Nails in systemic disease

Nail plate and nail unit abnormalities may be helpful as diagnostic tools or as a part of the puzzle for confirmation of systemic disease. There are specific and nonspecific nail signs, which can be seen involving one or more nails, that occur simultaneously or secondary to systemic disease. Occasionally these clues can be diagnostic, while most are nonspecific reaction patterns. Nail changes occur in the nail plate as a result of nail matrix abnormalities caused by systemic disease and other systemic insults such as reactions to medications. In this article we review some of the more common nail signs that can be used to help diagnose systemic disease.     

Nail Psoriasis

Nail psoriasis is common, occurring in up to half of patients with psoriasis and in 90% of patients with psoriatic arthritis. Left untreated, it may progress to debilitating nail disease, which leads to significant functional impairment. The most common clinical signs of nail psoriasis are nail plate pitting and onycholysis. Other classical signs include oil drop discoloration, subungual hyperkeratosis, and splinter hemorrhages. The modified Nail Psoriasis Severity Index (mNAPSI) can be used to grade the severity of nail psoriasis, while the Nail Psoriasis Quality of Life Scale (NPQ10) is a questionnaire that evaluates the impact of nail psoriasis on the patient’s functional status and quality of life. Treatment of nail psoriasis should be individualized according to the patient’s preferences, severity of nail changes, and presence of skin and/or joint involvement. Both topical and intralesional therapies are safe and effective treatment modalities for nail disease, but are limited by poor adherence and pain, respectively. Systemic therapy such as oral retinoids may be considered for widespread nail disease causing significant morbidity. Among biologic agents, tumor necrosis factor-a inhibitors and T-cell-targeted therapies such as ustekinumab may be useful for refractory severe nail psoriasis.     

Observer agreement in recording the clinical signs of nail disease and the accuracy of a clinical diagnosis of fungal and non-fungal nail disease

BACKGROUND: Onychomycosis is increasing in incidence. To date, no studies have examined the detection of abnormalities of the nail apparatus, nor the accuracy of a clinical diagnosis of onychomycosis and non-fungal nail disease. OBJECTIVES: To assess the agreement between and within different groups of observers in detecting signs of nail disease, and to obtain information regarding clinical diagnostic skills. METHODS: An observational study was performed. Nine observers, including dermatologists, mycologists, general practitioners and a dermatology clinical assistant, completed a questionnaire containing 21 clinical signs of nail disease during examination of nine patients, five with onychomycosis and four with non-fungal nail disease. Observers were additionally requested to suggest the most likely underlying diagnosis for the nail dystrophy. Mean pair observer agreement values were calculated for each of the clinical signs, between all observers and within groups of observers. The chance-corrected agreement index, kappa, was determined. From the clinical diagnoses given, the positive predictive value of a diagnosis of fungal and non-fungal nail disease was calculated. RESULTS: There was substantial between-observer agreement on only three clinical signs: abnormal nails on both hands, abnormal toenails and abnormal fingernails. More specific signs of nail disease such as onycholysis elicited weaker agreement. All observers showed accuracy in making a clinical diagnosis of fungal nail disease, with a mean positive predictive value of 0.91, compared with 0.77 for non-fungal nail disease. CONCLUSIONS: Our results showed that agreement between observers, in recording signs of nail disease, was generally poor. The clinical diagnosis of onychomycosis was highly likely to be correct, suggesting that other criteria are being employed by individuals in reaching the diagnosis.     

The Red Nail – Always Benign?

Red nail is a common disorder. However, a thorough examination of the patient's nails allows one to distinguish different diseases. For example, longitudinal erythronychia may be monodactylous or polydactylous. Only the former type can show histologically Bowen's disease or an amelanotic melanoma. Among the polydactylous type, the nosologic position of the acantholytic and dyskeratotic naevus versus Darier's disease is still controversial.Acantholytic epidermolysis bullosa looks like bullous Darier's disease, and acrokeratosis of Hopf may present also red longitudinal streaks. Subungual warty dyskeratoma is rare, but other dermatoses such as lichen planus, psoriasis, mail melanoma and various tumours have to be ruled out.Finally nail involvement in amyloidosis may precede the other signs of this systemic disease.The purpose of this paper will be focused on red nails that can present principally with red lunulae, solitary longitudinal erythronychia and multiple longitudinal erythronychia. Other aspects of this feature will also be raised.     

Management of nail psoriasis

Nail involvement is estimated to affect 80–90% of patients with psoriasis at some point in their lives and is often associated with severe disease. Patients with nail involvement experience pain, functional impairment and social stigma, with significant restriction of daily activities and quality of life. Nail psoriasis is also considered a risk factor for the development of psoriatic arthritis (PsA). Management of nail psoriasis is deemed challenging and as a result, it is often left untreated by physicians. Assessing the severity of nail disease can also be difficult in clinical practice. While the Nail Psoriasis Severity Index is used widely in trials, it is time‐consuming and rarely used in the clinic, highlighting the need to develop a simplified disease severity score for nail psoriasis. All patients should be advised to keep their nails short, wear gloves for wet and dirty work, and regularly apply emollient to the nail folds and nail surface. Patients with mild nail psoriasis, without signs of severe cutaneous psoriasis or PsA, may benefit from topical treatment, while systemic treatment is indicated in patients with severe nail involvement. Evidence suggests that all anti‐tumour necrosis factor (TNF)‐α, anti‐interleukin (IL)‐17, and anti‐IL‐12/23 antibodies available for plaque psoriasis and PsA are highly effective treatments for nail psoriasis. This article aims to provide an up‐to‐date review of the therapeutic options currently available for the management of nail psoriasis in patients with or without skin psoriasis. Therapeutic options for the management of nail psoriasis in children will also be discussed.     

Treatment of inflammatory nail disorders

This article provides an updated review on diagnosis and treatment of inflammatory nail disorders including psoriasis, lichen planus, trachyonychia, and autoimmune bullous disorders. Despite the significant negative repercussion of the nail psoriasis in the quality of life of patients, treatment is often not sufficiently effective. The efficacy of topical therapies is limited to nail bed psoriasis. Intralesional corticosteroid injections are extensively utilized in nail matrix psoriasis. Systemic immunosuppressant drugs such as methotrexate and cyclosporine have shown efficacy. Biologics, particularly infliximab and etanercept, have also demonstrated high efficacy in the treatment of severe nail disease. Nail matrix lichen planus can cause nail atrophy and irreversible nail scarring and requires prompt treatment with systemic steroids. There is not gold standard therapy for trachyonychia, but in most cases the nail signs improve spontaneously and treatment is not necessary. Nail changes in pemphigus and other autoimmune disorders respond promptly to systemic therapy with steroids and immunosuppressants.     

Nails in systemic disease

Nail abnormalities secondary to systemic disease could be classified as nail abnormalities associated with systemic disease, disease of specific organ system or associated with syndromes and genodermatoses. Because nail findings are easily observable and yield valuable information, careful examination of nails could be an important diagnostic tool for a dermatologist. A brief review of the common and not so common nail changes in systemic illness is presented.     

Nail pigmentation abnormalities

Color changes of the nail unit may be innocent or may be associated with disease. Four tables provide the reader with a means of categorizing pigmentation abnormalities in the following manner: changes attributable to systemic disorders and some predominantly dermatologic conditions, changes caused by systemic drugs or ingestants, changes attributable to local agents, and changes attributable to some named nail entities.     

Psoriasis of the nail: anatomy, pathology, clinical presentation, and a review of the literature on therapy

Psoriasis is a chronic skin disease that affects millions of people throughout the world. Even though cutaneous signs and symptoms are the most common clinical manifestations, the nails can be involved in up to 50% of cases, and their involvement remains an important yet often overlooked aspect of the disease. There is a broad spectrum of nail dystrophies associated with psoriasis, ranging from the common pitting and loosening of the nail plate to the less frequent discoloration and splinter hemorrhages seen in the nail bed. This article discusses the normal anatomy and embryology of the nail unit as well as the current understanding of the pathogenesis of the disease. It also provides an extensive review of the existing literature with respect to psoriatic nail therapy. Although there have been many recent advances in the treatment of the cutaneous form of the disease-most notably in the field of immunotherapies-the options for nail psoriasis are far more limited. While a number of treatment alternatives currently exist for nail disease, the general paucity of clear evidence regarding these choices often makes it difficult to select the most efficient, safe, and optimal treatment for the patient. Even though the current literature has shown some support for the use of topical, intralesional, radiation, systemic, and combination therapies for nail psoriasis, the available studies lack sufficient power to extrapolate a standardized therapeutic regimen. Therefore, until better-documented evidence validating the treatment options emerges within the literature, clinicians and patients are left with a vague and relatively unproven approach to psoriatic nail disease.     

Treatment of common nail disorders

Treatment of nail diseases is not always easy; topical treatment is often ineffective because the nail plate is not penetrated by topical drugs, and the nail matrix is located under the proximal nail fold. The most frequent nail disorders are nail psoriasis and onychomycosis. In these cases, systemic treatment is often necessary to cure the nail changes. Systemic treatment with steroids is mandatory for patients with nail lichen planus because the disease may cause definitive destruction of the nail matrix. Environmental nail abnormalities are frequent and include nail brittleness, onycholysis, and chronic paronychia. Preventive measures should always be associated with treatment in these cases.     

Biological therapy and nail psoriasis

Nail psoriasis affects 50% of psoriasis patients and in many cases causes impairment of manual dexterity, pain, and psychologic stress. Despite the fact that about 80% of psoriatic arthritis patients have nail involvement, patients rarely receive treatment for nail disease. Because of great difficulty in drug delivery to site of action and significant toxicities of most conventional systemic therapies, treatment of nail psoriasis can be very challenging. Biological therapy for psoriasis and psoriatic arthritis is now widely used, and early evidence indicates it may have significant benefit for some patients with psoriatic nail disease. This article reviews the clinical manifestations of nail psoriasis and discusses how to use specific biologic therapies that may provide significant new treatment options for this challenging disease.     

Pediatric nail conditions

Pediatric nail findings are plentiful and can range from benign processes to the initial signs of a systemic condition. The examination of the nail is an essential part of the pediatric physical examination. The nail unit consists of the nail plate, the nail matrix, the hyponychium, the nail bed, and the surrounding nail folds. Conditions that affect the nail unit have a variety of etiologies; these include inflammatory, congenital, and hereditary conditions as well as tumors and trauma. This review describes many of the nail conditions that are seen in the pediatric population.     

Psoriasis ungueal

Nail involvement in psoriasis is common. It is seen in up to 80% of patients with psoriatic lesions and may be the only manifestation in 6% of cases. Nail psoriasis is correlated with more severe disease, characterized by earlier onset and a higher risk of psoriatic arthritis. Accordingly, it can also result in significant functional impairment and reduced quality of life. Psoriasis involving the nail matrix causes pitting, leukonychia, red lunula and nail dystrophy, while nail bed involvement causes splinter hemorrhages, onycholysis, oil spots (salmon patches), and subungual hyperkeratosis. Common evaluation tools are the Nail Psoriasis Severity Index (NAPSI), the modified NAPSI, and the f-PGA (Physician's Global Assessment of Fingernail Psoriasis). Treatment options include topical therapy, intralesional injections, and systemic and biologic agents. Treatment should therefore be assessed on an individualized basis according to the number of nails involved, the part of the nail or nails affected, and the presence of concomitant nail and/or joint involvement.     

[Translated article] Nail Psoriasis

Nail involvement in psoriasis is common. It is seen in up to 80% of patients with psoriatic lesions and may be the only manifestation in 6% of cases. Nail psoriasis is correlated with more severe disease, characterized by earlier onset and a higher risk of psoriatic arthritis. Accordingly, it can also result in significant functional impairment and reduced quality of life. Psoriasis involving the nail matrix causes pitting, leukonychia, red lunula and nail dystrophy, while nail bed involvement causes splinter hemorrhages, onycholysis, oil spots (salmon patches), and subungual hyperkeratosis. Common evaluation tools are the Nail Psoriasis Severity Index (NAPSI), the modified NAPSI, and the f-PGA (Physician's Global Assessment of Fingernail Psoriasis). Treatment options include topical therapy, intralesional injections, and systemic and biologic agents. Treatment should therefore be assessed on an individualized basis according to the number of nails involved, the part of the nail or nails affected, and the presence of concomitant nail and/or joint involvement.     

Recommendations for treatment of nail psoriasis during the COVID‐19 pandemic

The novel coronavirus disease 2019 (COVID‐19) pandemic has resulted in a paradigm shift in disease management. Since immunosuppression may cause increased susceptibility to COVID‐19, there is uncertainty as to whether systemically treated nail psoriasis patients are at increased infection risk. While specific data on nail psoriasis treatments and COVID‐19 is lacking, we present clinical trial data on rates of upper respiratory infections, nasopharyngitis, viral infection, pneumonia and overall infections. Some systemic medications and biologics are associated with increased in infections risk compared to placebo in clinical trials. However, this data should be regarded cautiously since clinical trials on nail psoriasis, particularly controlled studies, are lacking. Our recommendations may be helpful in guiding physicians managing nail psoriasis patients during the COVID‐19 pandemic.     

Toenail disorders

The nail unit provides clues to neoplasms and systemic disease. It also may be prominent as a site for fungal and bacterial infections. Primary dermatologic disorders present a broad spectrum of nail changes. The complete physician, regardless of his field, needs to be alert to the often significant manifestations of the abnormal nail as a signal to important pathology.     

Ungual lichen planus. Lichen planus of the nail

Although reports in the literature are sparse, a definite relationship exists between nail anomalies and lichen planus. Ungual lichen planus may occur without any mucocutaneous signs, as has been documented by histologic studies. It may be the initial and most important clinical manifestation of the disease process, and permanent anonychia may result unless corticosteroid therapy is initiated promptly. Increased awareness of nail involvement will result in a more frequent diagnosis and better understanding of the disorder.     

The nail in systemic diseases

Although abnormalities of the nails have been reported in different systemic disorders,most of these abnormalities are nonspecific. This article reports and discusses only those nail signs that provide the clinician with clues for the diagnosis of systemic disorders.     

Nail involvement in pemphigus vulgaris

Nail involvement in pemphigus vulgaris is relatively rare. We describe a case of severe pemphigus involving both the skin and oral mucosa in which an acute exacerbation was preceded by the onset of nail involvement of all 4 extremities. Nail involvement occurred in the form of hemorrhagic paronychia of multiple digits. Oral, cutaneous, and nail manifestations of the disease were all well controlled by systemic therapy. A review of the literature on nail involvement in pemphigus reveals that this involvement may be manifested in multiple ways, with chronic paronychia and onychomadesis being the most common. Involvement of the nail occurs most frequently either as part of the initial presentation, or just before or concurrent with a flare of pre-existing disease. Nail involvement, when it occurs, is usually present when the disease is severe. Topical therapy is insufficient, and systemic therapy is warranted. In the majority of cases, nail recovery is complete, with no residual damage.     

Nail abnormalities associated with systemic pathologies

Nail abnormalities can arise in conjunction with or as a result of systematic pathologies. These pathologies include single-organ diseases, multisystemic diseases, and drug-induced insults. Clinical signs associated with these conditions include dyschromias, vascular alterations, periungual tissue changes, textural dystrophies, contour alterations, and growth-rate alterations. The associated systemic pathologies may affect any part of the nail apparatus, including the nail matrix, the nail plate, the nail bed, the underlying vasculature, and the periungual tissues. The anatomical location and extent of damage determine the clinically manifested anomaly.