Nail psoriasis

 

Salient features

·       Approximately 50% of all psoriatic patients have nail changes at a given time, but 90% will have nail alterations at least once in their lifetime. ·       Nail involvement is even more frequent in psoriatic arthritis.  ·       Isolated nail psoriasis is not rare. ·       Nail matrix and nail bed are most commonly affected. ·       Most often precipitated or worsened by trauma. ·       The most frequent of nail changes are pits, subungual hyperkeratosis, onycholysis, salmon spots, red lunulae, splinter hemorrhages, leukonychia, and psoriatic paronychia. ·       Fingernails and/or toenails may be affected. Several nails are involved in most cases. ·       Infection with pathogenic fungi is frequent and should be treated first. ·       Treatment is often unsatisfactory.

 

Abstract

 

Psoriasis is the skin disease that most frequently affects the nails. Depending on the very nail structure involved, different clinical nail alterations can be observed. Involvement of the apical matrix results in psoriatic pits, mid-matrix involvement may cause leukonychia, whole matrix affection may lead to red lunulae or severe nail dystrophy, nail bed involvement may cause salmon spots, subungual hyperkeratosis, and splinter hemorrhages, and psoriasis of the distal nail bed and hyponychium causes onycholysis whereas that of the proximal nail fold causes psoriatic paronychia. The more extensive the involvement, the more severe is the nail destruction. Nail psoriasis has a severe impact on quality of life and may interfere with professional and other activities. Management includes patient counseling, avoidance of stress and strain to the nail apparatus, and different types of treatment. Topical therapy may be tried but is rarely sufficiently efficient. Perilesional injections with corticosteroids and methotrexate are often beneficial but may be painful and cannot be applied to many nails. All systemic treatments clearing widespread skin lesions usually also clear the nail lesions. Recently, biologicals were introduced into nail psoriasis treatment and found to be very effective. However, their use is restricted to severe cases due to high cost and potential systemic adverse effects.

 

 

Epidemiology of Nail Psoriasis

 

Psoriasis is a chronic inflammatory disease with a strong genetic background but highly influenced by environmental factors. Its prevalence is ~1–2% of the world population with considerable differences among regions and individuals with different skin types. It is the skin disease that most frequently affects the nail. Roughly one half of the psoriatics suffer from nail changes at a given time, but up to 90% will have nail alterations at least once in their lifetime. The prevalence of nail psoriasis is even higher in psoriatic arthritis. Nail lesions often appear around 10 years later than skin lesions, which may in part be the reason for nail psoriasis being observed less frequently in children. In general, cutaneous psoriasis is more severe in individuals with nail involvement.

 

 

Psoriasis tends to run in families. Among siblings, 8% are affected if neither parent has psoriasis. This percentage increases to 16-25% if 1 parent or sibling has the disease, and it reaches up to 75% if both parents are affected.

 

Psoriatic nail disease is not associated with mortality. In severe cases, patients may have functional and psychosocial impairments.

 

Males and females are affected equally by nail psoriasis, and the prevalence of nail psoriasis increases with the age.

 

Etiology and pathogenesis

 

The pathogenesis of the psoriatic nail disorder is not completely known. Nail psoriasis may be due to a combination of genetic, environmental, and immune factors. A well-known fact is that a familial aggregation of psoriasis exists. Studies have linked psoriasis with certain human leukocyte antigen subtypes (eg, Cw6, B13, Bw57, Cw2, Cw11, and B27). A T-cell–mediated inflammatory process is being investigated as part of the pathogenesis of psoriasis.

 

Neither gender nor race predilection appears to exist. There is no association of HLA-C0602 with nail and joint involvement, but nail psoriasis is often associated with an inflammation at the insertion points of tendons and ligaments giving rise to enthesitis. Thus, the nail lesions are believed to represent an abnormal response to tissue stressing of the integrated nail-joint apparatus, rather than being due to autoimmunity. The nail and joint disease may be linked to tissue-specific factors, including tissue biomechanical stressing and microtrauma that lead to activation of aberrant innate immune responses. 

 

Clinical characteristics

 

The clinical findings associated with psoriatic nail disease correlate with the anatomical location of the nail unit that is affected by the disease. The nail unit is composed of the nail plate, the nail bed, the hyponychium, the nail matrix, the nail folds, the cuticle, the anchoring portion of the nail bed, and the distal phalangeal bones. The nail plate is the largest component of the nail unit. The nail matrix gives rise to the nail plate.

 

Any defect to the matrix results in onychodystrophy of the growing nail plate. The proximal nail matrix forms the dorsal portion of the nail plate, whereas the distal matrix forms the ventral part of the nail plate. The clinical presentation may vary depending on the location and the severity of inflammation of the affected nail unit. 

Anatomy of the nail, superior view

 

 

Anatomy of the nail, sagittal view

 

 

Psoriasis causes a variety of both specific as well as ambiguous nail lesions. Fingernails are more frequently affected than toe nails, probably because they grow faster. Nail psoriasis is often divided into matrix and nail bed involvement or both. Psoriasis limited to the nails can be easily diagnosed when it produces typical signs, usually detectable only in the fingernails: psoriatic pitting, onycholysis with erythematous border and salmon patches of the nail bed.

 

1.   Oil drop or salmon patch of the nail bed

This lesion is a translucent, yellow-red discoloration in the nail bed resembling a drop of oil beneath the nail plate. This patch is the most diagnostic sign of nail psoriasis. 

2.   Pitting of the proximal nail matrix

Pitting is a result of the loss of parakeratotic cells from the surface of the nail plate.

3.   Beau lines of the proximal nail matrix

These lines are transverse lines in the nails due to intermittent inflammation causing growth arrest lines.

4.   Leukonychia of the mid matrix

Leukonychia consists of areas of white nail plate due to foci of parakeratosis within the body of the nail plate.

5.   Subungual hyperkeratosis of the hyponychium

Subungual hyperkeratosis affects the nail bed and the hyponychium. Excessive proliferation of the nail bed can lead to onycholysis.

 

6.   Onycholysis of the nail bed and nail hyponychium

Onycholysis is a white area of the nail plate due to a functional separation of the nail plate from its underlying attachment to the nail bed. It usually starts distally and progresses proximally, causing a traumatic uplifting of the distal nail plate. Secondary microbial colonization may occur.

 

7.   Nail plate crumbling

Nail plate weakening due to disease of the underlying structures causes this condition.

 

8.   Splinter hemorrhage/dilated tortuous capillaries in the dermal papillae

Splinter hemorrhages are longitudinal black lines due to minute foci of capillary hemorrhage between the nail bed and the nail plate. This is analogous to the Auspitz sign of cutaneous psoriasis, which is the pinpoint bleeding seen beneath the psoriatic plaques.

 

9.   Spotted lunula/distal matrix

This is an erythematous patch of the lunula.

 

 

Pits are the most characteristic and most frequent signs and are seen as small, sharply delimited depressions in the nail surface. They are of remarkably even size and depth. Their distribution may be haphazard or they may sometimes be arranged in parallel transverse or short longitudinal lines. Pits are uncommon on toenails. They are the result of tiny psoriatic foci in the apical matrix producing parakeratosis, which breaks off when it grows out from under the proximal nail fold then leaving these depressions. Sometimes, the parakeratosis remains and is seen as an ivory-colored spot in the proximal half of the nail plate. Pits may be single, which is not yet psoriasis specific, or multiple. Ten pits in one nail or >50 pits on all nails are regarded as proof of psoriasis. Rarely, red spots are seen in the lunula usually representing a very active psoriasis lesion with dilatation of the capillaries and thinning of the suprapapillary plate.

Total matrix affection results in complete nail destruction with crumbling of the plate, whereas leukonychia is seen when the mid- to distal matrix is affected and parakeratotic cells are incorporated into the nail plate, making it optically appear white. In most cases, psoriatic leukonychia is an ill-defined white transverse band. Splinter hemorrhages are very narrow, some millimeters long reddish-dark brown to black streaks of barely 1 mm in diameter. They are analogous to Auspitz’s phenomenon of the skin and either due to hemorrhage from the dilated capillaries in the nail bed or due to blood clots in these longitudinally arranged small vessels. Salmon or oil spots are very frequent and represent psoriatic plaques in the most distal matrix and the nail bed. This area looks like paper on which a drop of oil has fallen: a yellowish-brownish spot with a red margin shines through the plate in the center of the nail or bordering an onycholytic area. The reason for this is that the squames of the psoriasis lesions are imbibed with serum and compressed under the nail. When such a salmon spot reaches the hyponychium, the part of the parakeratosis breaks out and psoriatic onycholysis develops. Onycholysis is actually the most common manifestation of nail psoriasis and may affect both fingernails and toenails. In fingernails the presence of an erythematous border along the proximal margin of the onycholytic area is diagnostic for nail psoriasis differentiating it from most other causes of onycholysis, such as onychomycosis. In addition there is often subungual hyperparakeratosis without oil drop phenomenon causing onycholysis. In toenails, onycholysis is usually combined with subungual hyperkeratosis and may closely resemble onychomycosis. Psoriatic hyperkeratosis may be very marked and at times so extreme as to resemble pachyonychia congenita. Psoriasis affecting the dorsal as well as the ventral surface of the proximal nail fold results in swelling and rounding of its free edge. This leads to a spontaneous loss of the cuticle, thus giving the pattern of chronic paronychia. Onycholytic toenails may become secondarily colonized with Candida, environmental fungi (e.g., Aspergillus) or Pseudomonas that predisposes to distal/lateral onychomycosis in toenail. Up to 20% of psoriatic nails have secondary onychomycosis.

In psoriatic arthritis, nail involvement is often severe with psoriatic paronychia, complete nail destruction, and swelling of the distal interphalangeal joint. This has a serious negative influence on the quality of life.

In contrast, psoriatic pachydermoperiostosis is closely related to psoriatic arthritis but usually without obvious nail changes. Mainly the big toe is considerably swollen and often painful.

Pustular psoriasis occurs in three different forms, all of which also involve the nail. In the palmar plantar pustular psoriasis of Barber–Königsbeck, all the nail changes described as well as larger surface defects called elkonyxis, subungual yellow spots representing large Munro’s abscesses may be seen. Generalized pustular psoriasis of von Zumbusch occasionally causes red areas with a rim of small pustules that may affect the nail. Subungual abscesses are frequent. Acrodermatitis continua suppurativa of Hallopeau is the most notorious form of pustular psoriasis of the nails. It often begins with one single digit where the skin of the distal phalanx turns red and develops some pustules that migrate under the nail and cause nail dystrophy, which, with time, may lead to complete disappearance of the nail unit so that only a red smooth digit tip is left until the disease slowly wanes off. However, acrodermatitis continua suppurativa may also initially involve several fingers and toes and run a rapid and severe course. A mutation in the gene for the interleukin 36 receptor antagonist leading to a defect in interleukin 36 antagonist was identified in generalized pustular psoriasis and acrodermatitis continua suppurativa supporting the view that these conditions belongs to the group of auto inflammatory diseases. 

Reiter’s disease is also known as reactive arthritis. It is a systemic condition with characteristic joint, mucosal, eye, genitourinary, skin, and nail changes. The latter are very similar to pustular psoriasis. However, they often have a more brownish tint due to a higher content of erythrocytes in the pustules. Histopathology also shows spongiform pustules.

 

Diagnosis

 

In most cases, nail psoriasis is diagnosed on clinical grounds. Skin lesions elsewhere plus one or several psoriatic nail features suggest the correct diagnosis. With a good biopsy, histopathology is usually pathognomonic and helps to delineate nail psoriasis from other conditions, particularly onychomycosis. The clinical diagnosis of pustular psoriasis is made on the basis of red skin areas with a rim of small pustules. Reiter’s disease requires additional laboratory examinations.

 

 

Histologic Findings

 

A nail biopsy is needed to confirm the diagnosis of nail psoriasis in some cases and is usually taken from the nail bed.

 

Psoriasis can affect any part of the nail unit. Most changes occur in the nail plate. Histologic findings of nail psoriasis include mild-to-moderate hyperkeratosis, hypergranulosis, serum globules and hemorrhage in the corneum layer, papillomatous epidermal hyperplasia, and spongiosis.

 

Pathology of nail clipping can be helpful for diagnosis and to rule out onychomycosis. When typical symptoms are not present, diagnosis of nail psoriasis may rely on videodermoscopy of the hyponychium (magnification 40×), which shows dilated, tortuous, elongated, and irregularly distributed capillaries, a finding typical of nail psoriasis. The capillary density positively correlates with disease severity and decreases with the response to treatment

 

 

Differential diagnosis

 

Onychomycosis is said to be the most frequent nail disease. It has many features in common with nail psoriasis, both clinically and histopathologically.

 

Differential diagnosis of nail psoriasis and onychomycosis

	Psoriasis	Onychomycosis
Frequency	High, commonest dermatosis with nail involvement	Very high: up to 30–40% of all nail disorders
Course	Chronic, often recurrent	Chronic, often progressive
Symptoms	Usually cosmetically and functionally embarrassing	Embarrassing, sometimes pain
Signs	Variable, depending on nail structure involved	Variable, depending on severity and type of onychomycosis as well as pathogenic agent
Pits	Very common, regular in size and shape	Rare, irregular
Onycholysis	Common	Common
Discoloration	None to yellow	Yellow to brown
Spores and hyphae	Rarely spores	Very frequent
Transverse furrows	Rare	Rare
Skin lesions elsewhere	Very common	Often tinea pedum/manuum
Trauma	May be induced by Köbner phenomenon	Important predisposing factor
Heredity	Strong hereditary component, particularly in juvenile onset psoriasis	Autosomal dominant susceptibility to develop onychomycosis

 

Grading and assessment of nail psoriasis

 

Reliable repeatable specific validated severity and outcome measures are necessary to evaluate a disease and its response to a specific treatment. So, the nail psoriasis severity index (NAPSI), was established. NAPSI is calculated by dividing each nail into four quadrants. Each quadrant is evaluated for the presence of psoriasis manifestations of the nail matrix, such as pitting, leukonychia, red spots in the lunula, and nail plate crumbling, as well as of the nail bed, such as oil-drop phenomenon, onycholysis, subungual hyperkeratosis, and splinter hemorrhages. If any of these signs is present in all four quadrants, a score of 4 is given. A score of 0 represents no signs in any quadrant. Each nail is evaluated for a matrix and a nail bed score of 0–4. They are combined to yield a maximal score of 0–8 for each nail. All nails may be evaluated, with the total NAPSI score being the sum of the scores, up to 80 if only fingers are considered, or up to 160 if fingers plus toes are included. 

 

Associations

 

Psoriasis is a frequent skin disease. Hence, co-occurrence with other skin disorders involving the nail is rather common. The most important association is that with onychomycosis as both conditions may look very similar, but a psoriatic nail may be colonized with pathogenic fungi, and a true infection of the psoriatic nail is not infrequent

 

Course

 

Nail psoriasis is chronic but often improves and worsens without known reasons. Trauma may play an important role in the exacerbation of nail psoriasis. There may be periods without any nail alterations.

 

Management of nail psoriasis

 

Treatment algorithm for nail psoriasis

Hitherto untreated mild NP (three nails, NAPSI <16)	Topical steroid class III–IV Steroid plus calcipotriol
No improvement	Injections (steroids, methotrexate)
No improvement	Systemic antipsoriatics (MTX, CyA)	More than three nails, NAPSI >16. Unsuccessfully pretreated		Systemic antipsoriatics (MTX, CyA)
No improvement	Biologicals: TNF-α inhibitor	No improvement		Biologicals: TNF-α inhibitor
If TNF-α inhibitors no longer active or show a paradox worsening			IL-12/23 or IL-17 inhibitor
If IL-12/23 or IL-17 inhibitors no longer active			Selective p19 inhibitor (IL-23)

 

 

Management of the disease includes patient education, avoidance of trauma to the nails, and different therapeutic approaches with physical and pharmaceutical procedures and agents.

Patient counseling includes education on the nature of psoriasis, how life may be influenced by nail involvement, about the specific problems of treatment that nail psoriasis is not due to an allergy or an “unhealthy” diet and thus is not treatable with particular foods. However, smoking increases the risk of psoriasis and obesity and alcohol use are associated with a higher risk for psoriasis. It is important to avoid trauma to the nail unit that will inevitably exacerbate the condition or induce recurrences. Manicure and nail cleaning have to be performed cautiously without further traumatizing the hyponychium and attachment of the nail to the nail bed. It is helpful to explain that genes are the most important etiological factors and that the skin and nail lesions are amenable to treatment but that the genes cannot be corrected. Many genes contribute to the psoriatic personality, which may explain the enormous variability of the clinical features including the response to treatment. Particularly, chronic repeated trauma is thought to be an aggravating factor. The development of pits may be the result of micro traumata to the enthesis of the extensor tendon and the dorsal aponeurosis of the distal interphalangeal joint. They may be masked using nail varnish.

All nail psoriasis treatments require a long time, as the nail is a slow-growing cutaneous appendage. The effect of any treatment can usually not be evaluated before 3–6 months, and it may take a year or longer to reach the maximum improvement achievable with a given therapy. Pretreatment photographs are highly recommended and should be repeated at all follow-up visits to show the therapeutic result to the patients. Concomitant onychomycosis may prevent clinical cure, and it is a must to exclude fungal infection when starting nail psoriasis therapy; a single remaining altered nail during an otherwise efficacious therapy may be a hint at a concomitant mycotic infection.

Many different therapeutic measures are available. Their choice depends on various factors such as severity of nail involvement and its impact on quality of life, associated skin lesions, psoriatic arthritis, comorbidities, profession, age, patient preferences, potential risks, and not the least costs and their reimbursement.

Nail psoriasis is very recalcitrant to almost all topical treatments, whereas systemic therapies clearing the skin are usually effective also in nail psoriasis. The problem of all topical drugs is their limited penetration to the diseased tissue: through all layers of the proximal nail fold plus the underlying nail in matrix lesions, through the nail plate in nail bed psoriasis. Hence, pits, though often being rather inconspicuous, are the most resistant to treatment. Nevertheless, a 3-month trial of a combination of a vitamin D₃ derivative with a potent corticosteroid twice or even thrice daily application is warranted. The less nail of the nail is present, the easier is penetration of the drug to the very psoriatic lesion. Clipping the onycholytic nail over the nail bed is essential to reach nail bed psoriasis. Thinning the nail by filing or grinding, or drilling holes into the nail plate with mechanical burrs or with ablative lasers is often used to enhance nail penetration.

Corticosteroids are often used in nail psoriasis. They have to be class IV (high potency) and applied once or twice a day on the proximal nail fold in case of matrix and on the nail plate in nail bed affection. Both clobetasol and betamethasone dipropionate were tested in clinical trials and showed comparable results concerning pitting, salmon patches, subungual hyperkeratosis, and onycholysis. All high-potency steroids carry the risk of skin atrophy when used on the proximal nail fold, often associated with hypopigmentation. Whether or not using them for 4–5 days a week as a “pulse” treatment is equally effective and reduces this risk remains to be proven. Clobetasol 8% was tested as a nail lacquer with good results depending of the duration of the treatment.

Perilesional injections are another type of local treatment. This increases the concentration of the drug at the site of disease while minimizing the dose for the whole organism. Perilesional injection of corticosteroids is by far the most often performed, either by injection with a needle or by high air-pressure devices. Injection with a 30 G needle and using some distraction techniques such as vibration and pressure around the area to be injected make the procedure tolerable although some patients prefer the needle-less technique. 0.1 mL of a triamcinolone acetonide suspension (10 mg/mL) to be injected into both sides of the proximal nail fold every 6 weeks often improves nail psoriasis, but is painful and cumbersome for the patient.

Methotrexate is also used for perimatrical and nail bed injections with some success. The dose is 0.1 mL of a 25 mg/mL solution; however, this cytostatic drug may slow down nail growth and make an improvement visible only very late.

The best treatment results are those with systemic antipsoriatic therapies, including biologics.

 

Therapeutic ladder for nail psoriasis 
Key to evidence-based support: (1) prospective controlled trial; (2) retrospective study or large case series; (3) small case series or individual case reports.

 

THERAPEUTIC LADDER FOR NAIL PSORIASIS

·       Avoid trauma (3)   ·       Topical vitamin D3 analogues: calcipotriene (calcipotriol) – nail bed psoriasis (2)   ·       Topical tazarotene 0.1% gel – nail bed psoriasis (2)   ·       Topical calcipotriene plus betamethasone dipropionate ointment – nail bed psoriasis (2)   ·       Intralesional corticosteroid (e.g. 2.5–5 mg/ml triamcinolone acetonide in saline) – nail matrix psoriasis (1)   ·       Acitretin (0.2–0.3 mg/kg/day) – nail matrix and nail bed psoriasis (1)   ·       Methotrexate – if indicated for additional manifestations (2)   ·       Cyclosporine – if indicated for additional manifestations (2)   ·       Targeted immunomodulators, e.g. TNF-α inhibitors – if indicated for additional manifestations (1)

 

 

Conclusion

 

Nail involvement in psoriasis is common. It is an indicator of poor prognosis and of a higher risk to develop psoriatic arthritis. Surprisingly, nail psoriasis is only briefly mentioned in most national and European guidelines on the diagnosis and treatment of psoriasis; however, the European Nail Society is now working on recommendations for the treatment of nail psoriasis.

The many treatments available give evidence that hitherto none is the ideal therapy. Topical drugs have to fight with the difficulties to get through the nail and nail fold to the diseased structures. Injections that bring the remedy to the site of the disease process and greatly avoid systemic effects are painful and carry the risk of local side effects. Systemic drugs are often not used for isolated nail psoriasis, although this is accepted as a severe psoriasis considerably impairing quality of life. However, it is known that virtually all systemic treatments that improve the skin lesions are also beneficial for the nails, although often with a delayed and less pronounced response. The potential systemic adverse effects have to be kept in mind before and during such a therapy. The development of new biologicals has revolutionized psoriasis treatment and thus also that of ungual psoriasis. Finally, there are some physical modalities such as ionizing rays, various light qualities including photodynamic treatment, and lasers.

Many treatment possibilities may make it delicate to choose the right approach. It is certainly wise to begin with a topical antipsoriatic preparation. This has to be used for a minimum of 4–6 months before its efficacy can be evaluated. If this does not help sufficiently, a classical antipsoriatic drug such as methotrexate or cyclosporine would be the second choice while keeping in mind all potential contraindications. If the results are not satisfying a biological may be chosen. Again, there are many contraindications that have to be carefully looked for before starting such a treatment. The choice is huge now, and the treating physician has to select among TNF-α blockers, agents interfering with T-lymphocyte functions, and IL-23 and IL-17 inhibitors.