{"id":10802,"date":"2025-03-10T06:00:00","date_gmt":"2025-03-10T10:00:00","guid":{"rendered":"https:\/\/cov19longhaulfoundation.org\/?p=10802"},"modified":"2024-11-26T09:29:08","modified_gmt":"2024-11-26T14:29:08","slug":"nails-and-covid%e2%80%9019-a-comprehensive-review-of-clinical-findings-and-treatment","status":"publish","type":"post","link":"https:\/\/cov19longhaulfoundation.org\/?p=10802","title":{"rendered":"Nails and COVID\u201019 \u2013 A comprehensive review of clinical findings and treatment"},"content":{"rendered":"\n

Uwe Wollina 1,\u2709<\/sup>, Jean Kanitakis 2<\/sup>, Robert Baran 3<\/sup>, PMCID: PMC8420555  PMID: 34398500<\/a><\/p>\n\n\n\n

<\/a>Abstract<\/h2>\n\n\n\n

The SARS\u2010CoV\u20102 infection, responsible for COVID\u201019, has raised the interest for infection\u2010associated muco\u2010cutaneous symptoms. While dermatologic symptoms in general gained an increasing awareness, affection of the nail organ has been mentioned only recently. We provide a narrative review on COVID\u201019 manifestation on the nail organ and add symptoms induced by personal protective measures and SARS\u2010CoV\u20102 vaccination. Available treatment options are discussed.<\/p>\n\n\n\n

Keywords:<\/strong> COVID\u201019, COVID\u2010vaccination, nail diseases, nail organ, protective measures, SARS\u2010CoV\u20102, treatment<\/p>\n\n\n\n

<\/a>1. INTRODUCTION<\/h2>\n\n\n\n

In 2019, a new highly contagious viral disease emerged in China. Severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) was identified as the responsible pathogen and the disease was termed coronavirus disease\u201019 (COVID\u201019). On March 11, 2020, the WHO declared COVID\u201019 as a pandemic disease. 1<\/sup> <\/a>Cardiovascular and pulmonary symptoms were major clinical symptoms, but soon it was observed that the systemic nature of this infection could affect all organs and tissues of the human body. Although cutaneous manifestations have only rarely been mentioned in the early reports from Wuhan, China, they gained increasing attention later when the pandemic affected Europe and America. 2<\/sup> <\/a>The dermatological signs of this systemic infection have been now categorized and have obtained a much better awareness. 3<\/sup> <\/a>, 4<\/sup> <\/a>, 5<\/sup> <\/a>, 6<\/sup><\/a><\/p>\n\n\n\n

In contrast to this, nail changes have only recently been identified as possible consequences of SARS\u2010CoV\u20102\u2010infection. 7<\/sup> <\/a>We here review the current knowledge on this topic compared with that of 2020 and added treatment options for the various nail pathologies.<\/p>\n\n\n\n

<\/a>2. NAIL CHANGES INDUCED BY SARS\u2010COV\u20102 INFECTION<\/h2>\n\n\n\n

2.1. Microvascular disturbances<\/h3>\n\n\n\n

Microvascular disturbances caused by SARS\u2010CoV\u20102 can be observed by nailfold capillaroscopy. In an open trial with 82 COVID\u201019 patients from Italy, pericapillary edema (80.5%), enlarged capillaries (61.0%), and sludge flow (53.7%) was reported. In addition, meandering capillaries and reduced capillary density has been observed in every second patient. Acute COVID\u201019 infection was associated with a higher prevalence of hemosiderin deposits resulting from micro\u2010hemorrhages and micro\u2010thrombosis. Patients who recovered from COVID\u201019 had a higher prevalence of capillary pathologies such as enlarged capillaries, meandering capillaries, loss of capillaries, and empty dermal papillae. 8<\/sup><\/a><\/p>\n\n\n\n

2.2. COVID\u2010toe or \u2010finger<\/h3>\n\n\n\n

Kanitakis et al. (2020) studied 17 patients with suspected but unconfirmed SARS\u2010CoV\u20102 infection and pernio\u2010like acral lesions. Histopathological findings of skin biopsies included deep horizontal parakeratosis (71%), necrosis of epidermal keratinocytes (41.5%), dispersed or confluents basal cell vacuolation (18%), spongiosis (12%), lymphocytic exocytosis (12%), dermal edema (76.5%), perivascular dermal lymphocytic infiltrate (100%), perivascular eosinophils (23.5%), endothelial cell swelling (65%), dermal mucin deposits (41.5%), microthrombi in superficial capillaries (12%) or venules (6%), dermal fibrin deposits (12%), and fibrin deposits in venule walls (18%). The dermal infiltrate consisted mainly of CD3+<\/sup> lymphocytes, but rare B\u2010lymphocytes or plasma cells and rare activated CD30+<\/sup> cells were intermingled. Direct immunofluorescence was positive in 82% of samples with vascular deposits of IgM (53%), IgA, and\/ or C3 (29% each) (Figures 2<\/a>, 3<\/a>, 4<\/a>). 10<\/sup><\/a><\/p>\n\n\n\n

\"FIGURE<\/a>
Pernio\u2010like lesion (\u201cCOVID\u2010toe\u201d). Scanning magnification shows upper dermal edema and a dense, mononuclear cell perivascular, and periadnexal dermal infiltration (hematoxylin\u2013eosin, original magnification \u00d740)<\/figcaption><\/figure>\n\n\n\n
\"FIGURE<\/a>
Pernio\u2010like lesion (\u201cCOVID\u2010toe\u201d). Dense dermal perivascular and periadnexal lymphocytic infiltration (hematoxylin\u2013eosin, original magnification \u00d7100)<\/figcaption><\/figure>\n\n\n\n
\"FIGURE<\/a>
Pernio\u2010like lesion (\u201cCOVID\u2010toe\u201d). Dense lymphocytic perivascular lymphocytic infiltration. Mild swelling of endothelial cells is seen (hematoxylin\u2013eosin, original magnification \u00d7250)<\/figcaption><\/figure>\n\n\n\n

In another study of 17 adolescents (median age 13.2\u2009years), 16 (94.1%) had bilaterally localized distal erythematous or cyanotic lesions. Dermatoscopy discovered red dots (100%), white rosettes (68.8%), and white streaks (62.5%). Histology demonstrated a remodeling of dermal blood vessels with a lobular arrangement, vascular wall thickening, and a mild perivascular lymphocytic infiltrate. In these patients, a SARS\u2010CoV\u20102 infection was excluded by in situ hybridization and serologic testing. 11<\/sup><\/a><\/p>\n\n\n\n

Thirty\u2010three patients (mean age 23.4\u2009years) with chilblains during the COVD\u201019 pandemic presented with erythematous and purpuric papules on the toes or fingers with edema and pruritus or burning sensation. Histology (n<\/em> = 5) revealed superficial dermal lymphocytic infiltrates around vessels and eccrine sweat glands. None of these patients tested positive with two different antibody assays for SARS\u2010CoV\u20102. 12<\/sup><\/a><\/p>\n\n\n\n

These findings question a causative relationship to SARS\u2010CoV\u20102 infection, while other studies claimed the presence of SARS\u2010CoV\u20102 spike proteins within blood endothelial cells and eccrine sweat glands. About 50% of patients with COVID\u2010toes or \u2010fingers were positive for SARS\u2010CoV\u20102. Most patients were young. 13<\/sup> <\/a>, 14<\/sup><\/a><\/p>\n\n\n\n

The serologic negativity in patients with COVID\u2010toes or \u2010fingers might be due to a later seroconversion in milder cases, limited antibody production, or induction of an early robust innate immune response to SARS\u2010CoV\u20102. 15<\/sup> <\/a>The presence of microthrombi in COVID\u2010toes and \u2010fingers suggests an association with the observed coagulopathy in COVID\u201019. 10<\/sup> <\/a>, 16<\/sup><\/a><\/p>\n\n\n\n

The most important differential diagnoses include frostbites (perniones) and chilblain lupus erythematosus. In familial chilblain lupus, loss\u2010of\u2010function mutations in the nucleases TREX1 or SAMHD1 have been identified characteristic of a type I interferonopathy. 17<\/sup><\/a><\/p>\n\n\n\n

2.3. Acral gangrene<\/h3>\n\n\n\n

A rare but severe symptom is acral gangrene (Figure 5<\/a>). It is a red flag sign of acute severe infection with multisystemic inflammation and cardiovascular malfunction. 18<\/sup><\/a><\/p>\n\n\n\n

\"FIGURE<\/a>
Acral purpuric\/necrotic lesion from a patient with severe COVID\u201019 infection. Thrombotic vasculopathy, dermal hemorrhage, and epidermal ischemic necrosis are seen (hematoxylin\u2013eosin, original magnification \u00d7250)<\/figcaption><\/figure>\n\n\n\n

2.3.1. Treatment of microvascular symptoms<\/h4>\n\n\n\n

In case of young asymptomatic patients or patients without confirmation of SARS\u2010CoV\u20102 infection COVID\u2010toe or finger is self\u2010limited and spontaneous resolution has been observed within 2\u20133\u2009weeks. The basic treatment in early COVID\u201019 stages consists of a combination of antiviral therapies (e.g., favipiravir, remdesivir, hydroxychloroquine, lopinavir plus ritonavir) with antithrombotic treatment, while in later advanced stages of the disease antithrombotic therapy should be combined with a treatment of the cytokine storm (e.g., tocilizumab, dexamethasone, interleukin\u20101 or tumor necrosis factor\u2010beta antagonists). Antithrombotic treatment is using low\u2010molecular weight heparinoids or heparin. Heparin is capable of limiting endothelial damage such as glycocalyx shedding. These compounds have anticoagulant, antiviral, and anti\u2010inflammatory effects. 19<\/sup> <\/a>Oral corticosteroids in combination with low\u2010dose acetylsalicylic acid are the treatment of choice for cryofibrinogenemia. 20<\/sup><\/a><\/p>\n\n\n\n

2.4. Periungual desquamation<\/h3>\n\n\n\n

Periungual desquamation has been reported in children with severe Kawasaki\u2010like multisystemic inflammatory syndrome (MIS\u2010C) and adults recovering from severe COVID\u201019. 21<\/sup> <\/a>, 22<\/sup> <\/a>Since coronary artery lesions have been observed in MIS\u2010C, it has been recommended to assess patients with severe COVID\u201019 for such vascular symptoms. 23<\/sup><\/a><\/p>\n\n\n\n

2.4.1. Treatment<\/h4>\n\n\n\n

Moisturizers can be used to limit the symptoms.<\/p>\n\n\n\n

2.5. Beau’s lines and onychomadesis<\/h3>\n\n\n\n

Beau’s lines are transverse grooves of the nails resulting from suppressed growth of the nail matrix by drugs or systemic infectious diseases. Beau’s lines have been observed among children and adults with COVID\u201019. 24<\/sup> <\/a>, 25<\/sup> <\/a>, 26<\/sup> <\/a>Single or multiple nails may be affected\u2013mostly fingernails. Beau’s lines can be accompanied by leukonychia. 24<\/sup><\/a><\/p>\n\n\n\n

Beau’s lines may precede onychomadesis, characterized by separation of the nail plate from the nail matrix, with persistent attachment to the nail bed. Onychomadesis is a possible consequence of COVID\u201019. 27<\/sup> <\/a>, 28<\/sup><\/a><\/p>\n\n\n\n

Another late manifestation of COVID\u201019 disease is a heterogeneous red\u2013white discoloration of the nail bed with distal onycholysis. 29<\/sup><\/a><\/p>\n\n\n\n

2.5.1. Treatment<\/h4>\n\n\n\n

Onychomadesis and Beau’s lines are usually mild and self\u2010limited. In chemotherapy\u2010induced onychomadesis, high\u2010energy 633\u2009nm red light (126\u2009J\/cm2<\/sup> for 20\u2009min every day) has been successful for fingernails but not toenails. 30<\/sup><\/a><\/p>\n\n\n\n

2.6. Discolorations of the lunula and the nail plate<\/h3>\n\n\n\n

A red\u2010violet band surrounding the distal margin of the nail lunula, is known as red half\u2010moon sign and has been observed in acute SARS\u2010CoV\u20102 infection in adult patients. 31<\/sup> <\/a>, 32<\/sup><\/a><\/p>\n\n\n\n

Distal orange discolorations of the nail plates have been reported as a delayed response several weeks after COVID\u201019 disease in elderly patients who developed later sarcopenia and anemia. 33<\/sup><\/a><\/p>\n\n\n\n

Nonblanchable transverse leukonychia (transverse white lines) was observed in a 47\u2010year\u2010old man with COVID\u201019. These lines are due to abnormal keratinization of the nail plate. 34<\/sup><\/a><\/p>\n\n\n\n

2.6.1. Treatment of discolorations<\/h4>\n\n\n\n

There is no specific treatment of nail plate discolorations. It is most important to exclude infections (onychomycosis or bacterial infections). Colored nail lacquers can cover the symptoms. Transverse white lines may be persistent after severe damage of nail matrix.<\/p>\n\n\n\n

2.7. Nail changes induced by COVID\u201019 treatments<\/h3>\n\n\n\n

Favipiravir is a purine nucleoside precursor and competitive inhibitor of RNA\u2010dependent RNA polymerase. It is used in COVID\u201019 off\u2010label with variable results. A yellow\u2010white fluorescence<\/em> on the nails has been reported as an adverse event of favipiravir used for COVID\u201019 disease. 35<\/sup><\/a><\/p>\n\n\n\n

Some patients on favipiravir developed a greenish fluorescence<\/em> in the lunula and nail plate portion near the proximal nail fold. Green fluorescence has also been observed on the scalp hair made visible by Wood’s lamp illumination. It is not yet clear, whether the fluorescence is mainly caused by drug metabolites or by additives of the tablets, such as yellow ferric oxide. 36<\/sup><\/a><\/p>\n\n\n\n

Hydroxychloroquine is an antimalarial drug with anti\u2010viral activity in vitro that may cause hyperpigmentation of tissues. Hydroxychloroquine has been widely used in prevention and treatment of SARS\u2010CoV\u20102 infection but sound evidence for a clinical benefit is lacking. Hydroxychloroquine\u2010induced longitudinal melanonychia<\/em> is a possible adverse event. 37<\/sup><\/a><\/p>\n\n\n\n

The most important differential diagnosis of drug\u2010induced melanonychia is subungual melanoma, which warrants a nail biopsy. 38<\/sup><\/a><\/p>\n\n\n\n

2.7.1. Treatment<\/h4>\n\n\n\n

Drug\u2010induced nail changes will most often spontaneously disappear after withdrawal of the responsible drug. No specific treatment exists.<\/p>\n\n\n\n

2.8. Nail changes induced by vaccination<\/h3>\n\n\n\n

Recently, some cases of pernio\u2010like lesions were reported that developed on the hands and\/ or feet a few days after vaccination against COVID\u201019 with RNA\u2010based vaccines (BionTec\/ Pfizer, Moderna). 39<\/sup> <\/a>, 40<\/sup> <\/a>, 41<\/sup> <\/a>, 42<\/sup> <\/a>Histologic examination revealed findings indistinguishable from idiopathic and COVID\u201019\u2010related perniones. 40<\/sup> <\/a>, 42<\/sup><\/a><\/p>\n\n\n\n

2.8.1. Treatment<\/h4>\n\n\n\n

Low\u2010dose acetylsalicylic acid with oral corticosteroids can be used in symptomatic and painful lesions. Due to temporary character of the vaccine\u2010induced perniones, often treatment is unnecessary.<\/p>\n\n\n\n

2.9. Nail changes by protective measures<\/h3>\n\n\n\n

The green nail syndrome or Goldman\u2010Fox syndrome<\/em> is caused by nail infection or colonization with P. aeruginosa<\/em>. It is known as an occupational disease in health care workers, especially in intensive care units. Green nail syndrome has recently been reported in health care workers during the COVID\u201019 pandemic (Figure 6<\/a>). 43<\/sup> <\/a>, 44<\/sup><\/a><\/p>\n\n\n\n

2.9.1. Treatment<\/h4>\n\n\n\n

Treatment consists of oral ciprofloxacin. Topical treatment includes removal of the onycholytic part of the nail and brushing of the nail bed with 2% sodium hypochlorite solution twice daily for at least 6\u2009weeks, and topical nadifloxacin, tobramycin, or gentamycin. 43<\/sup> <\/a>, 45<\/sup><\/a><\/p>\n\n\n\n

Irritant hand dermatitis has been observed more frequently during the COVID\u201019 pandemic especially on health care workers on COVID\u201019 departments. One study reported adverse cutaneous reactions to frequent hand washing and frequent use of disinfectants in up to 80.2%. 46<\/sup> <\/a>Nails can be affected due to wet work leading to brittle nails. Loss of cuticle is often seen together with a chronic irritant proximal nail fold dermatitis (Figure 5<\/a>). 47<\/sup><\/a><\/p>\n\n\n\n

Recommendations of skin care have been developed by various medical bodies including the European academy of dermatology and venereology task force on contact dermatitis to avoid adverse effects of sanitary procedures on hands and nails. 46<\/sup> <\/a>Limitation of wet work, use of protective gloves, and regular use of moisturizers during the day and emollients overnight are helpful.<\/p>\n\n\n\n

<\/a>3. CONCLUSIONS<\/h2>\n\n\n\n

Affection of the nail by COVID\u201019 has only recently been reported. The nail organ can be affected by SARS\u2010CoV\u20102 infection in a number of ways. Some of these symptoms are indicators of a mild course like COVID\u2010toe or\u2010finger, while others are a red flag for a serious course like acro\u2010ulcerative lesions. The medical treatment of COVID\u201019 may also interfere with the nail organ often with color changes of the nail plate. Vaccination with RNA\u2010based vaccines can induce pernio\u2010like acral lesions of digits. Prolonged use of protective gloves and wet work bear a risk for bacterial infection of the nail plate with Pseudomonas<\/em> leading to chloronychia. Health care staff with chloronychia is a potential source of transmissible infections, especially in intensive care units, transplant centers, and hemato\u2010oncology departments.<\/p>\n","protected":false},"excerpt":{"rendered":"

Uwe Wollina 1,\u2709, Jean Kanitakis 2, Robert Baran 3, PMCID: PMC8420555  PMID: 34398500 Abstract The SARS\u2010CoV\u20102 infection, responsible for COVID\u201019, has raised the interest for infection\u2010associated muco\u2010cutaneous symptoms. While dermatologic symptoms in general gained an increasing awareness, […]<\/p>\n","protected":false},"author":2,"featured_media":10886,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1148,34,779,1145,176,1143,913,533,1144,585],"tags":[],"class_list":["post-10802","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-acral-gangrene","category-atopic-dermatitis","category-dermatosis","category-finger-nail","category-fingers","category-onycholysis","category-pernio-lesions","category-skin-dermatology","category-toe-nail","category-toes"],"_links":{"self":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/posts\/10802","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=10802"}],"version-history":[{"count":3,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/posts\/10802\/revisions"}],"predecessor-version":[{"id":10912,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/posts\/10802\/revisions\/10912"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/media\/10886"}],"wp:attachment":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=10802"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=10802"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=10802"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}