Psoriasis is a common chronic inflammatory condition of the skin, which also has nails and systemic involvement. Psoriatic involvement of the nail bed or nail matrix results in nail psoriasis. ^[1] Nail involvement is a visible indicator to predict future joint inflammatory damages and disease activity. Nail psoriasis can manifest clinically as a wide variety of nail changes, like nail discoloration, subungual hyperkeratosis, pitting and onycholysis, depending upon the part of the nail units affected. Patients with psoriatic nails have impaired quality of life due to the appearance of nails, and significant morbidity and functional impairments may arise in large cases. Its management is challenging because it is long term, and often not satisfying the patients leads to depression, which further deteriorates the condition. Patient education with explaining the prognosis and outcomes of the treatment is the most important aspect. ^[2]

The exact etiology of nail psoriasis is unclear, but multiple factors may contribute to being the etiology of nail psoriasis, which include genetic, immunological, and environmental factors. However, dysregulation of innate immunity is thought to be the stronger associated factor, while genetic factors are not well understood. Family history is common, and human leukocyte antigens (Cw6, B13, B17) are associated with it. ^[3]

Nail psoriasis affects both children and adults. It equally affects males and females and has increase prevalence with increasing age. Nail Psoriasis mostly develops in association with cutaneous psoriasis and psoriatic arthritis with a prevalence of 10% to 55% and 80% to 90%, respectively. Nail psoriasis may develop as a sole manifestation. The involvement of nail in a patient with cutaneous psoriasis is concurrent or develops after the onset of cutaneous symptoms. ^[4]

Nail psoriasis usually results from psoriatic inflammation involving the nail bed or nail matrix. The matrix of the nail is mainly responsible for nail plate formation and is located beneath the proximal nail fold. The superficial part of the nail plate is formed from the proximal nail matrix while the deep part is formed from the distal nail matrix. The nail bed lies directly beneath the nail plate and plays a significant role in the adherence of the nail plate to the nail bed. ^[5] Clinical features related to nail matrix involvement are nail Pitting, red spots in the lunula, leukonychia, and crumbling of the complete nail plate. The involvement of the nail bed manifests clinically as Onycholysis, splinter hemorrhages, subungual hyperkeratosis, and oil drop discoloration. ^[6]

Genetic contributions to the formation of nail psoriasis are still uncertain. Psoriatic nail disease may, however, align more closely with innate immunity dysregulation. Thus, psoriatic nail disease can contribute differently to innate and adaptive immunity than the disease limited to the skin. ^[7]

Histopathological findings of nail psoriasis are similar to cutaneous psoriasis, and it includes mild to moderate hyperkeratosis, spongiosis, and focal hyperkeratosis. Other prominent features are neutrophilic inflammatory infiltrate, hypergranulosis, and papillomatous epidermal hyperplasia. Papillary dermis shows dilated tortuous inflamed capillaries. The hyponychium shows the loss of the granular layer while there is hypergranulosis in the nail bed and matrix of the nail. ^[8] 

All the psoriasis patients attending the outpatient department of dermatology and venereology at a tertiary referral center in Hyderabad for a period of 1 year were included in this cross-sectional study.

Exclusion criteria

Patients receiving/have received systemic antipsoriatic medications or topical nail medications in the past 3 months and patients with concomitant onychomycosis proven by microscopy and/or culture were excluded from the study.

A detailed history was taken in each patient with particular reference to cutaneous complaints including duration, progression, and treatment modalities. Based on the age of onset of disease, patients were classified into early-onset group (age of disease onset <40 years) and late-onset group (age of disease onset at or after 40 years). A thorough clinical examination was done and extent of skin disease was documented using Psoriasis Area Severity Index (PASI) score. Based on PASI score, patients were classified into mild (PASI <10), moderate (PASI 10–20), and severe disease (PASI >20). All the fingernails and toenails were examined in a well-lit environment, under a magnifying lens to visualize the nail findings, and NAPSI score was calculated for each patient.

NAPSI scoring

In this scoring system, each quadrant of the nail is evaluated for the presence or absence of nail matrix disease (pitting, leukonychia, red spots in lunula, and nail plate crumbling) and for nail bed disease (oil drop [salmon patch] discoloration, onycholysis, nail bed hyperkeratosis, and splinter hemorrhage).

Each nail gets a matrix score and a nail bed score, the total of which is the score for that nail (0–8). The sum of the individual nail scores is the total NAPSI score of the patient. The sum of the scores for all of the finger and toenails varies from 0 to 160 and is the nail psoriasis severity score for that patient at that time.

Relevant investigations including KOH mount and fungal culture and skin biopsy were carried out wherever required, to confirm the diagnosis. The Statistical Package for the Social Sciences (SPSS v. 11.0) software was used to analyze the data collected in this study. Mean and standard deviations were compared between patients with and without nail psoriasis using t-test for independent samples. Categorical variables were summarized as number and percentages of all patients and evaluated using Pearson’s Chi-square test

A total of 90 patients with psoriatic nail involvement were included in the study. The mean age of the patients was 44.1± 11.2 years (range 14-74 years). Fifty-five percent of patients had the disease for more than 5 years, and the duration of treatment ranged from 0.2 to 11 years (4.9 ± 2.6 years). The mean body mass index (BMI) of the study population was 26.3 ± 3.2 kg/m2. Hypertension was the commonest comorbidity (Table 1).

Table 1. Socio-Demographic Details of Patients (n=120)

BMI = body mass index.

Table 2. Frequency Distribution of Clinical and Dermoscopic Nail Bed and Nail Matrix Findings Among Patients

Chronic plaque psoriasis was the commonest clinical presentation (79.2%) and 72.5% of the patients had a PASI score <10; 51.7% of study subjects had a NAPSI score bewteen 6 and10. Arthritis was noted in 11.7% of cases (n = 14), 90% (n = 108) had a CASPAR score of 3 or more. The mean numbers of fingernails and toenails affected were 3.5 ± 1.2 and 3.6 ± 1.5 with a mean NAPSI score of 10.1 ± 6.1. A larger number of nail changes were detected with dermoscopy. Nail matrix signs were noted in 95.8 % of cases and nail bed signs were noted in 85.0% of cases. Clinically, nail plate thickening (56.7%) and subungual hyperkeratosis (50.8%) were the most common presentations and, on dermoscopic examination, pitting (72.5%) and subungual hyperkeratosis (68.3%) the most frequent ones (Figure 1) (Table 2).

Table 3. Comparison of Mean Ranks of Nail Psoriasis Severity Index Among Different Durations of Onset of Disease in Months

¥-modified NAPSI; §-dermoscopic NAPSI; *statistically significant difference at P < 0.05

dNAPSI = dermoscopic NAPSI; dmNAPSI = dermoscopic modified NAPSI; NAPSI = Nail Psoriasis Severity Index.

Though none of the severity measure scores (NAPSI, dNAPSI, mNAPSI and dmNAPSI) were statistically sig- nificant (P > 0.05) for joint involvement, dmNAPSI scores showed higher odds ratio values, indicating that unitary increase in dmNAPSI scores increased the odds of being in the CASPAR scores of 2, 3 and 4 by 2.10 times, 2.19 times, and 2.13 times compared to a CASPAR score of 5. Similarly, NAPSI scores showed higher odds ratio values, indicating that unit increase in NAPSI scores increased the odds of being in the CASPAR scores of 2, 3 and 4 by 1.58 times, 1.85 times and 2.03 times compared to a CASPAR score of 5. The odds of NAPSI scores increased with increase in the grades of severity of joint involvement based on CASPAR criteria, and odds of dmNAPSI remained almost the same, with no statistical difference between these two (P > 0.05) (Table 4).

The mean ranks of mNAPSI increased significantly with the duration of the disease (1-6 months = 47.57; 12-60 months = 60.00; >60 months = 67.34, with P < 0.05), except at 6-12 months (31.88, P > 0.05). The mean ranks of other scores, ie dNAPSI, dmNAPSI and NAPSI, did not vary sig- nificantly in relation to the durations of the disease (P > 0.05) (Table 5).

Nail involvement in psoriasis is relatively less explored and often ignored, especially in the Indian setup. The present study evaluated clinical and serological profile of 38 psoriasis patients with nail involvement.

The most common clinical nail change in our series was found to be pitting followed by onycholysis and subungual hyperkeratosis. This finding is in concordance with earlier reported work.  Nail fold lesions were found in a large proportion of our patients (26/38; 68.4%) and frequency was even higher in patients with psoriatic arthritis (8/9; 88.9%). Red lunula although considered to be less common in psoriasis was observed in 7.9% (3/38) subjects.

The mean nail psoriasis severity index scores vis-a-vis cutaneous severity were higher in our study as compared to previous studies both from India and elsewhere.[9],[10],[11],[12],[13] Higher nail psoriasis severity index scores in patients with concomitant arthritis are well known and are found in our study as well. We also observed that psoriasis area severity index showed a weak positive but statistically insignificant correlation with nail psoriasis severity index (r = 0.26; P = 0.12), demonstrating worsening of nail involvement with increased severity of skin disease.

Interestingly, although nails were considerably affected (overall high nail psoriasis severity index scores), the impact on quality of life (nail psoriasis quality of life 10 scores) was relatively low (mean 1.1 ± 0.4) in our study cohort. This is in contrast to Western studies documenting a higher impact on quality of life. Klaassen et al. reported mean nail psoriasis quality of life 10 score of 9.9 ± 14 in their study. This was also found to correlate with self-administered psoriasis area severity index.[13] This apparent discrepancy could be because most of the questions included in nail psoriasis quality of life 10 may not be particularly relevant to Indian patients. Majority of our patients belonged to lower socioeconomic strata with a good family/social support system found in many Indian joint families. Thus, a question analyzing their ability to drive a car stands irrelevant for the vast majority seeking care at a government-run tertiary care center. Similarly, when asking about ability to lock–unlock door, we realized that most of our patients did not have to do these so-called “daily activities” on their own because of a good support system. We found that many of our patients were even unaware of their nail disease or not bothered because it did not interfere with their daily living. Cosmesis also was not of much concern for most of our subjects. Probably, we need a more practical questionnaire suited to evaluate impact of nail psoriasis on the quality of life in Indian subjects.

Among clinical features, patients with psoriatic arthritis were commonly found to have intergluteal, perianal and periungual lesions of psoriasis [Figure - 3]. Involvement of these sites is also regarded as a predictor for the development of psoriatic arthritis.[14],[15] A closer follow-up and awareness regarding joint involvement in these patients may help in early diagnosis and efficient management. Periungual disease was also associated with higher nail psoriasis severity index scores.

Psoriasis is a chronic inflammatory disease associated with an activation of a cascade of inflammatory mediators. Various markers of inflammation have been used to assess disease activity as well as response to treatment. The commonly used and easily available ones are c-reactive protein and erythrocyte sedimentation rate. Although both are assumed to be similar markers of inflammation, in reality they serve different purposes. Erythrocyte sedimentation rate rises slowly after an insult and also declines slowly after the stimulus is removed, remaining elevated for weeks thereafter. On the other hand, c-reactive protein has a shorter half-life (6–8 h) and is a marker of acute insult or inflammation. It also rapidly comes down with treatment. Thus, erythrocyte sedimentation rate is good for long-term monitoring, whereas c-reactive protein levels reflect day-to-day variation of disease activity.[16] C-reactive protein is a sensitive marker of inflammation although not specific.[17],[18] In a multicentric study, examining the characteristics of 1306 Italian patients with psoriatic arthritis, c-reactive protein was elevated in 52.6% of the cases.[19] 

Another study from India, documented raised c-reactive protein in 62% patients with psoriatic arthritis.[11] In our patients, c-reactive protein was raised in 15/38 (39.5%) of subjects and erythrocyte sedimentation rate was raised in 22/38 (57.9%).

Both rheumatoid factor and anti-cyclic citrullinated peptide antibodies are well-established markers of rheumatoid arthritis. The former has a sensitivity of 69% and specificity of 85% for rheumatoid arthritis.[20] Anti-cyclic citrullinated peptide antibodies are antibodies against synthetic citrullinated peptides and are considered to be more specific marker for rheumatoid arthritis (specificity being 95%–96%) but with lower sensitivity (53%–68%).[21] van Gaalen et al. reported that 93% of anti-cyclic citrullinated peptide positive patients with undifferentiated arthritis went on to develop rheumatoid arthritis over a 3-year of follow-up as compared to 25% of anti-cyclic citrullinated peptide negative patients.[22]

Classically, psoriatic arthritis is a seronegative arthritis; however, rheumatoid factor may be positive in 10% patients, making psoriatic arthritis “usually seronegative.”[23],[24],[25],[26] Different studies have shown varying results with Böckelmann et al. reporting it positive in 8/62 (12.9%) patients,[27] whereas Shibata et al. reported it in 1/15 (7%) patients.[26] Other studies have reported rheumatoid factor positivity in 5%–19% of psoriatic arthritis patients.[22],[25],[27] However, there may be quantitative differences with serum levels of rheumatoid factor being higher in the patients with rheumatoid arthritis than in those with psoriasis or psoriatic arthritis. The present study found 5/38 (13.2%) patients to be rheumatoid factor positive. It was higher in patients with psoriatic arthritis (22.2%) as compared to those without arthritis (10.3%). Thus, our findings are in congruence with previous studies.

Anti-cyclic citrullinated peptide antibodies have been reported to be varyingly elevated in patients with psoriasis.[23],[24],[25],[26],[27],[28],[29] In patients with psoriatic arthritis, studies have documented positive anti-cyclic citrullinated peptide antibodies in 5%–20% of patients with psoriatic arthritis.[23],[24],[25],[29],[30] These patients have been found to have more severe arthritis than seronegative patients. In psoriasis without arthritis, highly variable levels of anti-cyclic citrullinated peptide have been reported; varying from as low as 0/15 (0%) patients [29] to as high as 11/62 (17.7%).[27] Our cohort had 4/38 (10.5%) positivity to anti-cyclic citrullinated peptide antibody with 22.2% of psoriatic arthritis group being positive and only 6.9% of psoriasis without arthritis patients displaying positivity. In view of the highly variable results obtained in different studies, it is difficult to draw any definite conclusion as of now. We need more data from larger study populations.

Overall, patients with psoriatic arthritis demonstrated higher levels of inflammatory mediators such as erythrocyte sedimentation rate and c-reactive protein as well as serological markers such as rheumatoid factor and anti-cyclic citrullinated peptide antibodies. The inflammatory markers can be of help in following the course of the disease, whereas the serological markers may act as a hindrance to a definitive diagnosis of psoriatic arthritis as per existing diagnostic criteria. With an increase in our knowledge and awareness, one can remain open to a diagnosis of psoriatic arthritis in undifferentiated seropositive arthritis, helping long-term treatment plans and prognosis.

Limitations

Our study was carried out on a relatively small cohort of patients with skin and nail involvement with psoriasis. Larger studies involving more numbers of patients of psoriasis with or without nail disease and/or joint disease can help clarify issues. Inclusion of matched controls from general population was also not done. If included in future works, this can help us clarify about the sensitivity and specificity of inflammatory and serological markers.

Our study documents nail changes in psoriasis and severity of involvement in the Indian context. We found discordance between the extent of nail involvement (as scored by nail psoriasis severity index) and the impact on quality of life (as evaluated by nail psoriasis quality of life 10). This lack of congruent impact suggests that probably the scoring systems need appropriate adaptation suited to the Indian population. Furthermore, a high proportion of patients had raised levels of immune and serological markers. Such reports in arthropathies other than rheumatoid arthritis raise a word of caution in their interpretation for diagnostic purposes. It can be seen that a close monitoring and follow-up of psoriatic patients with nail disease is of utmost importance. Further controlled studies with a larger population-based sample size are warranted before definite conclusions can be reached.

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