PRURITUS AS A MANIFESTATION OF SMALL FIBRE NEUROPATHY

Brenaut, E., Marcorelles, P., Genestet, S., Menard, D., & Misery, L. (2015). Pruritus: An underrecognized symptom of small-fiber neuropathies. Journal of the American Academy of Dermatology, 72(2), 328-232.

Small fiber neuropathy (SFN) is a condition caused by damage to small myelinated A[delta] and unmyelinated C fibers. The fibers are mainly involved in thermal perception, nociception, and autonomic functions of stocking and glove distribution. It affects patients with metabolic disorders, autoimmune disease, Fabry's disease, and nutritional deficiencies. SFN is a severely debilitating condition as most of the patients experience pain, allodynia, and thermal dysesthesia, and most of the treatment directed to target such symptoms has been futile. Little has been published on pruritus as major manifestation of SFN.

This study aims to determine the frequency and severity of different sensory manifestations of SFN with main focus on pruritus and its characteristics. A questionnaire was given to patients with biopsy specimens positive for diminution of intraepidermal nerve fiber density and fulfilled the inclusion criteria, which included age of 18 years and above; clinical signs of small fiber impairment (pinprick and thermal sensory loss and/or allodynia and or hyperalgesia); the distribution that is consistent with peripheral neuropathy, abnormal warmth, and cooling threshold in the foot, as assessed by quantitative sensory testing; and reduced intraepidermal nerve fiber density in the distal leg. Eligible patients were ruled out if they had any signs of large fiber impairment, any sign of motor fiber impairment, and any abnormality in sural nerve conduction. Also excluded were patients with other possible explanations for the pruritus and those who could not complete the questionnaires.

Fifty-seven patients were sent questionnaires, and 41 responded. Most patients (89.7%) reported to have been experiencing sensory symptoms for over a year. The most common symptoms reported with decreasing frequency were burning, pain, pruritus, numbness, crawling, stinging, sharp firing pains, and cold sensation. Of the 41 patients with SFN, 28 had pruritus that appeared daily or almost daily. Furthermore, similar to other dermatoses, the pruritus was more prominent at night.

Although a high proportion of patients with SFN have no identifiable cause, those that were identified were secondary to Gougerot-Sjogren's disease, diabetes, hypothyroidism, and Vitamin B12 deficiency.

REMARKS: The results show that pruritus is a common manifestation of SFN and patients with this condition may present in a dermatology clinic. It is an important consideration in differential diagnosis of pruritus as these patients will require a different approach on work-up and management. Because a significant proportion of cases were associated with Gougerot-Sjogren's disease, a careful clinical screening of patients for this condition is important. Likewise, baseline glucose for patients with SFN is suggested. Treating the underlying cause may help ameliorate sensory symptoms. Many cases will remain idiopathic. Furthermore, it has to be kept in mind that SFN of differing cause responds differently to the same medication.

SYSTEMIC THERAPY FOR PSORIASIS AND THE RISK OF HERPES ZOSTER

Shalom, G., Zisman, D., Bitterman, H., Harman-Boehm, I., Greenberg-Dotan, S., [horizontal ellipsis] Cohen, A. D. (2015). Systemic therapy for psoriasis and the risk of herpes zoster: A 500,000 person-year study. JAMA Dermatology, 151(5), 533-538.

Chickenpox, also known as varicella, is a primary infection with varicella zoster virus, most commonly seen in children. Once exposed, it can lie dormant for several years in nerve cells, reemerging as herpes zoster (HZ) or shingles. HZ is a painful blistering condition with potentially disabling long-term sequelae. Of particular concern are those with compromised immune systems. Several observational studies have shown a link between rheumatoid arthritis, inflammatory bowel disease, or both and an increased risk of HZ when taking biological medications, specifically tumor necrosis factor.

This study sets out to see if patients with psoriasis who are on systemic treatment have an increased risk of developing HZ. Patients in this cohort study were part of a very large public health database in Israel. In total, 95,941 patients with a diagnosis of psoriasis from January 2002 to June 2013 were included. Information about treatment type was collected from prescriptions and divided into three groups: systemic medications (acitretin, methotrexate, cyclosporine), biological medications (tumor necrosis factor inhibitors, ustekinumab, alefacept, efalizumab), and phototherapy (psoralen with UV-A, UV-B). Receiving treatment was defined as 3 sequential months for systemic or biological medications and 2 sequential months for light therapy. One was considered "on treatment" the day he or she started the medication or phototherapy until 30 days after cessation of that treatment or 90 days for ustekinumab. A patient not receiving one of the listed treatments for 6 months or more was considered "treatment free." To be included in the HZ-positive group, a patient had to be diagnosed and receive an anti-varicella zoster virus prescription while at the same time receiving treatment for psoriasis. The association between each type of treatment for psoriasis and the risk of HZ was examined using a type of Poisson regression model, which adjusted for age, gender, severity of psoriasis, Charlson comorbidity index, steroid treatment, and socioeconomic status. Results showed that treatment with either phototherapy (rate ratio = 1.09, 95% confidence interval [0.62, 1.93], p = .99), methotrexate (rate ratio = 0.98, 95% confidence interval [0.78, 1.23], p = .83), cyclosporine (rate ratio = 1.16, 95% confidence interval [0.48, 2.80], p = .49), or a biological medication (rate ratio = 2.67, 95% confidence interval [0.69, 10.3], p = .14) does not increase the incidence of HZ. Combination medication, however, with methotrexate and a biological medication does increase incidence of HZ (rate ratio = 1.66, 95% confidence interval [1.08, 2.57], p = .02). The use of acitretin in patients with psoriasis decreased the incidence of HZ (rate ratio = 0.69, 95% confidence interval [0.49, 0.97], p = .004).

REMARKS: The results of this study suggest that patients receiving both methotrexate and a biological medication are at risk of developing HZ, particularly those patients who already have risk factors like old age and female gender. It is possible that the combination of both methotrexate and a biological medication are additive causing increased immunosuppression or perhaps there is a drug-drug interaction causing higher blood levels of the biological medication. Using acitretin to treat psoriasis was protective against HZ likely because of its minimal immunosuppressive effects. Although this was a very large study, some medication groups (alefacept, efalizumab, and ustekinumab) had small patient numbers. Furthermore, the study indirectly looked at a patient's severity of psoriasis instead of using a standard method like the Psoriasis Area and Severity Index, which could affect some of the study's findings. Finally, patients with psoriasis receiving combination treatment are at an increased risk for HZ and should be counseled appropriately. It is suggested that these patients be considered for preventative therapy (a live attenuated HZ vaccine) before the start of combination therapy with methotrexate and a biological medication.

ASSOCIATION OF VITILIGO AND ALOPECIA AREATA WITH ATOPIC DERMATITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Mohan, G. C., & Silverberg, J. I. (2014). Association of vitiligo and alopecia areata with atopic dermatitis: A systematic review and meta-analysis. JAMA Dermatology, 151(5), 522-528.

Atopic dermatitis (AD), also known as eczema, is a chronic inflammatory skin condition often seen in children but can affect people of all ages. Its occurrence is related to both genetic and environmental factors. The skin is an important barrier against many different pathogens and irritants. People with AD have lost their skin's protective properties, leaving them vulnerable to the outside world. This disease can have a significant impact on one's self-esteem and mental well-being. Furthermore, it is often seen in combination with asthma, hay fever, and food allergies. This study evaluates if those with AD have a co-occurrence of either vitiligo or alopecia areata (AA), two other types of inflammatory skin disorders. Vitiligo is an inflammatory skin condition that occurs when melanocytes lose their pigment, causing the skin to lose its original color (depigmentation). AA occurs when the immune system (lymphocyte) attacks the hair follicles causing one's hair to fall out. To date, there is conflicting evidence to support if AD is associated with other inflammatory skin conditions. Knowing this information can help guide treatment and prognosis.

This study was a systematic review and meta-analysis of the current literature looking only at observational studies from 1946 to 2013. All patients in these studies were diagnosed with AD, vitiligo, and/or AA from either patient self-reporting or physician diagnosis. In total, 33 articles meeting study criteria were examined: 16 studies of vitiligo and 17 studies of AA. When examining the relationship between vitiligo and AD, 823 patients with vitiligo (11.7%) and 192 control patients (6.0%) had a past or current history of AD. Both patients with vitiligo and control patients who self-reported as opposed to physician diagnosed had a higher rate of AD. A pooled analysis of two studies revealed that patients with vitiligo had higher odds of AD when compared with similar controls (odds ratio = 7.82, 95% confidence interval [3.06, 20.00], p < .001). Furthermore, the data from three studies were pooled, revealing that early-onset vitiligo (<12 years) had a higher rate of AD when compared with late-onset vitiligo (>12 years; odds ratio = 3.54, 95% confidence interval [2.24, 5.63], p < .001).

Investigating the occurrence of AD in patients with AA, 1096 patients with AA (9.4%) and 14,701 non-AA patients (controls, 1.9%) had a past or current history of AD. In both patients with AA and non-AA patients, those self-reporting as opposed to physician diagnosed had a higher rate of AD. Overall, patients with AA had a higher rate of AD when compared with controls (odds ratio = 2.57, 95% confidence interval [2.25, 2.94], p < .001). Authors also wanted to see if the type of AA affected one's chance of also experiencing AD. Four studies were analyzed, and results concluded that alopecia totalis or alopecia universalis had higher odds of AD than patchy alopecia (AA; odds ratio = 1.22, 95% confidence interval [1.01, 1.48], p = .04).

REMARKS: The results of this study show that patients with AA or vitiligo have an increased risk of AD when compared with similar controls. This is particularly the case in patients with early-onset vitiligo and patients with more severe forms of AA: alopecia totalis or alopecia universalis. Results are limited by the quality of the studies used in the meta-analysis. Confounding factors like gender, severity of AA or vitiligo, disease duration, age of patients, or age of disease onset were not accounted for. Not all studies had control groups for comparison, and many had differing AD prevalence rates from what had been reported in their geographical areas. This leads to higher chances of selection bias and the study not being generalizable. Higher quality studies with greater sample sizes and less confounding factors are needed to further understand the relationship between vitiligo, AA, and AD.