mouth. In addition, fatigue and musculoskeletal pain, often described as aching, are very common. Treatment directed towards alleviating the fatigue and pain associated with SS is currently very limited. In March of 2019, the first peer reviewed case report showing clinical improvement using low-dose naltrexone (LDN) in a patient with suspected SS was published in Cureus. This report describes two additional patients with SS whose conditions responded favorably to a treatment with LDN therapy. The first case is a 24-year-old female with documented SS. Her diagnosis was based on a history of dry eyes, dry mouth, joint pain, fatigue, and headache. In addition, she had very high measures of inflammation and a positive anti SS-A antibody. She improved clinically with LDN therapy. The second case is a 66-year-old female with documented SS based on a history of dry eyes and dry mouth, joint pain, and elevated anti-SSA and anti-SSB antibodies whose joint symptoms responded to treatment with LDN.

OBJECTIVE: To determine the efficacy of low dose naltrexone in the patients of psoriasis. Study design: Non-randomised clinical trial. Place and duration of study: Department of Dermatology, Jinnah Postgraduate Medical Centre, Karachi from January to July 2019.

METHODOLOGY: All patients of mild, moderate, and severe psoriasis with age above 13 years without any comorbids were included in this study. Patients were started on tablet naltrexone 6mg daily after assessing PASI, BSA and DLQI scores and were called every month for follow-up. After three months of treatment, these scores were assessed again. SPSS 23 was used to analyse the data.

RESULTS: Out of 71 patients, 37 (52%) were males and 34 (48%) were females with age ranging from 13 to 60 years with mean age of 37.85 ±12.211 years. The mean duration of disease was 5.27 ±3.084 years. Before treatment 1 (1.4%), 20 (28.2%), 24 (33.8%), 26 (36.6%) patients had mild, moderate, severe and very severe psoriasis according to PASI score. After treatment, 14 (19.7 %), 23 (32.4%), 23 (32.4%), 11 (15.5%) patients had mild, moderate, severe and very severe psoriasis. The mean PASI, BSA and DLQI were 18.47 ±8.157, 11.97 ±3.873 and 22.63 ±5.235 before treatment, respectively. The mean PASI, BSA and DLQI were 13.51 ±8.017, 8.07 ±3.650 and 16.31 ±7.056 after treatment, respectively.

CONCLUSION: Low dose naltrexone is an effective therapy for psoriasis as in other chronic dermatological diseases. It is a cost-effective therapy with few tolerable side-effects. It requires further studies for long-term response. Key Words: Naltrexone, Psoriasis, PASI, DLQI, BSA.

PURPOSE: Neuropathic corneal pain (NCP) is a recently described ocular pain modality resulting from nerve damage and presenting with symptoms of pain or persistent unpleasant sensations, such as dryness, burning, or light sensitivity. When symptoms do not resolve with topical anesthetics, this point to a non-ocular source of pain. Low-dose naltrexone (LDN) acts as a neuromodulator with a neuroprotective effect via inhibition of microglial activation in the central nervous system and upregulation of endogenous opioid production. We aimed to assess the efficacy and tolerability of LDN for NCP.

METHODS: In a retrospective cohort study,patients diagnosed with ocular pain and the keyword “naltrexone” were identified. All patients were required to have been diagnosed with NCP and using LDN for at least 3 months. Diagnosis was based on medical history, discordance in clinical signs and symptoms, and corneal in vivo confocal microscopic findings. Patients were required to exhibit persistent ocular discomfort/pain after instillation of 0.5% proparacaine hydrochloride. Patients were excluded if they had any ocular pathology that might cause pain.

RESULTS: Thirty out of 71 identified patients were included in the final data-set based on inclusion/exclusion criteria. Mean age was 45.60±19.30 years with a white (80.00%) female (73.33%) predominance. Time between visits (duration of LDN use) was 14.87±11.25 months (range 1-36 months) and duration of NCP prior to treatment was 17.53±17.29 months (range 3-79 months). The average percent improvement was -49.22%. Sixteen patients (53.33%) had equal to or more than 50% improvement, 4 patients (13.33%) had 30-49% improvement, 5 patients (16.67%) had 1-29% improvement, and 5 patients (16.67%) did not improve. Mean Quality of life (QoL) score by the ocular pain assessment survey was 5.84±2.57 (range 1.14-9.00) at the first visit (p<0.0001). Mean QoL score improved to 3.77±2.91 (range 0-8.86) at the last visit (p=0.023). Pre-treatment comorbidities were dry eye disease (66.67%), neuropsychiatric diseases (30.61%) and auto-immune diseases (10.20%). All patients were on previous systemic medications (most common being Nortriptyline 26.7% and SSRI 16.7%).

CONCLUSIONS: LDN was effective and well tolerated as an adjunct therapy for NCP.

Hailey-Hailey disease (HHD) is an uncommon autosomal dominant disorder resulting from a mutation in the ATP2C1 gene resulting in dysfunction of the Golgi apparatus calcium-associated ATPase, thus interfering with intercellular calcium signaling.

HHD presents clinically as flaccid blisters and erosions in intertriginous areas, especially the axillae and groin. The major histologic finding is acantholysis throughout the spinous layer of the epidermis, commonly referred to as a “dilapidated brick wall” appearance. The initial lesions and associated symptoms usually develop during the second or third decade of life. Complications of HHD include infections (bacterial, fungal, and viral), and malignant transformation (cutaneous squamous cell carcinoma). A 56-year-old female presented to clinic with a worsening rash located on her upper arms, inguinal region, and lower back. Physical exam revealed erythematous, macerated, crusted plaques located on the upper arm, inguinal region, and lower back. The erosions had a “worm-eaten” pattern. Shave biopsy was performed on lesions revealing widespread acantholysis of the epidermis and minimal dyskeratosis. Over the course of several months, the patient was treated with multiple therapies including high potency topical corticosteroids, oral therapy with doxycycline, and two intramuscular injections of 40 mg/ml triamcinolone acetonide. Due to the progressively worsening and recalcitrant nature of the disease, the patient was started on 3 mg/day of oral naltrexone. After 3 months of treatment on 3 mg daily of naltrexone, the patient had almost complete resolution of active lesions on her upper arms, inguinal region, and lower back. The remaining skin changes represent post-inflammatory hyperpigmentation.

BACKGROUND: Lichen planopilaris (LPP) is one of the important causes of cicatricial alopecia. We aimed to evaluate the efficacy and safety of low-dose naltrexone (LDN) in the setting of a clinical trial in patients with LPP.

METHODS: We included patients with LPP between 2018 and 2020. Patients were allocated to two groups. The first group received topical clobetasol plus oral low dose naltrexone (3mg) while the second received topical clobetasol plus placebo. The assessment was made for the disease severity by lichen planopilaris activity index (LPPAI) instrument and the safety of the drug in 2-month intervals up to 6 months. To compare both groups, we used the ANOVA test for repeated measures.

RESULTS: Thirty-four patients were analyzed in intention-to-treat fashion. There was a decrescendo pattern on LPPAI scores that was statistically significant within the LDN (P = 0.001) but almost significant within the placebo group (P = 0.060) and non-significant between the groups (P = 0.813). The side effects attributable to the low dose naltrexone was not statistically different between studied groups.

CONCLUSION: Low dose naltrexone (3mg) failed to improve the severity of the LPP more than what is achievable with topical clobetasol.

Safe, inexpensive, and convenient psoriasis therapy is desirable. Two recent case reports suggested that low-dose naltrexone is effective. Cases from our practice are presented in order to further the evidence of efficacy and safety of low-dose naltrexone in the treatment of psoriasis. Patients included 13 females, 2 males; mean age 57 years; mean psoriasis duration 16 years. Of the patients, 8 had psoriatic arthritis. In the past, 5 had completely failed and 10 had partially responded to =1 topical therapies. Patients used a self-assessed Likert scale on the effect of low-dose naltrexone on their psoriasis: 1 - worse; 2 - unchanged; 3 - slightly improved; 4 - somewhat improved; 5 - marked improvement. The response to 4.5 mg of oral naltrexone was as follows: 8/15 marked improvement; 2/15 somewhat improved; and 5/15 unchanged. Three adverse events included insomnia, diarrhea, and self-limited headache. Marked improvement was seen by 53% of the 15 patients. Low-dose naltrexone regulates lymphocyte responses, reduces cytokine production, and likely reduces mast cell activity. Low-dose naltrexone is safe, inexpensive, and appears be effective in this open-label study.

Pharmacist Dr. Loyd V. Allen, Jr. reviews methods of preparation, uses, packaging, labeling, stability, and quality control of 1.5mg and 4.5mg capsules of low dose naltrexone. An interesting and unexpected effect of naltrexone is its action in pain relief for different disorders. A notable aspect of naltrexone use in pain patients is that the dose is only about one-tenth of the normal dose. Since naltrexone HCl is available in 50-mg tablets, low-dose naltrexone must be compounded for patients.