Conflict of interest: No disclosure of interest.
Itch in familial lichen amyloidosis: effective treatment with amitriptyline in two cases
Article first published online: 25 MAR 2013
© 2013 Wiley Periodicals, Inc.
Volume 27, Issue 1, pages 12–15, January/February 2014
How to Cite
Yew, Y. W. and Tey, H. L. (2014), Itch in familial lichen amyloidosis: effective treatment with amitriptyline in two cases. Dermatologic Therapy, 27: 12–15. doi: 10.1111/dth.12023
- Issue published online: 6 FEB 2014
- Article first published online: 25 MAR 2013
- primary localized cutaneous amyloidosis
Itch is a characteristic feature of lichen amyloidosis and the symptom can be debilitating. Treatments, however, are generally not effective. We report amitriptyline as a novel therapy in treating itch in two patients with familial lichen amyloidosis who did not respond to prior potent topical corticosteroids and antihistamines. Outcomes of treatment were assessed using the itch score on a visual analog scale, itch frequency, and the Dermatology Life Quality Index (DLQI). After taking amitriptyline 10 mg o.n. for 6 weeks, the itch score of one patient was reduced from 8.5 to 2 of 10, whereas the second patient's itch score was reduced from 5 to 1. In the latter, his DLQI concurrently reduced from 14 to 6 of 30. Pathophysiology of itch in lichen amyloidosis may involve both cutaneous and neural components and amitriptyline is known to be useful for neuropathic itch. Low-dose amitriptyline poses little risk of side effects and may offer an effective and safe alternative for the treatment of itch in familial cutaneous amyloidosis.
Lichen amyloidosis is a subtype of primary localized cutaneous amyloidosis (PLCA) and is characterized by circumscribed, highly pruritic, hyperkeratotic, and hyperpigmented papules occurring typically over the shins, outer aspects of upper arms, and on the upper back . It occurs more commonly in certain populations , particularly the Chinese. Treatment is often unsatisfactory and various treatments, such as topical corticosteroids, topical calcipotriol, photochemotherapy , oral acitretin , and thalidomide  have been previously reported with variable results. As more data on the pathophysiology of PLCA becomes available , new and more targeted treatments can be used for this condition.
In this report, we describe the efficacy of amitriptyline, a tricyclic antidepressant, in pruritus of two patients with lichen amyloidosis. We assessed the following parameters before and after 6 weeks of treatment with amitriptyline: itch score on a visual analog scale (VAS), itch frequency, and the Dermatology Life Quality Index (DLQI) . The itch VAS is a numbered 10-cm line ranging from 0 (described as “no itching”) to 10 (described as “worst itch imaginable”). DLQI consists of 10 questions, which assess the degree in which itch has affected the patient's life in the past week and it ranges from a minimum total score of 0 to a maximum score of 30.
A 63-year-old Chinese male presented with a 5-year history of extensive, pruritic, and hyperkeratotic papules over his shins, which were clinically characteristic of lichen amyloidosis (FIG. 1). His mother and brother had the same condition. His other medical conditions consisted of mild atopic eczema affecting the trunk and hypertension. The patient was mainly disturbed by pruritus occurring over his shin lesions; his itch score was 8.5 of 10 and the itchy sensation occurred twice a day on average. The condition, however, did not affect his daily living and his DLQI score was 0 of 30. He had previously tried various topical agents on his shins, including class I potent steroids and salicylic acid ointment, but did not experience any improvement. Antihistamines, both sedative and nonsedative, were also not helpful.
Amitriptyline was started at 10 mg every night and he was not given any other concurrent treatment (such as topical agents or antihistamines). He was first reviewed 3 weeks later, during which he reported a marked improvement in his symptoms. His itch score was reduced to 2 of 10 and the frequency also decreased to once a day on average. He experienced mild drowsiness from the medication during the first week of treatment but this abated subsequently. When he was reviewed again 6 weeks after starting amitriptyline, he reported the itch over his shins had completely resolved. He was maintained on amitriptyline 10 mg o.n. and at 8 months after taking the medication, his itch had not recurred. The lesions of lichen amyloidosis had remained the same despite the resolution of itch.
A 50-year-old Chinese male presented with a 4-year history of lichen amyloidosis, consisting of extensive, gradually increasing, pruritic, and hyperkeratotic papules affecting his shins (FIG. 2) and extensor aspects of his forearms (FIG. 3). His mother was similarly affected. His only medical problem was hypertension. He was previously treated with multiple types of topical steroids (including class I agents) and antihistamines (sedative and nonsedative) for his condition, but there was minimal improvement. His itch score was 5 of 10, with itch occurring 3 days a week on average. His DLQI score was 14 of 30, signifying a large effect on the patient's life .
Amitriptyline was started at 10 mg every night. The patient was not on other concurrent oral or topical treatment for itch. When reviewed three weeks later, his itch score was reduced to 1.5 of 10, and the frequency of itch occurring had decreased by 30% to 40% subjectively to twice a week on average. He did not experience any side effects, such as drowsiness. When reviewed at 6 weeks after starting amitriptyline, his itch score was 1 of 10 and the frequency of itch occurring had reduced by about 70% compared to the start of treatment, to once a week on average. His DLQI at the sixth week of treatment was 6 of 30, signifying small to moderate effect on daily life. The dose of amitriptyline was further increased from 10 mg to 25 mg o.n. but there was no difference in effect after 2 months of treatment at the higher dose. The dose of amitriptyline was thereby reduced back and maintained at 10 mg o.n. Six months after initiation of amitriptyline, his itch remained controlled. Despite the marked reduction in itch, there was no difference in the clinical appearance of the lesions.
Recent molecular studies on familial PLCA have provided insight into the mechanism of pruritus in the condition . Missense mutations were identified in the oncostatin M receptor (OSMR) gene, which encodes OSMRβ, a component of both the OSM type II receptor and IL-31 receptor. Abnormalities in either of these receptors could have led to apoptosis of basal keratinocytes, resulting in the deposit of amyloid material at the dermoepidermal junction and upper dermis. These receptors were also found in the dorsal root ganglia of peripheral nerves. Maddison et al. reported a reduction in cutaneous nerve fibers in PLCA and postulated that the hypersensitivity of the remaining nerve fibers can cause intense itch . We thereby selected an agent indicated for neuropathic itch, namely, amitriptyline , to treat our patients.
Amitriptyline is a tricyclic antidepressant. For treating pruritus due to neuropathy, it is usually started at a lower initial dose of 10 to 25 mg compared to 25 mg as an antidepressant. The dosage is to be gradually titrated upwards according to therapeutic effect. Its mode of action may be related to its inhibition of the reuptake of 5-HT and noradrenaline in the brainstem and spinal cord and the inhibition of voltage-dependent sodium and potassium channels in peripheral nerves. Freysoldt et al. also reported an inhibitory action of amitriptyline on nicotinic acetylcholine receptors in unmyelinated nociceptive axons . It is possible that these actions can ameliorate itch in a similar fashion to neuropathic pain. Although amitriptyline is, in addition, a potent histamine H1 receptor blocker , we do not think this mechanism was responsible for the reduction in itch in our patients, as previous potent antihistamines had not worked for them. Of note, other tricyclic antidepressants similar amitriptyline, namely, doxepin  and trimipramine , had been used to control itch.
In our patients, in addition to a reduction in itch intensity, there was improvement in the frequency of itch occurring and their quality of life affected by the condition, supportive that the treatment was effective for their overall well-being. The observation in these cases also supports the hypothesis that small-fiber neuropathy plays a major role in the pathogenesis of itch in PLCA.
Itch in PLCA can be debilitating and treatments are generally not effective. We described the use of amitriptyline as a novel therapy in two patients. There was significant improvement in itch intensities, itch frequencies, and quality of life affected after 6 weeks of therapy. Low-dose amitriptyline poses low risk of side effects and may offer an effective and safe alternative for the treatment of itch in PLCA.