Introduction: Onychogryphosis is a nail condition characterized clinically by a thickened, curved, yellow-brown, and opaque nail plate and may result in pain, paronychia, and onychogryphosis. Methods: We performed a nested case-control study of 1,114 onychogryphosis patients and 3,423 matched controls to quantify the association between onychogryphosis and self-care limitations, chronic foot injury, dermatologic conditions, and vascular disease. Results and Conclusion: Onychogryphosis was positively associated with increased age, activity limitations (difficulty running errands alone, bathing, and concentrating), psoriasis, onychomycosis, hallux malleus, hallux valgus, peripheral vascular disease, lower extremity ulcers, venous varices, and type II diabetes mellitus. Therefore, physicians should screen patients presenting with onychogryphosis for these conditions.

© 2023 The Author(s). Published by S. Karger AG, Basel

Introduction

Onychogryphosis is a nail condition characterized clinically by hyperkeratosis and increased curvature of a distorted, opaque, and yellow-brown nail plate, resulting in a nail resembling a ram’s horn [1]. Since onychogryphosis rarely occurs congenitally, it is uncommon in children and middle-aged adults. Instead, it is far more often acquired and occurs in older adults [1–3]. Onychogryphosis may cause pain, difficulty fitting shoes and ambulating, secondary paronychias, as well as cosmetic concerns and psychosocial consequences [1, 2, 4]. Etiologies of onychogryphosis are poorly understood. They include nail trauma, dermatologic conditions (ichthyosis, pemphigus, psoriasis), infections (onychomycosis and syphilis), vascular impairment, and self-neglect such as due to immobility or failing eyesight [1, 2, 5–7]. Therefore, our objectives were to analyze for possible associations between onychogryphosis and self-care limitations, chronic foot trauma, dermatologic conditions, and vascular disease.

Materials and Methods

We performed a nested, matched, case-control study which included patients in the USA aged 18 years or older recruited to the All of Us cohort between May 6, 2018, and October 9, 2022. The All of Us Research Program is an initiative led by the National Institutes of Health to build a database of health data from one million or more participants [8]. To date, the program has recruited 372,380 participants, and the database currently includes demographic information, medical conditions, drug exposures, laboratory values, and answers to survey questions regarding lifestyle. International Classification of Diseases (ICD) and Systematized Nomenclature of Medicine (SNOMED) diagnostic codes from electronic health record data were used to identify cases of onychogryphosis (ICD10 L60.2, SNOMED 52897009), primary degenerative dementia of the Alzheimer type with senile onset (ICD10 G30.1 and F00.1, SNOMED 416975007), hallux malleus (ICD10 M20.40, SNOMED 45636002, 122481008), hallux valgus (ICD10 M20.10, M21.619, SNOMED 122480009, 415692008), psoriasis (ICD10 L40.9, SNOMED 9014002), pemphigus (ICD10 L10.9, SNOMED 65172003), syphilis (ICD10 A53.9, SNOMED 76272004), onychomycosis (ICD10 B35.1, SNOMED 414941008), venous varices (ICD10 I83.9, SNOMED 128060009), lower extremity ulcers (ICD10 L97, SNOMED 95344007), type II diabetes mellitus (ICD10 E11.9, SNOMED 44054006), and peripheral vascular disease (ICD10 I73.9, SNOMED 400047006). Patient survey data were used to collect information on stable housing concern in the previous 6 months (All of Us concept codes 1585888 and 1585887); health insurance status (concept codes 1585387 and 1585388); difficulty with dressing or bathing (concept codes 903606 and 903605); difficulty concentrating, remembering, or making decisions (concept codes 903600 and 903699); and difficulty running errands alone (concept codes 903609 and 903608). Each case of onychogryphosis was matched to three controls based on age, sex, and ethnicity using nearest neighbor propensity score matching. An unpaired t test was used to test for differences in age between the two groups, and Fisher’s exact test was used to calculate odds ratios and p values for differences in sex and race distributions between the two groups. Wald’s test applied to ordinal logistic regression was used to calculate the odds ratio and p values for the occurrence of onychogryphosis in each decade of life. Wald’s test applied to multivariate logistic regression was used to calculate odds ratios and p values between onychogryphosis and each survey answer or co-existing condition. In each regression analysis, age, sex, and race were included as covariates. The Benjamini-Hochberg procedure was applied to adjust for multiple hypothesis testing. Conditions corresponding to a false discovery rate (FDR) of less than 0.1 were considered significant.

Results

We identified 1,141 patients with onychogryphosis and 3,423 matched controls. Mean age was 67.1 years, with 53% females, and 46% non-Hispanic whites, 15% Hispanic, 33% blacks, and 5% other, which was similar between patients with onychogryphosis and controls (Table 1). Prevalence of onychogryphosis increased with each decade of life (OR 1.59 [1.53–1.65], p < 2.2E–16, Figure 1).

Table 1.

Demographic characteristics of individuals with onychogryphosis and controls matched by age, sex, and self-reported race/ethnicity

Controls (n = 3,424)Onychogryphosis (n = 1,141)p valueAge, mean (std)67.1 (11.4)67.1 (11.4)>0.99Sex at birth count (%) Male1,529 (45)511 (45)>0.99 Female1,826 (53)608 (53) Other68 (2)22 (2)Self-reported race/ethnicity count (%) Non-Hispanic white1,575 (46)524 (46)>0.99 Hispanic514 (15)171 (15) Black1,130 (33)376 (33) Other205 (5)60 (5)Fig. 1.

Onychogryphosis prevalence in the All of Us cohort by age (decade). Error bars show 95% confidence interval computed by proportion test.

There were significant associations between onychogryphosis and activity limitations, including difficulty in running errands alone (OR 2.65 [1.8–3.89], p < 1E–6), difficulty dressing or bathing (OR 2.44 [1.61–3.70], p = 2.39E–5), and difficulty concentrating, remembering, or making decisions (OR 1.84 [1.27–2.67], p = 1.18E–3). There was no significant difference between onychogryphosis patients and controls in terms of health insurance coverage, co-diagnosis of dementia, or housing instability (Table 2). Patients with onychogryphosis versus controls were more likely to have a co-diagnosis of hallux malleus (OR 8.33 [7.67–9.01], p < 1E–6) and hallux valgus (OR 3.22 [2.57–3.96], p = 4.77E–4) (Table 3). Patients with onychogryphosis versus controls were also more likely to have a co-diagnosis of onychomycosis (OR 3.69 [1.81–7.52], p = 3.17E–4) and psoriasis (OR 2.14 [1.55–2.95], p = 3.61E–6). There were no significant associations between onychogryphosis and pemphigus or syphilis (Table 4). Patients with onychogryphosis relative to controls also more often had a co-diagnosis of venous varices (OR 2.06 [1.43–2.96], p = 9.55E−5), type II diabetes mellitus (OR 7.89 [6.72–9.27], p < 1E−6), peripheral vascular disease (OR 4.51 [3.73–5.46], p < 1E−6), and lower extremity ulcers (OR 5.38 [3.46–8.73], p < 1E−6) (Table 5).

Table 2.

Association of onychogryphosis with factors that limit self-care

Controls (n = 3,424)Onychogryphosis (n = 1,141)OR (95% CI)p valueDementia<20 (<2.6)<20 (<2.6)0.359 (0.0686–1.87)0.224Unstable housing in the last 6 months464 (14)182 (16)1.22 (1.01–1.49)4.06E–02Lack of health insurance133 (4.0)44 (4.0)1.01 (0.709–1.44)0.955Difficulty running errands alone91 (2.7)49 (4.4)2.65 (1.8–3.89)7.38E–07Difficulty bathing or dressing77 (2.2)40 (3.5)2.44 (1.61–3.7)2.39E–05Difficulty concentrating, remembering, or making decisions120 (3.5)49 (4.4)1.84 (1.27–2.67)1.18E–03Table 3.

Association of onychogryphosis with foot deformity

Controls (n = 3,424)Onychogryphosis (n = 1,141)OR (95% CI)p valueHallux malleus (hammer toe deformity)95 (2.8%)221 (19%)8.55 (7.67–9.01)1.11E–72Hallux valgus (bunion)96 (2.8%)97 (8.5%)3.22 (2.57–3.96)4.77E–4Table 4.

Association of onychogryphosis with dermatologic and infectious disease

Controls (n = 3,424)Onychogryphosis (n = 1,141)OR (95% CI)p valuePsoriasis98 (2.9)67 (5.9)2.14 (1.55–2.95)3.61E–06Pemphigus<20 (<2.6)<20 (<2.6)0.134 (0.0141–1.27)7.97E–02Onychomycosis<20 (<2.6)<20 (<2.6)3.69 (1.81–7.52)3.17E–04Syphilis<20 (<2.6)<20 (<2.6)0.269 (0.11–0.659)4.07E–2Table 5.

Association of vascular disease with onychogryphosis

Controls (n = 3,424)Onychogryphosis (n = 1,141)OR (95% CI)p valueVenous varices77 (2.2%)51 (4.5%)2.06 (1.43–2.96)9.55E–05Type II diabetes mellitus401 (12%)564 (49%)7.89 (6.72–9.27)<1E–6Peripheral vascular disease247 (7.2%)287 (25%)4.51 (3.73–5.46)<1E–6Lower extremity ulcer32 (0.93%)55 (4.8%)5.38 (3.46–8.37)<1E–6Discussion

The overall prevalence of onychogryphosis is unknown, but it is relatively more common in older adults. The prevalence in older patients in hospital and long-term care settings was estimated in two studies. Nakagami et al. reported 31 cases of onychogryphosis across 171 residents with a mean age of 86 years housed in one long-term health facility and two special nursing homes in the Tokyo metropolitan area [9]. Ebrahim et al. [10] observed 38 cases of onychogryphosis among 100 patients with a mean age of 81 years in a Nottingham hospital. The condition causes considerable morbidity from pain, difficulty ambulating, acute paronychia, secondary onychomycosis, esthetic concerns, and psychosocial consequences [1, 3, 11].

The etiology of acquired onychogryphosis is poorly understood, and associations with long-standing neglect, other dermatologic diseases, nail microtrauma, and foot anomalies such as hallux valgus have been limited to case reports [1]. Galeone et al. [12] described a case of onychogryphosis resulting from long-term neglect and infrequent cutting of the nails in a 77-year-old homeless woman. Möhrenschlager et al. [2] reported one case of onychogryphosis of the left great toenail penetrating the second toe and resulting in an ulcer in a 92-year-old woman receiving home nursing care with other signs of physical neglect. Onychogryphosis has also been reported in the setting of dermatologic disease. Srivastava et al. [11] reported on 1 patient with onychogryphosis who had a history of nail psoriasis, and Silbey et al. [13] report a case of onychogryphosis of both great toenails in a patient with psoriatic arthritis. Onychogryphosis of all digits was observed by Biswas et al. [14] in a patient with the rare congenital condition ichthyosis hystrix. Cho et al. [15] reported a case of onychogryphosis in association with onychomycosis in a 90-year-old woman. Douri et al. [16] reported on one case of onychogryphosis of the right 2nd fingernail in patient with a history of paronychial cutaneous leishmaniasis.

Therefore, data on associations with onychogryphosis are tenuous at best and have not yet been quantified in a larger cohort. To address this knowledge gap, we performed a nested, matched, multi-ethnic case-control study of 4,564 patients, including 1,114 cases of onychogryphosis, which is by far the largest study on onychogryphosis to date. The mean age of patients with onychogryphosis was 67.1 years (SD 11.4), with prevalence increasing with age, which is consistent with prior reports with onychogryphosis being more common in older adults [1, 2, 17]. We found that onychogryphosis is associated with increased odds of activity limitations, affecting self-care, evidence of chronic foot trauma, psoriasis, onychomycosis, and vascular disease.

We identified a significant frequency of onychogryphosis among participants who reported difficulties concentrating, remembering, or making decisions; running errands alone; and bathing or dressing. Each of these limitations may lead to self-neglect and decreased frequency of nail cutting, promoting development of onychogryphosis. Onychogryphosis may also itself cause mobility issues, resulting in the reported activity limitations.

We also identified a significantly increased frequency of hallux malleus (hammer toe deformity) and hallux valgus (bunion) among patients with onychogryphosis relative to controls. These deformities are caused and/or exacerbated by chronic foot trauma due to improperly fitting shoes. Nail trauma may also occur in this setting and may cause onychodystrophy and onychogryphosis [1, 10, 18]. Conversely, onychogryphosis may alter foot biomechanics, leading to foot deformity [18].

In relation to dermatologic disease, we found a significant association between onychogryphosis and both psoriasis and onychomycosis. Clinically, nail psoriasis may exhibit nail plate pitting, onycholysis, splinter hemorrhages, nail bed hyperkeratosis, salmon patches, and nail plate thickening [19, 20]. Nail bed inflammation can cause subungual hyperkeratosis and nail plate thickening; such a process may also contribute to the nail plate overgrowth observed in onychogryphosis [19, 20]. Onychomycosis presents clinically with onycholysis, subungual hyperkeratosis, and nail plate thickening [21, 22], which when severe and untreated could result in onychogryphosis.

We also found that vascular disease and venous insufficiency, including peripheral vascular disease, lower extremity ulcers, type II diabetes mellitus, and venous varices, were associated with onychogryphosis. Vascularization and oxygenation are essential for normal nail keratinization, and vascular disease may impair the nail’s response to microtrauma, increasing risk of nail damage and dystrophy [23]. Vascular disease may also limit activity, resulting in self-neglect. Besides angiopathy, diabetes can also cause peripheral neuropathy and impaired wound healing. Chronic hyperglycemia also results in protein glycation, which affects collagen flexibility and keratinocyte proliferation. These factors increase risk for unrecognized nail trauma, onychomycosis, and nail plate hypertrophy, all of which may contribute to onychogryphosis [5, 24].

Though we studied a relatively large cohort of onychogryphosis cases, we were unable to quantify associations between onychogryphosis and rare conditions, such as ichthyosis, and infections that are uncommon in the USA, such as leishmaniasis. Underdiagnosis of onychogryphosis in the database is also a potential limitation. Nail education during training is often inadequate, and thus onychogryphosis may not be recognized by many physicians and even some dermatologists [25]. Diagnosis of onychogryphosis may also be an incidental finding that may be missed unless the patient’s socks and shoes are removed with a thorough inspection of the feet and nails.

While the associations described here are correlative and should not be interpreted as causal, they may affect management decisions. Onychogryphosis may be treated palliatively with footwear assessment to avoid nail trauma and with mechanical debridement of the nail plate. Alternatively, the definitive operative treatment is nail avulsion followed by partial or complete matricectomy; nail avulsion alone is associated with a high rate of recurrence [1]. The strong association between onychogryphosis and foot deformities associated with chronic injury suggests that regardless of whether operative management is chosen, care should be taken to ensure that footwear is well fitting. In elderly patients and those with activity limitations and vascular disease, conservative management may be preferable due to difficulties with postoperative wound care and healing. The strong association of onychogryphosis with activity limitations, type II diabetes, and vascular disease suggests that these conditions should also be screened for and considered when deciding management.

In summary, in this nested case-control study of 1,114 onychogryphosis patients and 4,564 controls, we found that onychogryphosis is common in older adults and identified positive associations between onychogryphosis and self-care limitations, foot deformities associated with chronic injury, psoriasis, onychomycosis, and vascular disease. These associations suggest potential etiologies for onychogryphosis and co-diagnoses for which patients with onychogryphosis should be screened for in the clinic.

Acknowledgments

This study used data collected from the All of Us Research Program, which is supported by the National Institutes of Health, Office of the Director: regional medical centers: 1 OT2 OD026549; 1 OT2 OD026554; 1 OT2 OD026557; 1 OT2 OD026556; 1 OT2 OD026550; 1 OT2 OD 026552; 1 OT2 OD026553; 1 OT2 OD026548; 1 OT2 OD026551; 1 OT2 OD026555; IAA#: AOD 16037; federally qualified health centers: HHSN 263201600085U; data and research center: 5 U2C OD023196; biobank: 1 U24 OD023121; the participant center: U24 OD023176; participant technology systems center: 1 U24 OD023163; communications and engagement: 3 OT2 OD023205; 3 OT2 OD023206; and community partners: 1 OT2 OD025277; 3 OT2 OD025315; 1 OT2 OD025337; 1 OT2 OD025276. In addition, the All of Us Research Program would not be possible without the partnership of its participants.

Statement of Ethics

This study protocol was reviewed and the need for approval was waived by Weill Cornell Medicine Human Research Compliance.

Conflict of Interest Statement

Ms. Choo has no conflicts of interest to declare. Dr. Lipner serves as a consultant for Hoth Therapeutics, BelleTorus Corporation, Ortho-dermatologic, and Moberg Pharmaceuticals.

Funding Sources

Z.C. was supported by an F30 predoctoral fellowship from the NIH/NCI (F30CA268747) and a Medical Scientist Training Program grant from the National Institute of General Medical Sciences of the National Institutes of Health under award number T32GM007739 to the Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program.

Author Contributions

Z.C. and S.L. contributed to the study design, data collection and analysis, and manuscript preparation.

Data Availability Statement

Research data at the level of individual All of Us study participants are not publicly available according to the program data distribution policies. However, individuals can apply for access to the database. Further inquiries can be directed to the corresponding author.

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