Muehrcke Lines of the Fingernails

Updated: Apr 12, 2021

Author: Robert A Schwartz, MD, MPH; Chief Editor: Dirk M Elston, MD

Overview

Background

Muehrcke lines are paired, white, transverse lines that signify an abnormality in the vascular bed of the nail. Muehrcke first described paired, narrow, white, transverse fingernail lines in a series of 65 patients with severe, chronic hypoalbuminemia.[1] He believed that the lines, as shown in the image below, were a specific sign of this single biochemical alteration. Others described patients receiving multiple cytostatic agents.[2] These nail alterations may also represent an example of chemotherapy-induced nail changes. Muehrcke lines represent a type of apparent rather than true leukonychia, as they involve abnormal nail bed vasculature, which alters nail plate translucency. The whiteness becomes unapparent with pressure and is not modified by nail growth.[3] Note the image below.

Close-up view of 4 fingers. White horizontal bands are evident.

Transverse white lines of the nails occur with many different etiologies. They have been shown to occur in association with several conditions, including pellagra,[4] Hodgkin disease,[5] renal failure,[6] sickle cell anemia, or nail damage from paraquat.[7] See Pellagra, Hodgkin Disease, Acute Renal Failure, Chronic Renal Failure, and Sickle Cell Anemia for more information on these topics.

Transverse white bands appearing in the nail plate are often caused by trauma to the more proximal matrix in the area of the proximal nail fold; however, some bands, such as Mees lines and Muehrcke lines, are associated with systemic disease. The systemic disease–associated lines typically span the entire breadth of the nail bed or the nail plate, and they tend to be more homogeneous, to have smoother borders, and to occur on several nails at once.[8] Trauma-induced transverse white bands tend to be more linear, they resemble the contour of the proximal nail fold, and they usually do not spread across the entire breadth of the nail plate, whereas systemic disease–associated lines typically have a contour similar to the distal lunula and a rounded distal edge. Usually, a correlation between the onset of the bands and a systemic insult exists; a history of physical trauma to the cuticle area is not likely.[8]

Pathophysiology

The appearance of the paired, narrow, white bands on the fingernails is typically correlated with a serum albumin level below 2.2 g/100 mL. The lines have been shown to persist with chronic hypoalbuminemia and to disappear when the serum albumin level rises above 2.2 g/100 mL.[1] The exact pathogenesis has not been sufficiently articulated. A localized edematous state in the nail bed may exert pressure on the underlying vasculature, thereby decreasing the normal erythema typically seen through the nail plate.[8]

Muehrcke[1] observed the fingernails of 250 healthy adults, 500 patients with serum albumin levels in the reference range (values < 4 g/100 mL were taken as abnormal), 31 patients with nephrotic syndrome, and another 34 patients with hypoalbuminemia from other causes. The paired, white bands were not found in any healthy subjects or in patients with serum albumin levels of greater than 2.2 g/100 mL. Of the 31 patients with nephrotic syndrome, 23 (74%) had paired, transverse, white bands. Of the other 34 patients with hypoalbuminemia, 9 had serum albumin levels of less than 2.3 g/100 mL, 8 of whom developed the white bands. In 1 patient with a serum albumin level of 2 g/100 mL, the bands did not develop; however, her albumin level had decreased from 2.7/100 mL in the previous 2 weeks. The bands were more prominent in patients with albumin levels of less than 1.8 g/100 mL for at least 4 months.

Reporting on the reliability of Muehrcke lines as a sign of hypoalbuminemia, Conn and Smith[9] observed the development of transverse, white bands in 10 patients, all of whom had serum albumin values of less than 2.7 g/100 mL. Muehrcke lines were present in 10 (23%) of 44 patients with low albumin levels and with a variety of debilitating illnesses, but the lines were not observed in any patients with normal albumin levels.

More recently, Nabai[10] reported the appearance of white bands on the nails of a patient with hypoalbuminemia who had undergone a heart transplant. A month after the surgery, certain features of Muehrcke lines were noticed on both thumbnails and subsequently on other fingernails; the albumin level was reported at 3.6 g/mL. Even after the albumin levels returned to the reference range, the bands lasted for another 2 months.

Although these changes in the nails apparently resembled Muehrcke lines, features of the presentation differed from Muehrcke's original description. Muehrcke lines typically appear on the second, third, and fourth fingers; however, in this case, the bands appeared on all of the fingers in addition to the toenails (the bands were more pronounced on the fingernails). Additionally, the lines appeared and persisted at albumin levels of greater than 3.4 g/100 mL compared with levels of less than or equal to 2.2 g/100 mL as described by Muehrcke.[10] This case was the first report of transverse, white bands in a patient with a heart transplant.

Dermatologic manifestations of an obscure nature, such as nail dystrophy or nail pigmentation, have also been noted after cancer chemotherapy. Specifically, transverse, pigmented banding has been associated with certain chemotherapeutic agents. Doxorubicin is postulated to increase local melanogenesis at the nail matrix, nail plate, or nail bed.[11, 12, 13] Other agents inducing pigmented bands in nails include bleomycin,[14, 15] fluorouracil,[16, 17, 18, 19] cyclophosphamide,[20, 21] and daunorubicin hydrochloride.[22]

Physicians have reported nail changes with different combinations of drugs used in the treatment of a broad spectrum of cancers. Therefore, the nail changes do not seem to be associated with any one particular drug or drug combination. Reports also exist of patients receiving multiple chemotherapeutic agents[23] in whom the characteristic nail changes associated with Muehrcke lines were seen with slightly decreased serum albumin levels.[2] A patient was described with both longitudinal melanonychia and Muehrcke lines after chemotherapy.[24]

In 1976, Nixon[25] described a patient with a glioblastoma who was receiving therapy with procarbazine hydrochloride, vincristine sulfate, and carmustine; this patient subsequently developed broad, white bands on the proximal half of the nails after 3 months. According to Nixon,[25] transverse pigmented bands are the more common nail alteration seen with cancer chemotherapy, and these changes are not associated with the changes in the nails seen with systemic disease.

Schwartz and Vickerman[2] reported the appearance of paired, white, transverse lines on the nails of a woman with squamous cell carcinoma of the left main-stem bronchus. She was treated with a combination of platinum, doxorubicin hydrochloride, vincristine sulfate, and methyl cyclohexylchloroethylnitrosurea (CCNU). Schwartz and Vickerman[2] referred to these bands as Muehrcke lines; however, as they pointed out, the woman did not have persistent hypoalbuminemia. Within 1 day of the patient noticing 2 transverse, narrow, paired, white bands on each fingernail, her serum albumin level was at 3.4 g/dL (reference range, 3.5-5 g/dL). Evidently, chemotherapy and possibly other conditions should be considered as potential causes of paired, transverse, pigmented bands on the fingernails.

In 1983, James and Odom[26] reported a case of a 75-year-old woman who developed horizontal bands on all 10 fingernails while being treated with a combination of cyclophosphamide, doxorubicin hydrochloride, and vincristine sulfate for histiocytic lymphoma. On each fingernail (toenails were not involved), 3 bands (1-2 mm wide) with regular borders traversed each nail. The bands were white, and a 1-mm strip of normal pink nail separated the bands from each other. The patient's serum albumin level was in the reference range, and renal function was normal.[26]

Etiology

Several disease states that cause hypoalbuminemia may be associated with Muehrcke lines. The appearance of paired, white bands is most likely due to a chronic nutritional deficiency of albumin. Examples include nephrotic syndrome, glomerulonephritis, liver disease, and malnutrition. Even though the white bands are most often seen in patients with nephrotic syndrome (of which many causes exist), they are not specific for any one disease state.[1] Additionally, Muehrcke lines of the fingernails have been reported after trauma[27] and chemotherapy.[2, 28] Muehrcke lines was also described in a patient with active rheumatoid arthritis.[29] Vitamin A analogues such as trans-retinoic acid and acitretin may also be associated with Muehrcke lines.[30] Of 124 patients with nail changes due to chemotherapeutic agents, four had Muehrcke lines, all four of whom were on a combination of cyclophosphamide/doxorubicin/5-fluorouracil.[31]

See Pathophysiology.

Epidemiology

Frequency

The frequency is unknown.

It was been described in an infant,[32] although most patients with it are much older.

Presentation

History

Muehrcke lines of the fingernails is a transverse leukonychia.[33] They may be evident on both fingernails and toenails.[34] A complete and detailed history is necessary and should include questions concerning occupation and medications. Attention to the chronologic sequence of the events related to the nail abnormality is important. The personal history and a review of systems may also provide important clues to the etiology of the nail changes. Systemic anticancer drug nail changes may cause pain and functional impairment, particularly with taxanes or EGFR inhibitors, but Muehrcke lines are not linked with nail symptoms.[35]

Physical Examination

The two transverse bands originally described by Muehrcke run parallel to the lunule. The bands are separated from each other and from the lunule by areas of normal pink nail, they are not palpable, and they do not indent the nail itself. The distal white band may be wider than the proximal band. The lines are usually found on the second, third, and fourth fingernails; they rarely occur on the thumbnail.[1] The lines are more pronounced with severe and prolonged hypoalbuminemia, and in some patients, they can be reduced or eliminated by intravenous administration of salt-poor serum albumin. They may also be seen following chemotherapy and constitute an aesthetically unpleasant adverse effect of medication and an easily observed sign indicative of previous use of cytotoxic therapy for malignancy.[33]

The physical examination of the nails is valuable in providing clues to the etiology of the nail abnormality. Therefore, a detailed and efficient examination of the nails, in addition to an examination of the rest of the skin and mucous membranes, is essential. Perform a complete physical examination if indicated.

Daniel[8, 36] highlighted a few important points relating to the examination of abnormal nails. If these tests are performed, they provide a more accurate examination. Note the following:

Always examine all 10 fingernails and all 10 toenails (and any additional digits if they exist). For the most part, fingernails provide more subtle information than toenails because trauma is more likely to change or hide certain clinical manifestations in toenails and because they grow more slowly.
Study the nails with the fingers completely relaxed and not pressed against any surface. Failure to do so may affect the nail hemodynamics and change the appearance of the nail.
Blanch the fingertip to see if the pigmented abnormality is grossly altered. This test may aid in differentiating the discoloration of the vascular bed of the nail from the discoloration of the nail plate.
Illumination of the nail can be achieved with a penlight placed against the finger pulp shining up through the nail. If the discoloration is in the matrix or soft tissue, its exact position can be more easily identified. If upon illumination, the discoloration disappears, it is more likely to be in the vascular bed.
Try scraping the surface of the nail plate, or try cleansing locally or cleansing with a solvent (eg, acetone). If in doing so, the discoloration goes away, the cause of the nail alteration is most likely a topical agent. If, however, as a result, the substance used is impregnated further into the nail or subungually, other studies (eg, nail composition studies; potassium hydroxide preparations; biopsy with light microscope, electron microscope, or special staining) may be indicated.
Nail changes associated with systemic disease (as opposed to trauma) often occur in the matrix so that the leading edge of the abnormality (pigmentation) is usually shaped like the distal portion of the matrix. To estimate the time at which the initial insult occurred, one can measure the distance from the proximal nail fold (cuticle) to the leading edge of the pigmentation change. The rate of nail growth is about 0.1-0.15 mm/d.[8]

DDx

Diagnostic Considerations

Also consider the following:

Leukonychia
Beau lines
Mees lines
Erythematous crescent
Terry nails
Half-and-half fingernail
Splinter hemorrhages
Leukonychia associated with increased blood strontium level ^[37]
Melanonychia with onycholysis ^[38]
Onychopapilloma: This benign nail bed neoplasm may be associated with leukonychia. ^[39]
Reflex Sympathetic Dystrophy: This may be associated with changes including unilateral leukonychia, Beau lines, nailfold swelling, nail clubbing, and unilateral atypical trachyonychia. ^[40]

Nails of 100 patients with chronic renal failure under regular hemodialysis were compared with 100 healthy control subjects of matched age and sex.[41] Of these patients, 76% had nail findings, with half and half nails the most common at 20%, followed by—in descending manner—absent lunula, onycholysis, brittle nail, Beau lines, clubbing, longitudinal ridging, onychomycosis, subungual hyperkeratosis, koilonychias, total leukonychia, splinter hemorrhage, pitting, and pincer nail deformity.

Various types of leukonychia may be considered, including leukonychia punctata, leukonychia striata, leukonychia partialis, and leukonychia totalis.[42, 43, 44] “ True” leukonychia involves the nail plate and “apparent” leukonychia derives from the nail bed.[45] Familial leukonychia may rarely be associated with sebaceous cysts, apparently an autosomal dominant genetic disorder.[46] True acquired leukonychia may be associated with trauma, chemotherapeutic agents, hypocalcemia, zinc deficiency, heavy metal poisoning, local infection, and systemic diseases.[47] Selenium deficiency has also been suggested as a possible etiology.[45]

Loss-of-function mutations in calpastatin may produce a syndrome of generalized peeling skin, leukonychia, acral punctate keratoses, cheilitis, and knuckle pads.[48]

Differential Diagnoses

Workup

Laboratory Studies

Obtain appropriate laboratory tests as indicated by the history features and the physical examination findings. The most important test is probably serum albumin measurements. Total serum protein levels, serum chemistry enzyme levels, a urine analysis, and a CBC count are also useful tests. In patients being treated for cancer, obtaining the blood levels of certain chemotherapeutic agents is probably important.

Procedures

Certain studies, including nail composition studies; potassium hydroxide preparations; or biopsy with light microscope, electron microscope, or special staining, may be indicated.

Histologic Findings

According to Nabai, histopathologic sections of the nail plates show compact orthokeratotic keratinous material in combination with areas suggesting some delay in keratinization. No definite evidence of parakeratotic change is present, and no evidence of distortion or thinning of the nail plates exists.[10] James and Odom[26] additionally suggested that the injury may lead to the development of parakeratotic or dyskeratotic foci within the nail matrix and retained in the nail plate; however, they were unable to show such histologic changes in their patient.

Treatment

Medical Care

Treatment should be undertaken in a case-specific manner. In patients presenting with paired, white, transverse lines due to a serum albumin deficiency, albumin infusions to raise the serum level aid in the disappearance of Muehrcke lines. Treatment of the underlying disease additionally aids in correcting the abnormal serum albumin levels.

Muehrcke[1] reported on the effects of intravenous albumin, cortisone, and corticotrophin therapy on the white bands. A 44-year-old engineer with amyloid disease presented with gross proteinuria, white bands on all the fingernails (except the thumb), and a serum albumin level of 1.9 g/100 mL. Over the course of 3 weeks, he was given a total of 750 g of albumin, resulting in a transitory increase in the serum albumin level. After 3 weeks of the albumin infusion, the white bands almost completely disappeared. However, 3 months later, the serum albumin level decreased again, and the bands reappeared.

In a similar fashion, a patient with nephrotic syndrome due to subacute membranous glomerulonephritis received an infusion of 750 g of albumin, which increased his serum level from 2.2 g/100 mL to 3.4 g/100 mL. As a result, the white bands became progressively less visible. Once the serum albumin level returned to the reference range, the white bands fully disappeared.[1]

A third patient with nephrotic syndrome, with a serum albumin level of 1.6 g/100 mL, and with prominent white bands was treated with cortisone therapy over 3 months. At the end of the 3-month period, her serum albumin level increased to 2.9 g/100 mL, and the white bands disappeared.

A 14-year-old boy with anasarca, with a serum albumin level of 1.5 g/100 mL, and with white fingernail bands received 10 days of corticotrophin therapy, followed by a cortisone maintenance treatment. Over the course of several months, his albumin level increased to 3.7 g/100 mL, and the white bands disappeared.[1] Large amounts of multivitamin injections did not have any effect on the appearance of the white bands in the fingernails of patients.[1]

Long-Term Monitoring

Muehrcke lines may be associated with hypoalbuminemia; therefore, patients presenting with the paired, white, transverse bands should be evaluated for certain possible causes. As mentioned earlier, these causes include liver disease, malnutrition, nephrotic syndrome, and glomerulonephritis.

Paired, white, transverse lines are also associated with chemotherapeutic agents. Therefore, other drug options or different treatment regimens should be considered in patients who develop Muehrcke lines while undergoing treatment for cancer.

Author

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, New York Academy of Medicine, Royal College of Physicians of Edinburgh, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Coauthor(s)

Channing R Barnett, MD Staff Physician, Department of Dermatology, University of Medicine and Dentistry of New Jersey

Channing R Barnett, MD is a member of the following medical societies: Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD Former Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Association of Military Dermatologists, Phi Beta Kappa, Texas Dermatological Society

Disclosure: Nothing to disclose.

Warren R Heymann, MD Head, Division of Dermatology, Professor, Department of Internal Medicine, Rutgers New Jersey Medical School

Warren R Heymann, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Richard K Scher, MD Adjunct Professor of Dermatology, University of North Carolina at Chapel Hill School of Medicine; Professor Emeritus of Dermatology, Columbia University College of Physicians and Surgeons

Richard K Scher, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, American Medical Association, Association of Military Surgeons of the US, International Society for Dermatologic Surgery, Noah Worcester Dermatological Society, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

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