Psoriatic arthritis and nail changes: Exploring the relationship
Introduction
Psoriatic arthritis (PsA) is a seronegative spondyloarthritis associated with disease of the axial and peripheral joints, affecting upwards of 0.2% of the general population and 16% of the population living with psoriasis [1], [2], [3], [4]. Clinical manifestations differ significantly between patients, with variations including joint, spine, and entheseal involvement, dactylitis, and new bone formation [3]. Extra-articular manifestations can also vary and may include cutaneous psoriasis, psoriatic nail changes, inflammatory bowel disease, and uveitis, with the cutaneous changes typically preceding the arthritis [5], [6]. The great diversity in the presentation and progression of PsA adds to the challenge of its diagnosis.
Although skin changes are associated with PsA, psoriasis and PsA appear to have different inheritance patterns, with PsA having a stronger hereditary link than psoriasis itself [7], [8]. Furthermore, human leukocyte antigen (HLA) typing seems to vary between the subtypes of PsA as well as between those PsA patients who progress differently along the disease course than others [9]. Multiple cytokines have been found in higher amounts than usual within the synovial tissue of PsA-affected joints, giving rise to the idea that multiple factors give rise to the joint damage associated with this disease [10], [11], [12], [13]. Receptor activator of nuclear factor kappa-B ligand (RANKL), a member of the tumor necrosis factor family, and interleukins 12 and 17 are three of the aforementioned cytokines that appear to be upregulated in PsA synovium [10], [11], [12], [13]. Along with a downregulation of RANKLs opposing cytokine receptor, osteoprotegerin, these alterations have been shown to contribute to the increased bone resorption and disease in PsA [10], [11], [12], [13].
To address the high variability of PsA, the current classification criteria, the ClASsification criteria for Psoriatic Arthritis (CASPAR) criteria (Table 1), include a combination of articular and extra-articular findings, along with personal and family history [3]. Although primarily including patients who had long-standing PsA (mean activity of 12.5 years), the original CASPAR study on this topic showed a high specificity and sensitivity (98.7% and 91.4%, respectively) [3]. A high sensitivity was later confirmed in early PsA patients [14]. However, it was noted that although the CASPAR criteria has good applicability in specialty rheumatology clinics, the ill-defined nature of inflammatory arthritis with regard to joint, spine, or entheseal disease may be problematic outside of these specialized clinics [14].
One of the CASPAR criteria, new bone formation in the juxtaarticular region on radiography, has lead researchers to look into new ways to discover such changes [3]. Recently, magnetic resonance imaging (MRI) and ultrasound imaging have become helpful tools in imaging the bone changes associated with PsA [15], [16], [17], [18], [19], [20], [21], [22], [23]. These imaging modalities may offer an explanation for why nail changes are associated with PsA. The use of new imaging techniques has led to the proposition that nail changes represent an enthesitis of the nail bed and matrix due to an association that exists between these structures and the nearby tendons and ligaments [16], [17], [18], [19], [20], [21], [22], [23], [24].
PsA nail changes are typically divided into those involving the nail matrix vs. those involving the nail bed [25]. When nail matrix disease is present, the typical findings include pitting, leukonychia, nail plate crumbling, red spots on the lunula, and onychorrhexis (Fig. 1). This is in contrast to oil spot changes, onycholysis, subungual hyperkeratosis, and splinter hemorrhages, which are signs of nail bed disease (Fig. 2) [26], [27], [28].
Each of the different nail changes arise from unique processes within the nail complex. The loss of abnormal keratinocytes situated on the nail plate as it grows past the cuticle leaves divots or pits in its place [26], [28], [29]. Leukonychia are white discolorations in the nail plate from inflammation in the middle portion of the nail matrix [29]. With a high degree of inflammation in the nail matrix, nail plate disfiguration or crumbling occurs [28]. Nail ridging (onychorrhexis) can correspond with linear inflammation within the nail matrix [26], [29]. Red spots on the lunula are thought to be a consequence of increase blood flow to the nail matrix [30]. Oil spot changes are simply from an increased concentration of dead or damaged cells, as well as proteinaceous fluid [26], [28], [31]. Inflammation occurring at the tip of the nail causes a detachment of the nail plate and the corresponding lifted appearance of the nail [29]. Subungual hyperkeratosis is caused by increased keratinization on the nail bed, producing a thickening of the nail bed itself [26], [29]. As the nail grows out, fragile blood vessels of the nail bed can be irritated, causing blood to extravasate, resulting in red or purple linear discolorations or splinter hemorrhages [28], [29].
The subtypes that are noted to be associated with PsA in the literature vary from study to study. In fact, even the overall number of patients with PsA who have nail changes appears to fluctuate greatly from study to study, ranging from those values less than 40% to those greater than 80% [26], [32], [33], [34], [35], [36], [37]. This review serves to consolidate the literature regarding nail findings in PsA patients.
Section snippets
Material and methods
A review of the literature was completed using PubMed, MEDLINE, and EMBASE in September 2013, encompassing years 1964–2012, in order to determine the current research on the significance of nail changes with PsA. To do this, we searched for the terms “psoriatic arthritis” AND “nail” in titles and abstracts. The articles were reviewed for those that discussed the relationship between nail changes and PsA, and 21 articles were found (Fig. 3). All articles were included regardless of study design
Results
Among the 21 articles that were used for this review, a large range of variation was found for the percentage of PsA patients who have nail changes: the lowest being 32% and the highest being 97% (Table 2). On average, 66% [standard deviation (SD) 17.7] of PsA patients had nail changes. The Cassell 2007 article was excluded from this calculation as we were unable to calculate such a percentage from their data (Table 3). The oldest two articles reviewed, from 1964 to 1979, had found 83% [38] and
Discussion
The theory that the entheses in proximity of the nail bed and the nail matrix are actually anatomically related has been highlighted in a number of studies [20], [22], [27], [55]. Researchers have put forth the idea that the nail changes, and even some of the skin changes associated with PsA, may actually originate from a Koebner response to the underlying joint disease [20], [22], [24], [27], [55]. A study that used MRI imaging in PsA patients demonstrated the close relationship of the nail
Conclusion
Given the variability of results that were observed in this review, our recommendations are that further large studies on nail changes in patients with PsA should be conducted using the CASPAR criteria as the method of recruitment so as to not restrict participation to those with just skin changes. Evaluating the subtypes of psoriatic nail changes could also be helpful to further show if any one subtype, or even a category of subtypes (nail matrix vs. nail bed changes), is more or less
Acknowledgment
We thank Dr. Lyn Guenther for her kind assistance in the analysis of nail photographs.
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