Nail Unit Psoriasis (Nail Psoriasis)
Nail Unit Psoriasis
Are You Confident of the Diagnosis?
Characteristic findings on physical examination
Characteristic findings of nail unit psoriasis include pitting, leukonychia, red spots in the lunula, onycholysis, nail plate crumbling, onycholysis, subungual hyperkeratosis, splinter hemorrhages, and “oil drop” discoloration (
Characteristic features of nail unit psoriasis are seen, with onycholysis, splinter hemorrhages, and oil spots.
Medium-power view of a biopsy of nail unit psoriasis. This sample is from the nail bed. There is psoriasiform epithelial hyperplasia and hypergranulosis
High-power view of a biopsy of nail unit psoriasis. The epithelium demonstrates mild spongiosis and there are areas with parakeratosis with neutrophils within them.
Initial evaluation of a suspected case of nail psoriasis should include an evaluation for onychomycosis, the manner of which could be guided by physician preference. A nail clipping sent for histology utilizing a PAS stain serves this purpose well. Other options include performing a potassium hydroxide examination of the nail(s) in question, as well as fungal culture. Overlapping features in the nail unit can be seen with (but is not limited to) onychomycosis, lichen planus, and simple onycholysis. It is important to examine other areas of the body as there may be signs that another dermatosis is present, and can help guide the clinical impression to the correct diagnosis affecting the nails.
Expected results of diagnostic studies
If the diagnosis is in doubt, a nail unit biopsy is a simple way to obtain additional diagnostic information. Features of nail unit psoriasis are characteristic under the microscope. As is seen with cutaneous psoriasis, there is psoriasiform epidermal hyperplasia, parakeratosis, dilated blood vessels in the papillary dermis, and the presence of neutrophillic inflammation. However, the histopathology of nail unit psoriasis also demonstrates features which are unique to this anatomic location, and includes the presence of hypergranulosis of the epithelium (as opposed to hypogranulosis in cutaneous psoriasis), spongiosis, the presence of serum or hemorrhage in the cornified layer, and epithelial papillomatosis.
If a nail unit biopsy is performed, it is important to biopsy the area which is responsible for the clinical signs seen. For example, if pittting is the predominant clinical sign, then biopsy of the nail matrix is indicated. If the most prominent clinical feature on a particular nail unit is subungual hyperkeratosis, then the nail bed should be biopsied. Surgical approaches such as a lateral longitudinal excision can include multiple anatomic areas of the nail unit in a single biopsy specimen.
Nail psoriasis can be associated with psoriatic arthritis, so it is important to ask patients about these symptoms. Up to 50% of patients with psoriasis of the skin will also have nail unit psoriasis. Of patients who have both skin psoriasis and psoriatic arthritis, up to 80% will have associated nail unit psoriasis.
Between 1 and 5 % of patients will present with psoriasis limited to the nail units, without skin involvement. This is an unusual situation in general dermatology practice, but common in a referral nail clinic. The presence of nail unit psoriasis is correlated with psoriatic arthritis of nearby joints, so it is important to ask patients with nail unit psoriasis about joint symptoms.
Who is at Risk for Developing this Disease?
Patients who have an established diagnosis of cutaneous psoriasis are at risk of developing nail unit psoriasis. If psoriasis runs in the family, this could also be a risk factor for the deveopment of nail unit psoriasis. Those with psoriatic arthritis are at increased risk of developing nail unit psoriasis.
What is the Cause of the Disease?
Refer to the chapter on psoriasis for a complete discussion of etiology and pathophysiology. To date, distinct mechanisms causing nail psoriasis apart from those established for cutaneous psoriasis have not been elucidated. The clinical features of nail unit psorasis are caused by psoriasiform inflammation affecting different anatomic areas of the nail unit. For example, pits in the nail plate are caused by areas of parakeratosis which fall out of the superficial portion of the nail plate, which is created in the proximal matrix.
Systemic Implications and Complications
While cutaneous psoriasis has been linked to a variety of systemic manifestations, the systemic implication associated with nail unit psoriasis is psoriatic arthritis.
Treatment of nail unit psoriasis is challenging because of the unique anatomy of the nail unit, and the difficulty of topical medications penetrating the nail plate. Complicating matters is the fact that nail disorders in general are slow to respond to therapy. It can take 4 to 6 months to see changes in the fingernails, and even longer in the toenails. The patients need to be motivated to adhere to the treatment regimens.
It is important to remember that good nail care should be discussed with the patient, as such maneuvers will also help improve the nails in addition to medications. More details are below.
Treatments for nail unit psoriasis can be divided into topical therapies, intralesional steroid injections, and systemic therapies.
Treatment for nail unit psoriais should be undertaken by evaluating the disease extent of psoriasis over the cutaneous surface, and the presence or absence of psoriatic arthritis. More severe cutaneous involvement will call for therapeutic agents that will help the nails improve. Topical therapy can also be undertaken in conjuction with systemic therapies. If psoriasis is more widespread, or psoriatic arthritis is present, systemic medications can be considered.
For psoriasis limited to the nail units, topical medications (steroids, retinoids, vitamin D analogues) are a good way to start, as multiple therapies have demonstrated responses. Topical therapies will be able to improve most cases of nail unit psoriasis.
Intralesional injections of steroid (most commonly triamcinolone acetonide) takes some skill development to ensure that the injections are being placed in the correct anatomic areas of the nail unit. However, often there is patient apprehension with the procedure, and the procedure itself can be painful. Use of topical anesthetics as well as digital anesthetic blocks are options to decrease the pain. Distraction techniques with vibratory stimuli are another option, and can be a useful maneuver for children.
Systemic therapies include traditional oral medications for cutaneous psoriasis, and recent evidence also points to the success in treating nail unit psoriasis with some of the new biologic agents. If psoriasis is limited to the nail units, use of systemic medications should be reserved for cases with severe functional impairment or other severe burden considering the potential side effects of these medications.
Optimal Therapeutic Approach for this Disease
The optimal therapeutic approach would depend as described above on the extent of psoriasis disease burden. An important consideration also includes the patient’s tolerance for risk of systemic side effects from medications.
Nails affected by psoriasis will improve with therapies directed to psoriasis on other areas of the cutaneous surface. A reasonable stepwise approach would include starting with topical medications / intralesional injections. If these maneuvers do not demonstrate an acceptable response, systemic medicatons can be instituted. Specific guidelines of care or dosing of recommended regimens are not universially agreed upon, and when comparing the published studies, there are many variations in technique and time courses of the various therapies.
General good nail care should be discussed with the patient as an introduction to therapy. Trauma to the nails can cause worsening of the disease (Koebner phenomenon). It is important to keep the nails short, as long nail plates can act as a lever and transmit force to other areas of the nail unit. Accordingly, it is important to protect the nails, and not use them in place of a screwdriver or for other manual work. Damage and manipulation of the cuticle should be avoided. It is also important for patients to avoid attempting to remove subungual hyperkeratosis manually. If the nails will be exposed to gardening, wetwork, or chemicals, use of protective gloves is advised.
Aside from prescription medications, use of emollients around the nail unit can also help, as is true for psoriasis on other areas of the cutaneous surface.
Most of the studies on topical therapies are small case series and open-label studies. The most documented topical therapies for nail unit psoriasis include calcipotriol and topical steroids. An open label study on 60 patients with nail unit psoriasis used a regimen of calcipotriol cream every night, 5 times per week on the weekdays, and clobetasol propionate cream 2 times per week, on the weekends for 6 months. After this time period, for the next 6 months, the clobetasol propionate cream was used for 2 nights per week. Using this regimen, there was reduction in the mean thickness of hyperkeratosis of 72.3% in fingernails and 69.9% in toenails at 6 months.
A double-blind randomized comparative study for nail bed psoriasis compared a regimen of calcipotriol ointment (23 patients) and betamethasone dipropionate and salicylic acid ointment (21 patients) which was applied twice daily for 3 months, and 5 months for responders. After 5 months, for fingernails, the responders showed a 49.2% reduction of hyperkeratosis in the calcipotriol group and a 51.7% reduction in the betamethasone dipropionate and salicylic acid group. For toenails, by the end of the fifth month, there was a reduction of 40.7% in hyperkeratosis in the calcipotriol group and a 51.9% reduction in the betamethasone and salicylic acid group. There was no signficant difference between the treatments. Overall there was improvement in the degree of subungual hyperkeratosis in both groups.
A randomized investigator-blind actively controlled, parallel group comparison of patients with nail unit psoriasis had 32 patients complete a study comparing 0.005% calcipotriol and 0.05% betamethasone dipropionate ointment applied once daily for 12 weeks with 0.005% calcipotriol ointment applied twice daily for 12 weeks for nail unit psoriasis. There was no significant difference between the treatments, and 53% of patients from either group showed at least moderate improvement after 12 weeks. In another study, calcipotriol ointment was applied without occlusion twice daily for 3 months to the nails, and 5 months for responders in an open label case series. After 3 months, 14 patients showed significant improvement. By 5 months, two patients were completely clear.
A few studies have demonstrated the efficacy of the topical retinoid tazarotene in treating nail unit psoriasis. A study of 25 patients that completed the randomized open-label study where tazarotene 0.1% gel was applied at bedtime for 12 weeks was performed. There was a good clinical response in 19 of the 25 patients.
Another randomized double-blind vehicle-controlled parallel group study included 21 patients with nail unit psoriasis treated with tazarotene 0.1% gel and 10 patients with nail unit psoriasis treated with vehicle gel applied to a target fingernail and the surrounding nail folds once daily in the evening for up to 24 weeks. One of the target nails was occluded and the other was not.
The results showed that tazarotene was more effective than the vehicle in reducing onycholysis in occluded and nonoccluded nails. Tazarotene was more effective than the vehicle in reducing pitting in occluded nails. A study by Rigopoulos et al that compared the use of tazarotene 0.1% cream under occlusion (16 patients) with clobetasol propionate 0.05% cream under occlusion (14 patients) in patients with nail unit psoriasis showed improvement with both treatments, and there was not a signficant difference in improvement between the two treatments.
Other topical therapies have been studied, such as 5-fluorouracil, anthralin, and topical cyclosporin, but provide less evidence for efficacy, so should be considered lower as an available therapy. Topical cyclosporine or steroid nail laquers are not readily available in the United States.
Intralesional injection of steroid to different anatomic areas of the nail unit is a mainstay of therapy, although few studies have investigated its use. Triamcinolone acetonide is the most common medication employed, and it can be diluted to the desired concentration with the use of saline or anesthetic. Published studies have used concentrations including 5mg/cc and 10mg/cc. However, other sources in the literature will also describe the use of a concentration of 2.5mg/cc.
It is important to note that several studies have employed the use of a Port-o-Jet (Dermojet) device to deliver the medication, but currently, this is not favored, both because of the potential of blood splash back, and a single report of an amputation of a treated digit after development of epidermoid inclusion cysts in it. There is no standard protocol for the frequency of injections, but evaluation of the patient in particular paying attention to improvement (or lack thereof) as well as monitoring for side effects can help guide frequency. In published studies, the frequencies of injection have included a single injection without subseqent injections, weekly injections, injections every 4-6 weeks, as well as a suggestion that treatment every 3 months is probably safe with weaker concentratons over a prolonged period.
The injections should be directed to the anatomic site of the nail unit responsible for the physical sign. For example, pitting, surface ridging, and nail plate thickening are signs which originate from the matrix. Surface ridging and nail plate thickening tend to respond best to intralesional injections. Both subungal hyperkeratosis and onycholysis are caused by psoriasis affecting the nail bed. Subungal hyperkeratosis responds better than onycholysis when steroid injections are directed to the nail bed. Direct injection into the nail bed, or injection into the lateral nail folds to have the medication reach the nail bed are usually painful, so use of a proximal ring block, distal wing block, or other anesthetic preparation should be considered.
There is little evidence for the use of psoralen plus ultraviolet A (PUVA) therapy, either topicaly or orally for nail unit psoriasis, as compared to other therapies.
Systemic therapies are generally not considered for psoriasis limited to the nail units unless the involvement is severe, or the patient has failed topicals and intralesional therapy. If the patient has severe psoriasis or psoriatic arthritis, these features may guide therapy over nail-specific therapies. Topical and intralesional therapies as discussed above can be used as an adjunct to systemic therapies.
Traditional psoriatic systemic medications that have the best documented evidence to support use in nails include cyclosporine and acitretin. Cyclosporine has shown improvement with doses of 3.0 - 5 mg/kg/day. Two studies have also demonstrated improvement with acitretin at a dose of 0.52mg/kg/day and in a low dose study of 0.2 to 0.3mg/kg/day. A small study demonstrated improvement with methotrexate at a dose of 15mg per week.
Psoriatic nails have been observed in many trials of biologic agents that have been used to treat psoriasis on other areas of the cutaneous surface. Some of the trials have rigorously evaluated the extent of nail disease and response to therapy. At this time, the biologic agent which has the strongest evidence for use in nails is infliximab, a monoclonal antibody which inhibits tumor necrosis factor alpha. This agent was evaluated in the EXPRESS trial (European Inflximab (Remicade) Efficacy and Safety Study, which was randomized, double blind, and placebo controlled. This study included 378 patients with moderate to severe plaque psoriasis, and 305 of them had baseline nail involvement.
Study participants were treated with either infliximab 5 mg/kg intravenously or placebo at weeks 0,2,6, and every 8 weeks through week 46, with placebo crossover to infliximab at week 24. In the treated group, there was nail disease clearance of 6.9%, 26.2%, and 44.7% at weeks 10, 24, and 50 respectively. There was 5.1% nail clearance in the placebo group at week 24. The mean improvements in the Nail Psoriasis Severity Index (NAPSI) score at weeks 10 and 24 were 26.8% and 57.2% respectively in the treated group while in the placebo group the improvement in the NAPSI was -7.7% and -4.1% at these respective time points.
Other biologic agents which have also shown various improvements in nail psoriasis with a variety of evidence levels include alefacept, etanercept, ustekinumab, and adalimumab.
Patient monitoring will depend on the type of therapy that has been instituted. Patients using topical therapies need to be reminded that nail growth is slow, and that it can take up to 3 months to begin to see a therapeutic response. After initiating or changing a topical therapy, routine follow up should be at least 1 month. Follow up in 4-6 weeks is reasonable for patients receiving intralesional injections. Patients on systemic medications will require laboratory monitoring and follow-up visits based on the medication they are taking.
The nails take more time to demonstrate improvement than psoriasis on other areas of the skin, so too frequent a follow-up may give the impression that a particular therapeutic intervention is not working, when simply it may require more time to demonstrate a benefit. It is reasonable to continue a particular topical therapy or intralesional injections on the fingernails for about 6 months before considering a therapeutic failure. It is also important to inquire about patient compliance with the medications; when day-to-day changes are not apparent, patients may become less diligent about applying topical medications.
Unusual Clinical Scenarios to Consider in Patient Management
Nail unit psoriasis may unusually present as trachonychia or with onycholysis alone. If this is the case, a nail unit biopsy may be required to secure the diagnosis or to obtain addtional diagnostic information in a patient who is not responding to therapy.
What is the Evidence?
Rigopoulos, D, Ioannides, D, Prastitis, N, Katsambas, A. "Nail psoriasis: a combined treatment using calcipotriol cream and clobetasol propionate cream". Acta Derm Venerol. vol. 82. 2002. pp. 140.(Sixty patients with nail unit psoriasis completed an open-label study using a combination of calcipotriol cream and clobetasol propionate cream, demonstrating improvement.)
Tosti, A, Piraccini, BM, Cameli, N, Kokely, F, Plozzer, C, Cannata, GE, Benelli, C. " Calcipotriol ointment in nail psoriasis: a controlled double blind comparison with betamethasone dipropionate and salicylic acid". Br J Dermatol. vol. 139. 1998. pp. 655-9.(Improvement was seen in nail bed psoriasis with both the calcipotriol and betamethasone dipropionate and salicylic acid groups. There was no significant difference between the treatments. In the calcipotriol group, 23 patients completed the study, and in the betamethasone dipropionate and salicylic acid group, 21 patients completed the study.)
Tzung, TY, Chen, CY, Yang, CY, Lo, PY, Chen, YH. " Calcipotriol used as a monotherapy of combination therapy with betamethasone dipropionate in the treatment of nail psoriasis". Acta Derm Venerol . vol. 88. 2008. pp. 279-80.(Thirty-two patients with nail unit psoriasis completed a randomized, investigator-blind, actively controlled, parallel-group comparison study using either 0.005% calcipotriol and 0.05% betamethasone dipropionate ointment applied once daily for 12 weeks or 0.005% calcipotriol ointment applied twice daily for 12 weeks. More than half of participants from either group demonstrated at least moderate improvement after 12 weeks. There was no significant difference between the treatments.)
Zakeri, M, Valikhani, M, Mortazavi, H, Barzegari, M. "Topical calcipotriol therapy in nail psoriasis: a study of 24 cases". Dermatol Online J. vol. 11. 2005. pp. 5.(Twenty-four patients were treated with topical calcipotriol, twice daily without occlusion for 3 months. Responders were treated with 2 additional months of therapy. After 3 months of therapy, 14 patients showed significant clinical improvement.)
Bianchi, L, Soda, R, Diluvio, L, Chimenti, S. "Tazarotene 0.1% gel for psoriasis of the fingernails and toenails: an open, prospective study". Br J Dermatol. vol. 149. 2003. pp. 207-9.(Twenty-five patients with nail unit psoriasis completed a randomized open-label study where tazarotene 0.1% gel was applied to the nails at bedtime for 12 weeks. Nineteen of the 25 patients showed a good clinical response.)
Scher, RK, Stiller, M, Zhu, YI. "Tazarotene 0.1% gel in the treatment of fingernail psoriasis: a double-blind, randomized, vehicle-controlled study". Cutis. vol. 68. 2001. pp. 355-8.(This double-blind, randomized vehicle controlled study followed patients with nail unit psoriasis treated with either tazarotene 0.1% gel or vehicle. Tazarotene was more effective than the vehicle in reducing onycholysis in occluded nails and nonoccluded nails. It was more effective than vehicle in reducing pitting in occluded nails.)
Rigopoulos, D, Gregoriou, S, Katsambas, A. "Treatment of psoriatic nails with tazarotene cream 0.1% vs. clobetasol propionate 0.05% cream: a double-blind study". Acta Derm Venereol. vol. 87. 2007. pp. 167-8.(In this randomized, double-blind study treating nail unit psoriasis, 16 patients were treated with tazarotene 0.1% cream, and 14 patients were treated with clobetasol propionate 0.05% cream to the affected nail plates, surrounding nail folds and periungual skin under occlusion at bedtime for 12 weeks. Both treatments demonstrated improvement in pitting, onycholysis, hyperkeratosis, and salmon patches.)
Langley, R, Dauden, E. "Treatment and management of psoriasis with nail involvement: a focus on biologic therapy". Dermatology. vol. 221. 2010. pp. 29-42.(A comprehensive review of therapies in nail psoriasis with current information regarding biologic therapy.)
Jiaravuthisan, M, Sasseville, D, Vender, R, Murphy, F, Muhn, C. "Psoriasis of the nail: Anatomy, pathology, clinical presentation, and a review of the literature on therapy". J Am Acad Dermatol. vol. 57. 2007. pp. 1-27.(A comprehensive review of both the clinical features of and therapy for nail unit psoriaisis, as well as the pathophysiology.)
de Berker, D. "Management of psoriatic nail disease". Semin Cutan Med Surg. vol. 28. 2009. pp. 39-43.(A comprehensive review of the variety of treatment options for nail unit psoriasis.)
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