Current Concepts In Treating Psoriatic Nails

Emerging research suggests that psoriasis is a multisystem disease, a disease that may have a psychological impact as well. Accordingly, this author examines the pathogenesis and epidemiology of psoriatic nails, provides keys to the clinical diagnosis and reviews potential treatment options.

Which nail disease masquerades as onychomycosis but is actually a papulosquamous skin disorder? Psoriatic nails resemble onychomycosis and often both conditions arise simultaneously. Recognizing and treating the dual diagnoses should improve patient outcomes. Psoriatic fingernail and toenail damage can be one of the most distressing features of an already difficult to bear skin disease.

Mendez-Tovar and colleagues studied 150 patients with psoriasis and found that 45 percent had healthy nails, 28 percent had onychomycosis and 27 percent showed nail changes without fungal infection.¹ They also found that fingernail changes were more associated with psoriatic onychopathy while toenail changes were more frequently the result of fungal infection. Not surprisingly, the duration of the psoriasis increased the risk of developing onychomycosis. The authors concluded that in patients with psoriasis, fingernail disorders are mainly due to the psoriasis while toenail disorder changes can be associated with onychomycosis.  

When our own immune system attacks the most visible organ system, it is bound to leave emotional scars. Depression, anxiety, sexual dysfunction, unemployment and suicidal ideation are more prevalent in patients with psoriasis. The severity of this psychosocial impact parallels the emotional impact of cancer, heart disease, diabetes and severe depression.²

There is increased evidence to support the recognition of psoriasis as a multisystem disease. Researchers have linked many extracutaneous disorders beyond arthritis and type 2 diabetes to psoriasis.³ These diseases surprisingly include peripheral vascular disease, fatty liver disease, chronic obstructive pulmonary disease (COPD), Parkinsonism, obstructive sleep apnea and obesity. These comorbidities help account for the increased morbidity and mortality that occur in psoriatic populations. Patients with severe psoriasis are significantly more likely to die of cardiac or cerebrovascular disease. Generally, the severity of the psoriasis increases the risk of comorbidities.

In addition to increased mortality, the economic cost of living for patients with psoriasis can amount to a lifetime cost of $11,498 for the relief of physical symptoms and emotional health. The annual United States cost of psoriasis amounted to approximately $112 billion in 2013.⁴

Key Insights On The Pathogenesis And Epidemiology Of Psoriasis
Psoriasis is an inherited chronic hyperproliferative autoimmune disease that is essentially a T-cell disorder. It is a complex autoimmune inflammatory disease that occurs in genetically susceptible individuals.⁵ The critical event is dysregulation of the immune system. Recent recognition of the immune pathogenesis, in contrast to earlier concepts solely focusing on hyperproliferation, has led to new and emerging therapies that target specific immunological aspects of the disease.⁶

The first pathological event is antigenic stimulation and activation of cutaneous dendritic cells or immune processing cells. These cutaneous cells include epidermal Langerhans cells, dermal dendritic cells and plasma cells. These immune cells have a spectrum of different functions with implications that extend far beyond the skin. They have the potential to internalize particulate agents and macromolecules, and display migratory properties that endow them with the unique capacity to journey between skin and draining lymph nodes where they encounter antigen-specific T lymphocytes.⁷

The recruited T cells produce additional cytokines like interferon that stimulate keratinocytes to proliferate and produce inflammatory antimicrobial peptides and other cytokines. Interestingly, researchers have found that the mean serum levels of tumor necrosis factor alpha (TNF-a) are significantly higher in psoriatic patients with nail lesions in comparison to those without.^7,8 This evidence helps confirm the pivotal role of TNF-a in the pathogenesis of nail psoriasis and suggests that anti-TNF agents could be especially beneficial in psoriatic nail disease.

At a cellular level, all psoriasis is basically pustular with foci of neutrophils forming microabscesses. The histologic diagnosis of nail psoriasis requires the presence of neutrophils in the nail bed epithelium and in the parakeratotic fragments of the nail plate. Often, there is concurrent hyperkeratosis and parakeratosis.⁹ Interestingly, psoriatic histological criteria can overlap with the features of onychomycosis so it is prudent for the pathologist to stain with fungal-specific periodic acid Schiff (PAS) reaction in addition to standard hematoxylin and eosin staining procedures.

Nail involvement is an extremely common feature of psoriasis and affects approximately 10 to 78 percent of psoriasis patients with 5 to 10 percent of patients having isolated nail psoriasis.¹⁰ Importantly, 70 to 80 percent of patients with psoriatic arthritis have nail psoriasis.¹⁰

How To Recognize Psoriatic Nail Patterns
The specific site of the attack determines the effects of psoriasis on the nail unit. One can only understand the clinical changes on the basis of parakeratotic changes. With a hyperproliferative disorder like psoriasis, the accelerated proliferation of the skin does not allow time for the normal cell maturation process to occur. Authors have described this as the cellular march of death from basal cell to shed corneocyte.^11,12 In psoriasis, the keratinocytes remain nucleated into upper dermal and epidermal layers. This is apparent histopathologically as parakeratosis. If the parakeratosis is localized in the nail matrix, specific changes in the nail will result depending on localization and spreading in the matrix. Punctate indentations (pits) may develop. If there is a ribbon-like, square-dimensioned localization, we see streaks and ridges. If parakeratotic cells invade the whole of the matrix, the so-called psoriasis unguis crateriformis will develop.^11,12

When psoriasis attacks the proximal matrix, it also can produce trachyonychia, Beau’s lines and transverse grooves. When psoriasis attacks the distal matrix or the visible lunula, it tends to cause spots or erythematous color changes. Psoriatic mediation of inflammation of the mid or distal matrix causes leukonychia. This is due to the forming nail plate incorporating white opaque parakeratotic cells with retained nuclei. When the nail bed and hyponychium are affected, they can exhibit onycholysis, oil drops (salmon patches) or subungual hyperkeratosis. Psoriasis of the distal nail bed may manifest as splinter hemorrhages and onycholysis.

When correlating these pathological changes to clinical signs, it is helpful to recall that the keratinization of the distal matrix cells forms the ventral portion of the nail plate whereas the keratinization of the proximal matrix cells forms the dorsal portion of the nail plate.¹³ Psoriasis that happens to affect the unseen inferior side of the proximal nail fold can alter the dorsal aspect of the nail plate throughout its course.

Pits develop due to a focal psoriatic attack on the proximal nail matrix, leaving spotty clusters of immature parakeratotic keratinocytes to form white clumps that shed prematurely, leaving a clear pothole in the nail plate that has gradual distal growth. Tangential examination of the fingernails can most easily detect the clear pits.

Onycholysis is a nail unit reaction pattern to any inflammatory insult to the nail bed including psoriatic inflammation of the nail bed. In onycholysis, the nail plate appears whitish. The most common diseases producing fingernail onycholysis are psoriasis and pustular psoriasis. Once the separation occurs, the environmental flora sets up temporary colonization in the available space.¹⁴ In toenails, onycholysis is typically secondary to microtrauma from shoe pressure and trauma of mal-positioned digits impinging on the closed toe box of shoes.¹⁵

The oil drop sign or salmon-colored patch is a transparent discoloration of the nail bed. It can variously appear as yellow, brown, salmon or red circular to oval patches under the nail plate. It occurs when psoriasis involves the nail bed. The discolored patch may gradually cause semilunar onycholysis as the nail plate, no longer fixed to the nail bed, grows out.¹⁰  

According to Sandre and colleagues, when nail patients also present with joint tenderness, their nail changes tend to be more severe.¹⁶ Also, when periungual psoriasis extends over the distal interphalangeal joint, the psoriatic nail changes are associated with higher inflamed joint counts. Higher swollen joint counts are associated with more splinter hemorrhages and nail bed changes. Higher tender joint counts have also been associated with rough onychorrhexis, periungual psoriasis, red lunula and nail crumbling. The strongest association is a swollen or tender distal interphalangeal joint with subungual hyperkeratosis.¹⁶ In general, the radiographic severity mirrors nail unit changes. The rate of osteolysis is higher in the earlier disease course and more severe in those with nail dystrophy.¹⁷  

Pearls On Conducting A Thorough Workup
Dermoscopic examination of the nail unit can detect early nail involvement in psoriasis and aid in differentiating it from other nails disorders such as onychomycosis and microtraumatic nail dystrophy. Yadav and Khopkar recently described the dermoscopic features of psoriatic nails.¹⁸ They observed coarse pits, onycholysis, an oil drop sign and splinter hemorrhages in over half of the fingernails of their psoriatic patients. Particularity stout, globose, dilated, pink- to red-colored nail bed vessels arranged longitudinally at the onychodermal band were surrounded by a prominent halo. Splinter hemorrhages appeared as purple streaks.

A simple nail clip biopsy can identify signs of psoriasis, onychomycosis and chronic microtrauma. Since the rate of concurrent onychomycosis is so high, it is prudent to order a PAS reaction and Gomori’s methenamine silver stain for dermatophyte detection. If the clinical appearance is atypical, fungal cultures and polymerase chain reaction (PCR) may be helpful to refine the diagnosis. Consider radiographic examination to detect underlying psoriatic arthritis.

Addressing Treatment Challenges
The Medical Board of the National Psoriasis Foundation has developed treatment recommendations for four clinical nail psoriasis scenarios.¹⁹ Which treatment works best, it turns out, is a more difficult question to answer than one might think. In a disorder for which total cure is uncommon, we must use surrogate markers of improvement to gauge efficacy. Basically, one can measure what the patient thinks about the disease and what the treating physician observes. One can measure a patient’s view by collecting quality of life data. The Dermatology Quality of Life Index is a measurement tool of patient responses to a simple 10-question validated questionnaire pertaining to their perceptions of their dermatological disease.²⁰

Perhaps a more objective measurement of clinical severity is the Nail Psoriasis Severity Index, which summarizes the clinical changes of nail psoriasis. To highlight how difficult this assessment can be, there are at least eight different scoring systems. Recently, Jancin said at the World Congress of Dermatology that unfortunately “the last 12 randomized clinical trials used 21 different ways of scoring the results of treatment so comparing the studies means comparing apples to oranges.”²¹

Despite difficulty in study comparison, there is general agreement that for disease limited to the nails, high-potency topical corticosteroids with or without calcipotriol are initial options. Baran and Tosti first described the use of 8% clobetasol propionate (Clobex, Galderma) in a nail lacquer vehicle in the treatment of 45 patients with nail psoriasis.²² In order to help prevent the potential adverse effects of intralesional corticosteroids or corticosteroids, one can also use a nail lacquer in a cream or gel the patient can apply to the skin.Subsequent studies have confirmed favorable results with 8% clobetasol propionate lacquer, which has effective transungual penetration and a therapeutic effect both on the nail bed and matrix lesions while lacking significant side effects.²³

When topical therapy has failed in patients with more significant nail disease, authors recommend treatment with adalimumab (Humira, AbbVie), etanercept (Enbrel, Amgen), intralesional corticosteroids, ustekinumab (Stelara, Janssen Biotech), methotrexate sodium (Rasuvo, Medac Pharma) and acitretin (Soriatane, Stiefel Laboratories).²⁴ For patients with significant skin and nail disease, authors strongly recommend adalimumab, etanercept and ustekinumab. Methotrexate, acitretin, infliximab (Remicade, Janssen Biotech) and apremilast (Otezla, Celgene) are other recommendations.²⁴ Finally, for a patient with significant nail, skin and joint disease, authors recommend adalimumab, etanercept, ustekinumab, infliximab, methotrexate, apremilast and golimumab (Simponi, Janssen Biotech).²⁴

Ultraviolet B (UVB) phototherapy is a common treatment modality for psoriasis and other skin diseases. Although the combination of UVB with sensitizing psoralens has been in use for many decades, many clinicians are hesitant to use this type of phototherapy due to concern over increasing the skin cancer risk. Fortunately, a comprehensive review of over 3,400 UVB-treated patients has shown no increased skin cancer risk.²⁵ Interestingly, treatment of generalized psoriasis with methotrexate reduces the risk of death from associated cardiovascular disease.²⁵ Unfortunately, disease-modifying anti-rheumatic drugs (DMARDs) and anti-TNF therapies do not appear to prevent mutilating psoriatic arthritis from developing.¹⁶

A Guide To Topical Alternatives
Interestingly, a randomized, double-blind, placebo-controlled trial showed that a topical homeopathic lacquer containing soluble chitin was more efficacious than placebo in improving the signs of psoriatic nail dystrophies.²⁶ Also, chemical peels of cosmetically disfiguring roughened nail plates can brighten, smooth and shine with 70% glycolic acid.²⁷ Al-Mutairi and colleagues have reported significant improvement in psoriatic fingernails treated with lasers.²⁸ They compared nail severity scores with both excimer and pulsed dye lasers. The authors concluded the pulsed dye laser treatments produced generally good results. While healing takes place, gel nail cosmetic procedures can camouflage cosmetically improve disfigured nails when other treatment options have failed.^29,30 Manual and electric debridement can also provide immediate, albeit temporary improvement in symptoms and appearance.  

An important part of treatment is to ensure that the patient is avoiding all the factors that may exacerbate the disease. Patients should avoid physical trauma, thoroughly wipe the hands and feet dry, and keep the nails short.³¹ This helps reduce Koebnerization or the isomorphic response, a well-known phenomenon that can trigger the formation of new psoriatic lesions at sites of physical injury. Psoriatic changes of the nail unit can be triggered by minor traumas such as manicure, biting the nails, picking or trimming the cuticle, repetitively clearing subungual debris, or wearing tight-fitting shoes. Some drugs can make things worse. Research has shown that beta-blockers, lithium, antimalarial agents, anti-TNF and interferon can trigger severe exacerbations of psoriasis.⁵ Preparing the patients for the possible roller coaster like cycling of psoriasis can be helpful.

In Conclusion
Recognizing the clinical signs of psoriatic nail dystrophy and appreciating the psychological impact patients face are important in order to offer patients reassurance with a liberal dash of hope. Understanding the various treatment options can help patients cope with a challenging nail disorder.

Dr. Bodman is an Associate Professor at the Kent State University College of Podiatric Medicine. He is a Diplomate of the American Board of Podiatric Medicine. Dr. Bodman is in private practice in Ohio.

References

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For further reading, see “Essential Insights On Treating Psoriatic Lesions In The Lower Extremity” in the January 2012 issue of Podiatry Today.