|Year : 2021 | Volume
| Issue : 2 | Page : 76-85
Nail changes associated with pigmentary disorders
Chander Grover1, Shikha Bansal2
1 Department of Dermatology, Venereology, Leprology, University College of Medical Sciences, New Delhi, India
2 Department of Dermatology and STD, VMMC and Safdarjung Hospital, New Delhi, India
|Date of Submission||31-May-2021|
|Date of Decision||07-Jun-2021|
|Date of Acceptance||28-Jun-2021|
|Date of Web Publication||22-Jul-2021|
Dr. Shikha Bansal
Department of Dermatology and STD, VMMC and Safdarjung Hospital, New Delhi-10029
Source of Support: None, Conflict of Interest: None
Salient nail unit changes serve as pointers toward systemic disease. On similar lines, salient nail changes are associated with pigmentary disorders, and can help toward diagnosis. Nail changes form a part of various physiologic pigmentary changes including racial pigmentation, pregnancy, or neonatal period. At the same time, a number of nail changes can be valuable clues toward disorders of pigmentation associated with genetic syndromes (Laugier–Hunziker syndrome, incontinentia pigmenti, and tuberous sclerosis), endocrine disorders, disorders of metabolism (alkaptonuria), infections (HIV-AIDS), internal malignancies, etc. Nail changes are especially useful if cutaneous pigmentary changes are suspected to be drug-induced based or associated mucosal and/or cutaneous hyperpigmentation. Various drugs that can cause cutaneous pigmentary alterations along with nail changes include cyclophosphamide, adriamycin, vincristine, docetaxel, paclitaxel, carboplatin, psoralens, hydroxyurea, bleomycin, etc. Nail changes are also associated with disorders of hypomelanosis, for example, vitiligo. Pigmentary changes due to endogenous and exogenous pigments are again diagnosable based on the nail changes they induce. This narrative review highlights the importance of nail changes in suspecting and diagnosing various disorders of pigmentation. It also points toward areas which need future research.
Keywords: AIDS, drug induced, endocrine disorders, genetic disorders, malignancy, melanonychia, nail, pigmentary disorders, systemic disorders
|How to cite this article:|
Grover C, Bansal S. Nail changes associated with pigmentary disorders. Pigment Int 2021;8:76-85
| Introduction|| |
Various changes in the nail unit offer reliable indicators of underlying systemic disorders such as splinter hemorrhages in bacterial endocarditis, apparent leukonychia in hypoproteinemia, or chronic liver failure. Similarly, nail unit changes offer clues toward dermatologic diseases including disorders of pigmentation. Nail changes can serve as a valuable aid toward diagnosis of cutaneous pigmentary disorders.
This study is aimed at collating our knowledge regarding manifestations in the nail unit associated with disorders of pigmentation. Familiarity with these nail changes can offer clues toward diagnosis of these disorders, as well as prompt further investigational strategy.
| Methodology|| |
For the purpose of this review, we conducted a PubMed search for articles published in scientific literature in English language regarding the nail changes reported in various disorders of pigmentation. We used the keywords “Pigmentary disorders AND nail,” “systemic disorders,” “endocrine disorders,” “malignancy,” “AIDS,” “drug induced,” “genetic disorders.” These keywords were chosen due to their association or presentation with cutaneous pigmentary changes, and the associated nail manifestations were recorded. The articles were retrieved and classified as case reports, review articles, and clinical trials. Information pertaining to nail changes was recorded. Lesser known disorders were searched individually by name and their nail findings recorded. The collated data were analyzed and were presented in a narrative fashion.
| Physiologic pigmentary alterations and associated nail changes|| |
There are many physiologic cutaneous pigmentary alterations, and in many of these, nail pigmentary changes may occur simultaneously. This category mostly does not require any treatment, neither for the skin color nor for nail changes.
Racial/ethnic pigmentation and nail changes
Darker skin types are associated with a variety of nail unit changes which if not interpreted, in context, can lead to an unnecessary alarm. Racial or ethnic melanonychia is commonly encountered in skin phototypes IV, V, and VI (darkly pigmented races) including Blacks, Asians, Middle-East residents, and Hispanics. It is common for racial melanonychia to involve fingernails (thumb, index finger); arise in multiple nails; and have bands (longitudinal melanonychia) which become broader and extensive with advancing age [Figure 1]. Healthy black individuals may also have a blue lunula at times. Periungual pigmentation is also common in individuals with darker skin color. It may obscure and make it difficult to evaluate changes in nail-fold capillaroscopy. It may occasionally be attributed to friction as well.
|Figure 1 Ethnic pigmentation involving multiple nails in a middle-aged Indian male. Multiple regular, longitudinal pigmented bands of varying width and darkness were observed. The gray to brown color suggests melanocyte activation as a cause.|
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Age-related pigmentary changes and nail manifestations
During infancy, especially the first 6 months of life, there can be a regular reticular pattern of transient light-brown or ochre-colored pigmentation in the periungual area, proximal nail fold (PNF), and dorsal digit extending up to the distal interphalangeal joint. Another condition, the “pseudo-blue-lunulae,” has been reported in a healthy newborn with blue nail color changes, without any sign of cyanosis. This condition spontaneously resolves by 2 weeks of age.
Pregnancy-associated pigmentary and nail changes
Pregnancy is related to hyperpigmentation of skin in many cases. Correspondingly, nail changes may be observed. There is the presence of longitudinal melanonychia that can involve several finger and/or toe nails that may resolve or persist postdelivery. This is generally due to activation of nail matrix melanocytes.
Other than these categories, some nail changes may mislead postmortem evaluation. Nails may appear dark red to blue generally, due to the presence of deoxyhemoglobin attributed to postmortem hypostasis changes. This may not be taken as an indicator of cause of death.
| Disorders of hypermelanosis and their nail manifestations|| |
A large number of disorders of hypermelanosis are associated with nail changes which may in fact appear early, or may even offer a definitive clue toward diagnosis of the pigmentary changes in skin [Table 1].,
|Table 1 Disorders of acquired hyperpigmentation and associated nail changes|
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Lichen planus pigmentosus
Lichen planus pigmentosus (LPP) is a variant of lichen planus characterized by hyperpigmented, slate gray, gray-brown, or blue-brown macules with ill-defined border and mild pruritus of uncertain etiology involving mainly the sun-exposed areas, such as the forehead and temples. Nail lichen planus has been rarely described in association with LPP, even though, it has been reported in about 10% patients of lichen planus. Nail findings associated with lichen planus include onychorrhexis, nail plate thinning, onycholysis, pterygium formation, and red lunulae involving fingernails. Diffuse or longitudinal melanonychia has been reported as a clinical finding in a case of active nail lichen planus, whereas lesions that are healing can give rise to postinflammatory hyperpigmentation leading on to longitudinal melanonychia, more so in darker, pigmented skin type.
Lentiginosis and other genetic syndromes
Lentigines are hyperpigmented macules that do not fade away in the absence of UV exposure. Various syndromes associated with multiple lentigines include Peutz–Jegher syndrome, PTEN (Phosphate and TENsin homolog gene) hamartomatous syndromes, Carney complex lentigines, and LEOPARD syndrome. Some other genetic syndromes are also described.
Laugier–Hunziker syndrome (LHS)
It is characterized by acquired lentigines involving lips, oral mucosa, and acral area, frequently associated with longitudinal melanonychia. Nail pigmentation is reported in LHS in contrast to its absence in Peutz–Jegher syndrome. The incidence of a pigmented nail bands in cases of LHS is 44% to 60%. Longitudinal melanonychia is uncommon in white patients, whereas there is a high incidence of oral or nail pigmentation in Asian population. LHS can be diagnosed only when both oral and nail (or skin) involvement are present.
The nail pigmentation in LHS has been classified by Baran into three main types: a single 1- to 2-mm wide longitudinal streak; double or wider (2–3 mm) longitudinal streaks on lateral parts of nail plate; and homogeneous pigmentation of the radial or ulnar half of the nail. Veraldi et al. added the fourth possibility of complete pigmentation of the nail. All four types of nail involvement may simultaneously involve one or more fingernails and/or toenails, though fingernails are more frequently involved. The degree of pigmentation does not correspond to different stages of the syndrome. Wang et al. described an irregular or stippled pigmentation as a new type of nail pigmentation associated with LHS. Additional features include nail-fold pigmentation termed as pseudo-Hutchinson sign.
Nail pigmentation in LHS needs to be distinguished from pigmentation associated with subungual hemorrhage, candidal onychomycosis, tinea unguium, lichen planus, post-trauma pigmentation, extrinsic staining, chemotherapy, AIDS, malignant melanoma, etc.
It is an autosomal dominant disorder which belongs to category of RASopathies which are developmental syndromes caused by germline mutations (or somatic mosaicism) in genes that alter the RAS subfamily and mitogen-activated protein kinases. It is associated with congenital heart defects, myeloproliferative disorders, chest deformity, cryptorchidism, short stature, and webbed neck. The skin manifestations from early childhood include multiple lentigines, nevi, café-au-lait spots, xerotic skin follicular keratosis, hyperelastic skin, etc. Dystrophic nails can be a finding in a case of Noonan syndrome.
It is a rare noninherited condition characterized by intestinal hamartomatous polyposis, diarrhea, and ectodermal changes. These can be due to malabsorption and malnutrition. The features include lentigines, hyperpigmentation (especially involving limbs, neck, abdomen, trunk, and body folds), hypopigmented macules (involving palms, soles, upper limbs, and chest), and alopecia. Associated nail changes include nail dystrophy (onycholysis, koilonychia) and onychomadesis.
Incontinentia pigmenti (IP)
The IP is a rare neuroectodermal dysplasia due to a defect in the IKBKG gene. The condition is usually lethal in a male fetus; however, females can survive due to X-inactivation mosaicism. Characteristic cutaneous findings follow lines of Blaschko and depend on the stage of development in the first year of life. Additionally, defects of hair, nails, teeth, and systemic involvement are also observed. The central nervous system manifestations involving the eye and brain are responsible for most of the disability. Cutaneous manifestations of IP do not require specific treatment as spontaneous resolution usually occurs.
Nail involvement in IP may be reported in approximately 40% cases. Fingernails are more commonly affected than toenails. Various changes include yellow discoloration, koilonychia, brittle nails, onycholysis, periungual, and subungual tumors. In rare instances or in mild cases, nail changes maybe the sole manifestation of IP. In older patients, periungual and subungual keratotic tumors may be observed, associated with pain, deformities in bone, and lytic lesions in underlying phalanges.
Pigmentary disorders associated with nutritional deficiencies
Pigmentary changes due to malnutrition are usually observed as hyperpigmentary lesions, though hypopigmentation, reticulate, or poikolodermatous changes may also occur less frequently. Many nail changes may be associated with these and are summarized in [Table 2].
|Table 2 Pigmentary changes and nail changes observed in various nutritional deficiencies|
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Vitamin B3 (nicotinic acid) deficiency is associated with pellagra characterized by four “Ds”: diarrhea, dermatitis, dementia, and death. Cutaneous findings present mostly on sun-exposed areas of hands, face, and neck, in the form of edema or vesicle/blister formation followed by desquamation and subsequent hyperpigmentation. Occurrence of half-and-half nails in a case of pellagra has been described.
Vitamin B12 (cyanocobalamin) deficiency is associated with hyperpigmentation, mostly generalized, predominantly observed on sun-exposed areas, flexural regions, and mucosae. Nail pigmentation is often associated, seen as longitudinal melanonychia or diffuse melanonychia. It may even be reversible after supplementation which can also prevent morbidities such as dementia and neuropathy.
Malnutrition, especially protein energy malnutrition and vitamin D deficiency, is often accompanied by melanonychia. Various clinical patterns include longitudinal melanonychia, diffuse bluish and reticulate pigmentation. It can be a result of reduced glutathione levels resulting in disinhibition of tyrosinase leading to excessive melanin. At the same time, leukonychia may also be reported. Terry white nails can be observed in malnourished elderly patients. Pallor of nail bed is a generally observed in anemia. Zinc and calcium deficiency can also lead to transverse leukonychia.
Pigmentary disorders associated with systemic diseases
Various pigmentary changes accompany systemic disorders and hyperpigmentation is an often reported finding. It can be extensive and also dramatically worsen the quality of life of its sufferers. A careful examination of skin and nails in patients with systemic disease, for example, those with end-stage renal disease (ESRD), chronic liver disease, etc., can provide clues toward the systemic disorder being the cause of pigmentary changes, allowing clinicians achieve timely diagnosis and treatment.
The ESRD has frequent concomitant skin involvement which can be extensive and impairs quality of life. Cutaneous features in ESRD include nonspecific and specific manifestations, both of them being difficult to treat dermatoses. Nonspecific manifestations, which are more frequently seen, include pigmentary anomalies, xerosis, half-and-half nails, and pruritus [Figure 2]. Specific associations include acquired perforating dermatosis, bullous dermatoses, metastatic calcification, and nephrogenic systemic fibrosis.
|Figure 2 Half and half nails with longitudinal melanonychia in a patient with end-stage renal disease.|
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Cutaneous pigmentary anomalies associated with ESRD include both pallor and hyperpigmentation, which are often observed along with various nail changes such as absent lunula, nail discoloration, and half-and-half nails.
Chronic liver disease and cirrhosis are associated with a whole spectrum of cutaneous manifestations; the most important being xerosis, excoriated papules, pigmentary changes, jaundice, and pruritus. The nail findings reportedly associated with these include onychomycosis, longitudinal striations, brittle nails, onychorrhexis, clubbing of fingernails, dystrophic nails, leukonychia, and longitudinal melanonychia [Figure 3].
|Figure 3 Brittle nails with discoloration in a patient with chronic liver disease.|
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The HIV-infected patients often have pigmentation involving skin, nails, and mucosae. This has been attributed to various causes including HIV itself, to the extent that pigmentation has been proposed to serve as a cutaneous marker for AIDS. Other pathogenetic mechanisms for pigmentation include adrenocortical insufficiency, nutritional disorders due to folate or vitamin B12 deficiency, drug-induced pigmentation (especially zidovudine), infectious causes (central nervous system toxoplasmosis), neurotropic damage by HIV or an overproduction of interleukin 1 (IL-1) by monocytes.
Nail changes often accompany the pigmentary cutaneous changes. Lahoti et al. reported nail changes to be the most common non-infectious skin manifestation in HIV. Longitudinal melanonychia was the most frequent finding in their study which could be due to Zidovudine, even though it was often seen without antiretrovirals. However, other pigmentary nail changes, including gray and yellow nails, were also reported. Onychomycosis (including proximal subungual onychomycosis, superficial white onychomycosis, and total dystrophic onychomycosis), paronychia, herpetic whitlow, crusted scabies, and Kaposi sarcoma (peri- and subungual lesions) were the other nail changes associated with HIV/AIDS infection.
Addison disease is associated with various oral and systemic manifestations including hyperpigmentation which can be a useful diagnostic sign. Hyperpigmentation is present in 98% of patients with chronic primary adrenal insufficiency, and in many cases, it could be the first clinical manifestation. It can be in the form of diffuse pigmentation, accentuated in flexures. Among the nail changes, longitudinal melanonychia can be the first and only manifestation of Addison disease and is of clinical significance as it can lead to an early diagnosis and prevent life-threatening complications.
Systemic lupus erythematosus (SLE) can be associated with a diffuse facial pigmentation as its predominant manifestation. Postinflammatory pigmentation in the periphery of discoid lesions or even other lesions is also commonly observed. Wagner et al. reported nail changes which can offer valuable clues toward its diagnosis, including longitudinal ridging, periungual erythema, onycholysis, melanonychia, and dyschromia [Figure 4]. However, ungual lesions are not specific enough for diagnosis of SLE.
|Fig 4 Proximal nail-fold erythema with vasculitic lesions in a patient with systemic lupus erythematosus. Ragged cuticle with hangnails can also be seen in this dermoscopic image (10×).|
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Systemic sclerosis is also associated with extensive pigmentary changes including diffuse hyperpigmentation, depigmentation with perifollicular hyperpigmentation (salt and pepper appearance), and a combination of hyper- and hypopigmentation in areas of sclerosis. Associated nail changes include scleronychia, thickened nails, brachyonychia, parrot beaking, trachyonychia, pterygium inversum unguis, splinter hemorrhages, and cuticle abnormalities. Typical nail-fold capillary changes can also prompt toward the diagnosis [Figure 5].
|Figure 5 Nail-fold capillaroscopy showing dilated and tortuous capillaries with avascular area in a patient with systemic sclerosis. Bushy capillaries can also be observed (180×).|
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As discussed above, melanonychia involving multiple finger and toe nails is commonly present with pigmentary disorders, especially those where and underlying systemic disorder is responsible [Table 3]. Such a melnaonychia can be of various patterns including diffuse melanonychia or multiple longitudinal bands. The association with endocrine disorders (Addison disease, Cushing syndrome, hyperthyroidism, and acromegaly); metabolic disorders (hemosiderosis, hyperbilirubinemia, and porphyria), and also AIDS is highlighted above., Additional associations may include internal malignancies (laryngeal carcinoma, lung carcinoma, bronchogenic carcinoma, adenocarcinoma gall bladder and rectum, breast carcinoma) or use of chemotherapeutic agents. Melanonychia and erythronychia can be a finding in graft versus host disease as well (GVHD).
Drug-induced pigmentary changes
Several drugs cause cutaneous pigmentation including cytotoxic agents, analgesics, anticoagulants, antimicrobials, antiretrovirals, metals, and antiarrhythmic drugs. The mechanisms of such drug-induced cutaneous pigmentary changes are diverse. Associated nail anomalies can be present in few, multiple, or all 20 nails.
Generally, diagnosis of drug-associated pigmentation is based on a temporal correlation with administration of the drug. It may also present with mucosal and cutaneous hyperpigmentation. During its natural course, pigmentation may fade partially or completely following drug withdrawal over 6 to 8 weeks. However, longer lasting changes over several months to years are known. These pigmentary changes may be melanic or nonmelanic. However, in the nail-associated changes are mostly due to melanin produced by a toxic effect on nail matrix melanocytes. Melanonychia presenting as a single longitudinal band is presumably due to activation of a cluster of melanocytes, whereas melanonychia involving entire nail plate could be due to diffuse activation. Various drugs incriminated for diffuse melanonychia include cyclophosphamide, adriamycin, vincristine, docetaxel, paclitaxel, carboplatin, psoralens, hydroxyurea, bleomycin, etc.; whereas drugs such as zidovudine, psoralens, and radiation therapy induce longitudinal or diffuse melanonychia. Transverse melanonychia is another pattern commonly observed in this setting. It runs parallel to lunula, alternating with bands of normal color, usually due to intermittent administration of chemotherapy. Drug-related melanonychia typically fades slowly following drug withdrawal. Zidovudine-induced nail pigmentation is common, especially in dark-skinned individuals. It can be due to increased melanin pigment and melanosomes in the epidermis and appears around 4 to 8 weeks after initiation of treatment (can appear as late as 6 months). Though it is cosmetically unpleasant, substitution of drug is generally not advisable.
At times, nonmelanic cutaneous and nail pigmentation may also occur. It is due to excretion of drug via nail matrix, which then gets integrated into the nail plate and is eliminated with its growth. This category includes yellow discoloration due to tetracyclines and dark-brown pigmentation due to clofazimine. Imatinib can lead to blue-gray pigmentation of nails apart from pigmentary anomalies involving skin, palatal mucosa, teeth, hair, and gums. Though hypopigmentation due to inhibition of melanogenesis is a common side effect with imatinib; hyperpigmentation has also been rarely reported, in the form of melasma-like facial pigmentation. Minocycline-induced blue-gray pigmentation spares the lunula, whereas pigmentation of skin, sclerae, and mucous membranes is noted possibly due to dermal deposition of iron chelates of the drug.
Deposition of various pigments (drug, hemosiderin, or melanin) in the dermis often leads to pigmentation of skin and mucosae. In these cases, nail discoloration involves the subungual area. Such a pigmentation does not move with nail growth. Antimalarials cause such blue, brown, or gray discoloration in nails which does not move distally. It is associated with skin, nail, and eye pigmentation. A decrease in intensity may be noticed upon discontinuation of offending drug; however, complete resolution is unlikely.
| Disorders of hypomelanosis and their nail manifestations|| |
Disorders of hypomelanosis include both depigmented and hypopigmented conditions. Nail changes have been described in association with some of these as well. Salient nail changes associated with disorders of hypomelanosis are detailed below.
Genetic and nevoid disorders
Tuberous sclerosis complex (TSC) is a genetic multisystem disorder with prominent skin features, many of which are identifiable in childhood. Among the dermatologic manifestations, the most common and earliest onset are hypomelanotic macules (ash leaf spots), facial angiofibromas, shagreen patches, etc. Distinctive nail changes include longitudinal leukonychia, being reported in 18% of cases of tuberous sclerosis. Multiple ungual fibromas are one of the major criteria for the diagnosis of TSC [Figure 6]. These present as firm, smooth, skin-colored, or erythematous papules around fingernails and toenails around puberty, in 20% of patients. Mostly they are asymptomatic, however, in few cases, they can cause nail deformity and pain.
|Figure 6 Koenen tumors with melanonychia in a patient with tuberous sclerosis.|
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Nail changes have been associated with vitiligo; hence, it is recommended to do a systematic examination of the nails in these patients. Vitiligo is associated with other autoimmune diseases including alopecia areata, which themselves have frequently accompanying nail changes. In a study conducted by Topal et al., longitudinal ridging and leukonychia were the most common associated abnormalities in patients with vitiligo. Other nail findings include absent lunula, onycholysis, nail-bed pallor, onychomycosis, splinter hemorrhages, and nail plate thinning. Twenty nail dystrophy (revised terminology: trachyonychia) has been found to be rarely associated with vitiligo. It may be due to common autoimmune injury to the melanocytes and the nail matrix. The “nail flag sign” has been reported in 6% vitiligo patients by Anbar et al. These patients present with alternating white and pink-red horizontal bands beginning at the PNF and extending distally to the free edge of the nail plate. Apart from vitiligo, it has been noted in individuals with diabetes mellitus, diverticulitis, and leprosy.
| Endogenous pigments and their nail manifestations|| |
It is a hereditary disorder in which iron salts are deposited in the tissues, leading to liver damage, diabetes mellitus, and bronze discoloration of the skin. It occurs in both primary and secondary forms. The cutaneous pigmentation could be metallic-gray, slate-gray, or brownish-bronze, involving sun-exposed areas, and mainly seen as an early sign of the disease. Apart from similar deposits being reported in nails, koilonychia has also been reported as an additional nail manifestation of hemochromatosis.
It is a rare autosomal recessive disorder of tyrosine metabolism caused by deficiency of homogentisate 1,2-dioxygenase enzyme. Homogentisic acid is oxidized to benzoquinone acetate, which polymerizes to form a melanin-like dark yellow pigment or “ochre,” which is deposited in the cartilage and other connective tissue, producing the characteristic manifestation − ochronosis. This deposition is associated with a debilitating morbidity. These patients may also present with uniform bluish discoloration of nails along with pigmentation of other body parts including the sclera (Osler sign), ear cartilage, tragus, mucosae, tendons, crown of teeth, thenar and hypothenar eminences, and sides of fingers. Dermoscopy shows bluish longitudinal streaks suggesting pigment deposition within vessel walls.
Other endogenous pigments
Bilirubin and carotenoids are the yellow chromophores, with minor contributions to normal skin color. However, in cases with an increase in the concentration of these, a yellowish hue is imparted to both the skin and nails.
| Exogenous pigments and their nail manifestations|| |
Skin and nail pigmentation can be a result of contact with exogenous substances that include dyes, animal toxins, food, tobacco, etc. Tobacco smoke can lead to skin pigmentation with a smoker’s facial skin having increased melanin, whereas oral mucosal pigmentation is caused by increased melanin production due to heat generated by smoking. A brown to black pigmentation of nails may be seen in these patients, consequent to exogenous agents including dirt, tobacco, potassium permanganate, and tar. This pigmentation may be confined to the nail plate or can extend to involve nail folds and periungual region as well; however, proximal nail plate and lunula are generally spared.
Argyria is an uncommon condition caused by ingestion of silver compounds which leads to silver salt deposits in skin, nails, and mucous membranes. There is a permanent blue or blue-gray uniform pigmentation, involving face and various sun-exposed areas. In the nails, silver nitrate deposition presents as a dark color band with an irregular medial border and staining of adjacent skin of nail folds. Medical treatment is not effective. Gold particles can also be similarly deposited in nail plates causing yellow nail discoloration in rheumatoid arthritis patients treated with gold salts.
| Conclusion|| |
Disorders of pigmentation can be both due to excess or decreased (even absent) pigment. Melanin is the most important chromophore but various nonmelanin contributors, both exogenous and endogenous, are responsible for producing a spectrum of cutaneous pigmentary disorders. Nail manifestations, though not very frequently associated with disorders of pigmentation, can offer valuable clues toward suspecting or diagnosing these disorders, both hypopigmentary and hyperpigmentary.
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| References|| |
Lawry M, Daniel CR 3rd. Nails in systemic disease. In: Scher RK, Daniel CR, eds. Nails: Diagnosis, Therapy, Surgery. 3rd ed. Philadelphia: Elsevier Science Limited; 2005. p. 147‑69.
Dika E, Starace M, Lambertini M et al.
Oral and nail pigmentations: a useful parallelism for the clinician. J Dtsch Dermatol Ges 2020;18:7-14.
DeNicola P, Moriani M, Zavagli G. Anatomy and Physiology. Nail Diseases in Internal Medicine. Springfield: Charles C. Thomas 1974. p. 1–5
Jakhar D, Grover C, Singal A, Das GK. Nailfold capillaroscopy and retinal findings in patients with systemic sclerosis: is there an association? Indian Dermatol Online J 2020;11:382-6. [Full text]
Starace M, Alessandrini A, Piraccini BM. Nail disorders in children. Skin Appendage Disord 2018;4:217-29.
Siddiqui Y, Rashid RM. Pseudo-blue lunula and beyond: a normal variant. Skinmed 2010;8:363-4.
Monteagudo B, Suárez O, Rodriguez I et al.
Longitudinal melanonychia in pregnancy. Actas Dermosifiliogr 2005;96:550.
Langlois NE. Digital image analysis of fingernail colour in cadavers comparing carbon monoxide poisoning to controls. Forensic Sci Med Pathol 2010;6:9-12.
Baran R. Longitudinal melanotic streaks as a clue to Laugier-Hunziker syndrome. Arch Dermatol 1979;115:1448-9.
Veraldi S, Cavicchini S, Benelli C, Gasparini G. Laugier-Hunziker syndrome: a clinical, histopathologic, and ultrastructural study of four cases and review of the literature. J Am Acad Dermatol 1991;25:632-6.
Mendiratta V, Jain A. Nail dyschromias. Indian J Dermatol Venereol Leprol 2011;77:652-8.
] [Full text]
Elmansour I, Chiheb S, Benchikhi H. Nail changes in connective tissue diseases: a study of 39 cases. Pan Afr Med J 2014;18:150.
Lemes LR, Verde RB, Durães SM, Araripe AA Junior, Pantaleão L. Coexistence of nail lichen planus and lichen planus pigmentosus. An Bras Dermatol 2016;91(Suppl 1):20-2.
Żychowska M, Żychowska M. Nail changes in lichen planus: a single-center study. J Cutan Med Surg 2021:25:281-5.
Baran R, Jancovici E, Sayag J, Dawber RP. Longitudinal melanonychia in lichen planus. Br J Dermatol 1985;113:369-70.
Yago K, Tanaka Y, Asanami S. Laugier-Hunziker-Baran syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;106:e20-5.
Wang WM, Wang X, Duan N, Jiang HL, Huang XF. Laugier-Hunziker syndrome: a report of three cases and literature review. Int J Oral Sci 2012;4:226-30.
Van den Berg H, Schreuder WH, Jongmans M et al.
Multiple giant cell lesions in a patient with Noonan syndrome with multiple lentigines. Eur J Med Genet 2016;59:425-8.
Sweetser S, Boardman LA. Cronkhite-Canada syndrome: an acquired condition of gastrointestinal polyposis and dermatologic abnormalities. Gastroenterol Hepatol (NY) 2012;8:201-3.
Greene-Roethke C. Incontinentia Pigmenti: a summary review of this rare ectodermal dysplasia with neurologic manifestations, including treatment protocols. J Pediatr Health Care 2017;31:e45-52.
Poziomczyk CS, Recuero JK, Bringhenti L et al.
Incontinentia pigmenti. An Bras Dermatol 2014;89:26-36.
Ma Y, Xiang Z, Lin L, Zhang J, Wang H. Half-and-half nail in a case of isoniazid-induced pellagra. Postepy Dermatol Alergol 2014;31:329-31.
Seshadri D, De D. Nails in nutritional deficiencies. Indian J Dermatol Venereol Leprol 2012;78:237‐41. [Full text]
Galperin TA, Cronin AJ, Leslie KS. Cutaneous manifestations of ESRD. Clin J Am Soc Nephrol 2014;9:201-18.
Rashpa RS, Mahajan VK, Kumar P et al.
Mucocutaneous manifestations in patients with chronic kidney disease: a cross-sectional study. Indian Dermatol Online J 2018;9:20-6.
] [Full text]
Salem A, Gamil H, Hamed M, Galal S. Nail changes in patients with liver disease. J Eur Acad Dermatol Venereol 2010;24:649-54.
Grover C, Kubba S, Bansal S, Nanda S, Reddy BS. Pigmentation: a potential cutaneous marker for AIDS? J Dermatol 2004;31:756-60.
Lahoti S, Rao K, Umadevi HS, Mishra L. Correlation of mucocutaneous manifestations of HIV-infected patients in an ART center with CD4 counts. Indian J Dent Res 2017;28:549-54.
] [Full text]
Prat C, Viñas M, Marcoval J, Jucglà A. Longitudinal melanonychia as the first sign of Addison’s disease. J Am Acad Dermatol 2008;58:522-4.
Calleja Algarra A, Aragón Miguel R, Prieto Barrios M et al.
Generalized facial pigmentation: an uncommon presentation of cutaneous lupus erythematosus. Indian J Dermatol Venereol Leprol 2020;86:431-5.
Wagner C, Chasset F, Fabacher T, Lipsker D. Lupus érythémateux et atteinte unguéale: revue de la littérature [Ungual lesions in lupus erythematosus: a literature review]. Ann Dermatol Venereol 2020;147:18-28 [in French].
Marie I, Gremain V, Nassermadji K et al.
Nail involvement in systemic sclerosis. J Am Acad Dermatol 2017;76:1115-23.
Singal A, Bisherwal K. Melanonychia: etiology, diagnosis, and treatment. Indian Dermatol Online J 2020;11:1-11
Lateur N, Andre J. Melanonychia: diagnosis and treatment. Dermatol Ther 2002;15:131-41.
Baran R, Dawber RPR, Richert B. Physical signs. In: Baran R, Dawber RPR, deberker DAR, Haneke E, Tosti A eds. Baran and Dawber’s Diseases of the Nails and their Management. 3rd ed. Oxford: Blackwell Science 2001. p. 85-96.
Chang C, Beutler BD, Cohen PR. Polydactylous transverse erythronychia: report of a patient with multiple horizontal red bands affecting the fingernails. Dermatol Ther (Heidelb) 2017;7:255-62.
Piraccini BM, Tosti A. Drug-induced nail disorders. Drug Saf 1999;21:187-201.
Saraswat N, Sood A, Verma R, Kumar D, Kumar S. Nail changes induced by chemotherapeutic agents. Indian J Dermatol 2020;65:193-8. [Full text]
Di Tullio F, Mandel VD, Scotti R, Padalino C, Pellacani G. Imatinib-induced diffuse hyperpigmentation of the oral mucosa, the skin, and the nails in a patient affected by chronic myeloid leukemia: report of a case and review of the literature. Int J Dermatol 2018;57:784-90.
Subhadarshani S, Abhishek GN. Imatinib-induced melasma-like pigmentation. Indian J Dermatol 2019;64:158-9.
] [Full text]
Aldrich CS, Hong CH, Groves L, Olsen C, Moss J, Darling TN. Acral lesions in tuberous sclerosis complex: insights into pathogenesis. J Am Acad Dermatol 2010;63:244-51.
Northrup H, Krueger DA, International Tuberous Sclerosis Complex Consensus Group. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol 2013;49:243-54.
Topal IO, Gungor S, Kocaturk OE, Duman H, Durmuscan M. Nail abnormalities in patients with vitiligo. An Bras Dermatol 2016;91:442-5.
Khandpur S, Bansal A, Sharma VK, Bhatti SS, Singh MK. Twenty nail dystrophy in vitiligo. J Dermatol 2007;34:189-92.
Anbar T, Hay RA, Abdel-Rahman AT, Moftah NH, Al-Khayyat MA. Clinical study of nail changes in vitiligo. J Cosmet Dermatol 2013;12:67-72.
Cohen PR. The nail flag sign: case report in a man with diverticulitis and review of dermatology flag sign of the hair, skin, and nails. Cureus 2018;10:e2929.
Abdel-Naser MB. The colour of skin: gray diseases of the skin, nails, and mucosa. Clin Dermatol 2019;37:507-15.
Zatkova A. An update on molecular genetics of alkaptonuria (AKU). J Inherit Metab Dis 2011;34:1127-36.
Sirka CS, Rout AN, Naik S, Sahu K. Blue palms and nails: a clue to diagnosis of alkaptonuria. Indian J Dermatol Venereol Leprol 2020;86:753.
Logan IT, Logan RA. The color of skin: yellow diseases of the skin, nails, and mucosa. Clin Dermatol 2019;37:580-90.
Molina-Hernandez AI, Diaz-Gonzalez JM, Saeb-Lima M et al.
Argyria after silver nitrate intake: case report and brief review of literature. Indian J Dermatol 2015;60:520.
] [Full text]
Fam AG, Paton TW. Nail pigmentation after parenteral gold therapy for rheumatoid arthritis: ‘gold nails’. Arthritis Rheum 1984;27:119-20.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2], [Table 3]