Psoriasis of the nails L40.8

A frequent manifestation of psoriasis with varying degrees of severity, especially in severe cases, which places considerable psychological and physical-motor stress on a patient and occurs on one or more nails (see nail below). Patients with associated psoriatic arthritis are affected by "nail changes" at diagnosis with up to 80%. The disease is probably the most common disease of the nails after nail mycosis. Psoriatic onychopathy is often associated with a severe course of psoriasis (early onset, high risk for psoriatic arthritis)and can lead to significant functional limitations and decreased quality of life. Remarkably, the fingernails are more frequently involved than the toenails. Basically, nail psoriasis is considered difficult to treat due to the fact that the nail plate is a hydrophilic "keratin gel" with high density. This impedes the penetration of topical agents, so that they often remain ineffective. In addition, the previously practiced injections (e.g., triamcinolone injections) near the matrix or nail bed are extremely painful and not without complications. The indication for systemic treatment is a major medical challenge.

Roughly, psoriatic nail dystrophies can be explained by pathologic changes in

• of the proximal nail matrix
• of the distal nail matrix
• as a result of complex pathologies of nail matrix and nail folds

Psoriatic pathologies of the proximal nail matrix

• Spotted nails (in about 75% of psoriatic patients)
• Lacunar nail plate defects (corresponding to oversized stipples)
• Thickening, structural changes and discoloration of the nail plate (in 50% of psoriatic patients)
  • Transverse grooves
  • Longitudinal grooves
  • Rubbing pattern

Psoriatic pathologies of the distal nail matrix

• Oil stain (in 30% discolorations due to psoriatic parakeratosis of the nail bed; there is no direct connection to the free nail edge)
• Distal onycholysis (in 46% due to subungual hyperkeratosis)
• Pressure pain of the nail, not infrequently in combination with oil staining (50% of affected persons)
• Splinter hemorrhage (smallest elongated hemorrhages under the nail plate)
• Nail bed pustulosis (formation of sterile subungual pustules in the area of the proximal and/or distal nail matrix)

Complex pathologies of the nail matrix and nail fold with involvement of multiple compartments of the nail organ (combined occurrence of mottling, nail rippling, onychogryposis, psoriatic pustulosis, synechiae, and anonychiae as a scarring end state)

• Psoriatic onychogrypose (paradoxical nail growth)
• Psoriatic crumbling nail (maximum form of psoriatic onychodystrophy with disturbance of length growth)
• Psoriatic anonychia with synechiae of nail bed and nail fold, as final state of a complex psoriatic nail dystrophy

Psoriasis is the skin disease that most commonly affects the nails and is probably the most common nail disease after nail mycosis.

Nail psoriasis occurs in about 40%-50% (numbers diverge in the literature; (Salomon JC et al. 2003; Armesto S et al. 2011; Rachakonda TD et al. 2014) of all psoriasis patients, or in 70-80% of all pat. with psoriatic arthritis (see Psoriasis arthropathica below) (Canal-García E et al. 2022; Augustin M et al. 2010).

Most studies assess the prevalence of nail involvement in cutaneous psoriasis studies. There is a positive correlation between the presence of nail psoriasis, the duration of psoriasis, and between the severity of nail involvement and the severity of skin and joint changes. Here, the anatomical/physiological connections between the enthesis of the extensor tendon and the nail apparatus are a possible reason (presence of enthesitis) for the close association between nail and joint diseases. The prevalence of solitary nail involvement (psoriatic nail involvement sine psoriasis) has been described as up to 6% (Rigopoulos D et al. 2014).

Childhood nail psoriasis has a prevalence of 17-38% and is associated with a severe course of psoriasis (Al-Mutairi N et al 2007; Augustin M et al 2010; Mercy K et al 2013).

Nail psoriasis is characterized by various clinical manifestations that may occur in isolation or in combination on single or multiple fingernails or toenails.

In a larger cohort, the following were found

• spotted nails in 75% of psoriatic patients (not specific to psoriasis, also seen in chronic hand dermatitis)
• in 50% a thickening and white-yellowish discoloration of the nail plate
• in 46% (distal) onycholysis
• in 30% yellowish-brown discoloration due to parakeratotic keratinization of the nail plate (oil stain)
• 50% of the affected complained of pain (mostly pressure pain).

Furthermore:

Splinter hemorrhages (smallest elongated hemorrhages below the nail plate)

Subungual hyperkeratosis (caused by psoriatic areas in the distal nail bed and/or hyponychium;

Paradoxical nail growth: increased thickness growth of the nail at the expense of longitudinal growth.

Psoriatic paronychia: inflammatory involvement of the paronychium with varying degrees of swelling and scaling. Frequent thickening or even loss of the cuticle (eponychium).

Psoriatic crumbling nail, as the maximum form of psoriatic onychodystrophy.

Pustular nail psoriasis with formation of sterile pustules. Tends to scarring atrophy. Acrodermatitis continua suppurativa can be considered as the maximum form.

The etiopathogenesis of psoriatic nail involvement is unclear so far. Some authors discuss variations in the IL1RN gene, a regulator of the proinflammatory activity of IL-1A. The encoded cytokine has been shown to cause nail changes and therefore may be responsible for psoriatic nail pathology (Julià A et al. 2012. In psoriasis, several psoriasis susceptibility alleles are known, with HLA Cw0602 being the best studied (Dand N et al. 2020). However, nail involvement is less common in this haplotype (Ogawa K et al. 2020).

In general, the nails of the hands are affected significantly more often than the toes. The fourth finger and the first toe are preferred (Brazzelli V et al. 2012). Clinical findings also differ between fingernails and toenails. Typically, fingernails are affected by mottling, whereas nail hyperkeratosis and onycholysis are more common on toenails (Brazzelli V et al. 2012).

Nail psoriasis is characterized by various clinical manifestations that may occur in isolation or in combination on single or multiple fingernails or toenails.

In a larger cohort

• spotted nails in 75% of psoriatic patients (not specific to psoriasis, also seen in chronic hand dermatitis)
• in 50% a thickening and white-yellowish discoloration of the nail plate
• in 46% (distal) onycholysis
• in 30% yellowish-brown discoloration due to parakeratotic keratinization of the nail plate (oil stain)
• 50% of the affected complained of pain (mostly pressure pain).

Furthermore:

• Splinter hemorrhages (smallest elongated hemorrhages below the nail plate)
• Subungual hyperkeratosis (caused by psoriatic areas in the distal nail bed and/or the hyponychium).

• Transverse grooves/longitudinal grooves: Transverse grooves of the nail plate occur in the wake of chronic, and psoriatic involvement of the proximal nail matrix. Not infrequently, densely staggered psoriatic transverse grooves are accompanied by shingle-like surface exfoliation of the nail plate. Transverse grooves are not infrequently combined with dehiscence of the nail folds and nail plate. In the area of the proximal nail fold, this leads to a loss of the cuticle, which means that a protective function of the nail organ is lost.

• Longitudinal grooves: Longitudinal grooves are usually rather discrete in psoriasis. They have no diagnostic value typical for psoriasis, because they are also frequently found in ageing nails.

• Rubbed iron nail(trachyonychia): A rubbing iron-like nail surface is usually observed as a result of severe generalized psoriasis. The rubbing iron nail - trachyonychia - is the result of diffusely disturbed function of the proximal nail matrix. Trachyonychia should be classified as a nonspecific nail dystrophy, since it can also be observed in other generalized skin diseases (e.g., erythroderma/ichen planus).

  Psoriatic paronychia: inflammatory involvement of the paronychium with varying degrees of swelling and scaling. Frequent thickening or even loss of the cuticle (eponychium).

• Psoriatic onychgryposis: Onychogryphalic nails are an indication of a severe complex disorder especially of the distal and proximal nail matrix. Due to chronic psoriatic inflammation, there is a disturbance of horizontal-distal growth. This finding is not psoriasis-specific and can also be observed in other digital pathologies of the skin (e.g. in erythroderma), as well as in recurrent trauma of the nail matrix (e.g. in soccer players).

• Psoriatic crumb nail, as a maximum form of psoriatic onychodystrophy.
• Pustular nail psoriasis with formation of sterile pustules. Prone to scarring atrophy. Pustulosis of the nail bed can lead to complete anonychia. Acrodermatitis continua suppurativa may be considered the maximal form.

Comorbidities and associated factors

• Psoriatic arthritis: Psoriatic arthritis is the most common comorbidity in psoriasis, occurring (clinically) in 5-42% of patients (McGonagle D et al 2009). Approximately 80-90% of patients with psoriatic arthritis develop nail involvement (Lai TL et al 2016). Patients with psoriatic arthritis are significantly more likely to develop psoriatic onychopathy than those with only skin involvement (Lai TL et al. 2016). Thus, it is also postulated that nail involvement is a predictor of enthesopathy. The clinical association between enthesopathy and onychopathy is explained by the anatomical proximity of extensor tendon of distal phalanx and nail matrix(Tan AL et al. 2007; Tan AL et al. 2007; Wilson FC et al. 2009; Williamson L et al. 2004; Kaeley GS et al. 2021).
• Onychomycosis: The clinical differential diagnosis between nail psoriasis and onychomycosis is often difficult. Moreover, coexistence of the two diseases occurs in 30% of patients with nail psoriasis (Zisova L et al. 2012; Klaassen KMG et al. 2013). It is postulated that morphological changes in psoriatic nails are predisposing factors for onychomycosis and that onychomycosis may act as a Köbner phenomenon for the development of psoriatic onychopathy (Klaassen KMG et al. 2013). The consequence of this frequent coexistence of onychomycosis and nail psoriasis is that cultural fungal exclusion is recommended before starting treatment, especially when immunosuppressive drugs are needed (Kaul S et al. 2018). Meanwhile, some centers have a rapid diagnostic test consisting of an immunochromatographic assay that can detect Trichophyton antigens in nail samples and provide immediate results with sufficient quality (Paugam A et al. 2021).
• Smoking: Apparently, smoking is an independent risk factor for psoriasis (Armstrong AW et al.2011). Recently, it has been shown that smoking psoriatic patients are more likely to develop psoriatic onychopathy than non-smokers (Temiz SA 2020).

The classic histologic features of nail psoriasis overlap with the findings of cutaneous psoriasis and include: mild to moderate hyperkeratosis, focal parakeratosis, psoriasiform papillomatosis, dilated and tortuous capillaries in the papillary dermis, and neutrophilic infiltrates (Grover C et al 2005). In addition, there may be loss of stratum granulare in the hyponychium and hypergranulosis in the nail matrix as well as in the nail bed (Grover C et al 2005). The matrix epithelium in the area of a stippling usually shows mild spongiosis with exocytosis of lymphocytes and neutrophils.

Tinea unguium (most important differential diagnosis!): Toenails are more frequently affected, slow nail growth, rarely pits, frequent onycholysis, microscopic detection of spores and mycelia (careful sampling technique); positive culture!

Onychogrypose (common in old age): Highly domed, thickened, often discolored, claw-like, hard nail plate. Formation of large, malformed nails that have grown in the "wrong direction". The nail matrix is hard and not crumbly.

Lichen planus: Mostly thinned (!) nail plates with longitudinal surface distortions(trachyonychia) and numerous spots. Complete (atrophic) destruction of the nail plate is possible.

Eczema nails: Not clearly assigned term for nail changes in chronic hand eczema. In this respect, the clinical symptoms are of different types: often irregular nail surface with grooves, furrows, spotting, splitting, thickening of the nail plate, onycholysis and color changes. No psoriatic stigmata of the skin.

Onycholysis semilunaris: Crescent-shaped incomplete onycholysis with detachment of the nail plate from the free edge. No other psoriatic stigmata.

Leukonychia (differential diagnosis see there): Polyetiologic symptom with punctate, transverse, longitudinal, or homogeneous total whitening of the nail plate (leading symptom: nail, white), which may involve one or more nails.

Yellow-nail syndrome: Thickened, yellow discolored nails throughout the nail area, slow or no growth, scleronychia with peripheral onset onycholysis.

Twenty-nail dystrophy: Often present at birth or developing in the first few months of life. Usually affects all nails. Nail dystrophies vary, mostly thickened, not crumbly, no spots or oil stains, no integumentary psoriasis.

See also Nail diseases (overview and classification).

About half of patients with nail psoriasis report limitations in their daily functions in everyday life, depending on the extent of the changes.

Around 50% of those affected report pain.

The treatment of nail psoriasis is extremely difficult and lengthy and thus requires a lot of patience. Patients unfortunately have to learn to live with the versch. Unfortunately, patients have to learn to live with the various forms of psoriatic onychodystrophy over a longer period of time. The current therapeutic arsenal of systemic therapeutics is very broad. From this broad assortment, the individual therapeutic treatment approach has to be chosen considering the clinical constellation. It includes both "wait and see" and, in severe cases, the use of systemic therapeutics. Special therapeutic consideration is required for psoriatic minus variants with solitary psoriatic onychopathy in which the local findings have led to considerable functional and psychological problems.

External therapy promises success only in milder forms. The following general rules of conduct should be observed:

• Avoid provocation factors (aggressive manicure or pedicure, manipulation of the cuticle).
• Cut nails short, especially in patients who are confronted with manual activities at work/at home/hobby.
• Before cutting, wash and grease nails (e.g. Linola grease ointment) to reduce splintering.
• If necessary, cut brittle nails only after a lukewarm oil or tar bath (Linola Fat Oil Bath, Balneum Hermal Oil Bath).
• Have transverse grooves or thickened nails milled by experienced medical chiropodists.
• Wear light, wide shoes that do not press on affected, deformed toenails.
• Artificial fingernails as an optical embellishment are possible.
• In case of psoriatic "crumb nails" occlusive treatment with 40% urea paste (see below urea (overview) soften for 10-14 days and have it milled off by a specialist.

There are few high quality studies evaluating and comparing the different topical treatments for nail psoriasis. In general, agents with a higher fat content (creams or ointments) applied under occlusion show better results than non-occlusive therapy. For nail bed manifestations, treatment should be applied as close to the nail bed as possible after clipping the onycholytic nail and performing subungual curettage (Jiaravuthisan MM et al 2007). Several therapeutic options are available.

Corticosteroids topical: Currently, there is no consensus on a standard treatment regimen. However, in clinical practice, highly potent corticosteroids are frequently used, often under occlusion and for long periods of time. Caution should be exercised in their long-term use because of the risk of skin atrophy (Kole L et al. 2014; Canal-García E et al. 2022). Alternative: try sertaconazole nail patches (Zalain nail patches; cut to nail size and change 1 time/week).
Alternative: vitamin D derivatives (calcitriol, tacalcitol, calcipotriol): These topicals are effective as monotherapy or together with topical corticosteroids (clobetasol or betamethasone). They seem to be more useful in psoriatic changes of the nail bed than in matrix-induced ones (Canal-García E et al. 2022; Rigopoulos D et al. 2022). For milder forms, try calcipotriol solution/ointment (e.g. Daivonex, Psorcutan solution) 1 time/day, preferably applied in the evening, preferably occlusive (finger cots, gloves) for at least 4-6 months.

Alternative: calcineurin inhibitors (tacrolimus): In one study, they were effective for both matrix and nail bed manifestations (De Simone C et al 2013).

Alternative: tazarotene: local treatment with a 0.1% tazarotene (cream/gel). Several positive study results (12-24 weeks therapy) are available for this (Rigopoulos D et al. 2007). This procedure seems to be topically-occlusive effective. Its use may be limited by the frequent occurrence of erythema, scaling, irritation, and paronychia (Fischer-Levancini C et al. 2012; Canal-García E et al. 2022).

Alternatively (for psoriatic onychogryposis): Application of a 15% urea varnish (Onypso). Over a period of >6 months, apply 1 x daily to the affected nails.

Alternatively: In more severe forms, local application of 1% 5-fluorouracil or a solution containing 1% 5-fluorouracil + salicylic acid or urea is recommended ( off-label use). Apply solution once daily, followed by occlusive dressing. Possible side effects are redness, itching and painful burning sensation.Electrotherapy: Interferential current therapy is also described as successful in nail psoriasis (Fa. NEMECTRON; Fa. IONTO-COMED).

Corticosteroids, intralesional: This therapeutic method is the only one with acceptable results. A depot should be placed medially and laterally below the matrix and below the nail plate. The corticosteroid should be administered with a 28-30G needle. It is advisable to use an analgesic technique in the area to avoid pain during and after the procedure (the main adverse effect). The most commonly used regimen is the injection of approximately 0.4 ml of triamcinolone acetonide at a concentration of 10 mg/ml. (Canal-García E et al. 2022; Abell e et al. 1973). Severely painful procedure, conduction anesthesia according to Oberst is required. If necessary, multiple repetition after 2-4 months. Under this therapy, clear successes have been demonstrated in various studies. Clear successes have been demonstrated in various studies (evidence level C).

General recommendations: In recent years, the treatment of skin and nail psoriasis has progressed with the development of new drugs with long-lasting efficacy (Pasch MC 2016). The approach should be individualized according to the number of affected nails, the association of skin and joint lesions, other concomitant diseases, the degree of impairment of quality of life, etc. Systemic treatments are the treatment of choice in patients with multiple nail infestations or when nail psoriasis is accompanied by skin or joint manifestations. There are few randomized clinical trials demonstrating clear beneficial clinical effects.

• Retinoids (acitretin): Retinoids have moderate efficacy with NAPSI improvements of 40-50%. They are used in lower doses than in cutaneous psoriasis (0.2-0.3 mg/kg/day). Their mechanism of action is slow, but they are drugs that can be used for years. The most common adverse effects are the well-known ones such as cheilitis and skin desquamation (Canal-García E et al. 2022; Ricceri F et al. 2013).
• Methotrexate: Seems to be most useful in manifestations of the nail matrix. The efficacy obtained is moderate, with an improvement in NAPSI scores between 40-50%. Doses used are the same as for cutaneous psoriasis. Compared to treatments with biologics, efficacy is usually lower (Reich K et al. 2011).
• Ciclosporin A: Ciclosporin A is effective in both nail bed and nail matrix onychopathy. Ciclosporin has been shown to be effective in monotherapy but is increasingly used in combination with calcipotriol. Its use is limited to about 12 months because of the risk of renal damage (Canal-García E et al. 2022).
• Apremilast: In pivotal clinical trials, the drug showed improvements in both matrix and nail bed psoriasis, with NAPSI changes of 60% at 52 weeks (Papp K et al. 2015; Lanna C et al. 2020).

Biologics: With most biologic drugs, the response of nail pathologies is much slower than on skin lesions, and is usually evident from week 12. In this case, the fingernails usually improve earlier than the toenails (faster growth). The following drugs have been studied for their efficacy in nail psoriasis:

• Infliximab: Several studies have demonstrated the efficacy of infliximab on nail bed and nail matrix manifestations. Patients with severe psoriasis improved more rapidly and to a greater extent than patients with mild psoriasis. In addition, quality of life scales improved with infliximab treatment (Reich K et al. 2010; Canal-García E et al. 2022).
• Adalimumab: Several studies, including clinical trials and population-based cohorts, have evaluated the efficacy of adalimumab in nail psoriasis and have generally shown good results (NAPSI improvements between 55-95%). This improvement was independent of prior treatment with infliximab or etanercept (Canal-García E et al. 2022; Thaçi, D et al. 2015).
• Etanercept: Several observational studies demonstrated improvements in NAPSI between 50-90% (Luger TA et al. 2009).
• Ustekinumab: Ustekinumab has been shown to be effective for manifestations in the nail bed and nail matrix, with NAPSI improvements of 57-97%. At the same time, it improved the quality of life of treated patients (Rigopoulos D et al 2011; Patsatsi A et al 2013).
• Secukinumab: 2.5-year results show sustained NAPSI improvement of about 70% and improvement in quality of life (K. Reich et al. (2021).
• Ixekizumab: Multiple studies have shown efficacy with good response rates (improvement in NAPSI 100) of up to 55% (Van de Kerkhof P et al. 2017).
• Brodalumab: Several studies, including randomized clinical trials, have demonstrated efficacy of this drug in nail psoriasis (Elewski B et al (2020).
• Guselkumab: Guselkumab became available in 2019 for the treatment of cutaneous psoriasis. In pivotal trials, this drug showed improvements in NAPSI scores at 16 weeks compared with placebo (Foley P et al 2018).
• Risankizumab: In clinical trials, risankizumab showed statistically significant improvements in NAPSI compared with placebo at weeks 16 and 52 (Gordon KB et al. 2018).
• In summary, a network meta-analysis evaluated the results of 7 comparative clinical trials of 6 biologic drugs: Patients with concurrent moderate psoriasis and nail psoriasis were included. The primary endpoint was complete disappearance of nail lesions (NAPSI, mNAPSI, or PGA of 0) at week 24-26. The probability of complete response was highest for ixekizumab (46.5%), followed by brodalumab (37%), adalimumab (28.3%), guselkumab (27.7%), ustekinumab (20.8%), and infliximab (0.8%) (Reich K et al. 2021). In concurrent psoriatic arthritis, combination with methotrexate may need to be considered.

Psoriatic onychodystrophy is often seen as a "secondary problem" to be neglected. In this context, the clinical problem can reach a serious clinical magnitude due to stigmatization, functional limitations of daily activities, secondary infections and pain.

With regard to isolated nail psoriasis, the risk-benefit profile of internal therapy must be considered!

For objectification and follow-up of nail involvement the "Nail Psoriasis Severity Index ( NAPSI) has been developed. Alternative scores are: NPQ10 (Nail Psoriasis Quality of Life - to assess the impact of nail psoriasis on the quality of life of the individual) and NAPPA (Nail Assessment in Psoriasis and Psoriasic Arthritis). Other scales used primarily in clinical trials include the modified NAPSI (mNAPSI) (Rich P et al. 2003; Cassell SE et al. 2007; Hudgens S et al. 2021).

Clinically important is the observation, confirmed in a multivariate regression analysis, that nail infestation must be considered a negative prognostic factor (Bardazzi F et al. 2017).

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