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Itch may require different treatment approaches


Understanding the pattern of pruritus in various autoimmune connective tissue diseases may help physicians identify different etiologies that will inform different treatment targets to alleviate the symptom, according to researchers who examined pruritus relative to disease.

Itch is often under-evaluated and undertreated in autoimmune connective tissue diseases (ACTDs), and variations suggest that itch may require a different treatment approach in each, shows a study published in the Journal of Drugs in Dermatology,
ACTDs are a broad range of diseases primarily managed by rheumatologists. They feature immune dysregulation and often have multisystem involvement including prominent skin manifestations – the most frequent of which is pruritis and it can significantly impact on patients’ quality of life.

The most common autoimmune connective tissue diseases are systemic lupus erythematosus (SLE), dermatomyositis (DM), systemic sclerosis (SSc), Sjogren syndrome (SJO), and mixed connective tissue disease (MCTD).

However, little is known about the differences in the frequency, severity, location and timing of pruritus between the various ACTDs, so a team of researchers at the department of dermatology, Massachusetts General Hospital, Boston, set out to investigate.

“Understanding the pattern of pruritus in each disease may help us identify different aetiologies and therefore give different treatment targets to alleviate the symptom,” explains Yahya Argobi, M.D., who is also linked to King Khalid University, Abha, Saudi Arabia.

The researchers reviewed charts of 197 patients seen at the Rheumatology-Dermatology (Rheum-Derm) clinic at Massachusetts General Hospital, Boston, MA between November 2012 and December 2017 who had a confirmed diagnosis of one of a specific ACTDs, DM, SLE, SJO, SSc or MCTD.

Itch was a troubling symptom in 83% of patients with dermatomyositis (DM), 61% of those with systemic lupus erythematosus (SLE), 59% of those with Sjogren syndrome (SJO), 22% of those with systemic sclerosis (SSc), and 60% of those with mixed connective tissue disease.

In DM and SLE, itch paralleled the course of inflammatory skin manifestations in 83% and 45% of patients, respectively, and itch was more intense and more treatment resistant in 12% of patients with DM and 1% with SLE. In contrast, itch in SSc and SJO tended to occur later in the disease course in 86% and 42% of patients, respectively.

“All our itchy DM patients suffered itching on the arms and hands,” Dr. Argobi notes. While scalp itch is often cited as highly prevalent in DM, the data showed that hands, trunk and face were more common sites, he added. “However, scalp was more persistent and recurrent, may be due to less sun protection and or difficulty in applying topical treatment.”

More itching was reported by DM patients from Spring through to Fall, suggesting that DM may be more photosensitive that SLE patients.

The data also suggested that pruritus may be simultaneous with cutaneous disease of DM, with itch preceding by varying time periods eruptions of skin inflammation. “This may be a useful clinical prodrome for patients and clinicians to monitor for in case of flare,” he suggested.

Itch was more frequent and of greater intensity in DM compared with in SLE, and in SLE pruritus was more closely linked to cutaneous activity. “In SLE, pruritus did not precede clinical findings by history, and our patients did not complain of itch when we did not find inflammation on exam,” Dr. Argobi says.

Almost all of the itchy DM patients and 38% of the itchy SLE patients had been diagnosed within the last two years. In contrast SSc patients with itching had an average disease duration of more than 8 years. “This suggests that itching may be an eary warning sign in DM and a later manifestation in SSc, possibly due to skin structural changes (reduction in adnexal structures, sebum production, microbial colonization profiles or neuropeptides),” Dr. Argobi says.

The itching in SSc patients was mainly focused on the trunk and upper back and not on the most obvious sclerotic areas. “This may suggest another mechanism for itching in SSc beside skin sclerosis. Little is known about the pathogenesis of itch in SSc and a sensory peripheral neuropathic mechanism might be implicated,” Dr. Argobi says.

“Neuromodulator medications such as gabapentin and pregabalin, which have been used in treating neuropathic itch, might be very helpful in alleviating itch in SSc.”

MCTD is an autoimmune disease characterized by overlapping features of two or more connective tissue diseases and the presence of anti-ribonucleoprotein antibodies. The cutaneous manifestations usually include sclerodermatous changes and lupus-like manifestations and can present with pruritus. “The pattern of the disease reflects the location of the itch: hands in sclerodermatous pattern MCTD, and sun-exposed areas in SLE-like MCTD,” Dr. Argobi says.

Treatment “should be focused on the mechanism of the itch of their predominant background ACTD, but they may need combination therapy to address the different aetiologies of the itch they experience.”

Of the 197 patients with ACTDs seen at the Rheumatology-Dermatology clinic, 57% complained of pruritus during their initial clinic visit. Referring rheumatologists had documented pruritus in only 1% of the patients, whereas dermatologists had documented it in 94%. This “highlights the important role dermatologists can serve in the quality of life and care of these patients,” Dr. Argobi emphasizes.

At the clinic, itch was managed in most patients (81%) with medium to high potency topical steroids and antihistamines, and by adding or increasing immunosuppressive medications (methotrexate, mycophenolate mofetil, hydroxychloroquine) in the remaining patients (19%).

“The colocation of cutaneous inflammation and itch in DM and SLE support an inflammatory cause, and the use of immunosuppressives as therapy. It also suggests that increased itch may be a useful early cutaneous marker of a disease flare,” Dr. Argobi concludes.

“The later onset of itch in SSc and SJO, and the lack of response to immunosuppressives, suggests that the itch in that disease state is more related to damage than inflammation and alternate mechanisms of therapy, such as neuromodulators may be necessary.”

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