Gray-blue discoloration of the proximal nail beds

Case presentation

A 58-year-old Caucasian woman presented with asymptomatic gray-blue discoloration of the proximal nail beds of her fingernails (Fig 1). She described 5 years of gradually worsening gray-blue perioral macules coalescing into patches and on examination was observed to also have diffuse gray-blue discoloration of the bilateral auricular helices and sclerae. Her past medical history was significant for smoking, nephrolithiasis, acne vulgaris and hidradenitis suppurativa. The patient declined biopsy or treatment.

Fig 1.

Question 1: What is the most likely diagnosis?

• A.Normal variant
• B.Argyria
• C.Minocycline-induced pigmentation
• D.Wilson disease (hepatolenticular degeneration)
• E.B12 deficiency

Answers:

• A.Normal variant – Incorrect. Although blue lunula can be observed in otherwise healthy black individuals,¹ it would not be considered normal variant in a patient of this skin type. The gray-blue discoloration also extends into the nail bed, beyond the lunula, in this case.
• B.Argyria – Incorrect. Argyria is in the differential diagnosis for blue lunula. This patient did not have a history of silver supplementation or other exposure.
• C.Minocycline-induced pigmentation – Correct. Given the patient’s past medical history of acne and hidradenitis suppurativa, for which tetracycline antibiotics are frequently utilized, and blue-gray pigmentation of her skin, sclera(Fig 2), helices (Fig 3), and nail beds, this is the correct diagnosis. She took minocycline 100 mg daily by mouth for 25 years.
• D.Wilson disease (hepatolenticular degeneration) – Incorrect. Wilson disease, an autosomal recessive disorder of copper metabolism, is in the differential for a patient with blue lunula; however, the color does not extend into the nail bed as in this case. Wilson disease also presents with cirrhosis, hyperpigmentation, and pruritus.¹
• E.B12 deficiency – Incorrect. Blue or blue-black discoloration of the nails can be observed in the setting of vitamin B12 deficiency,² however this is diffuse and secondary to melanocyte activation as opposed to depositional etiology as in this case.

Fig 2.

Fig 3.

Question 2: What type(s) of minocycline hyperpigmentation is known to increase in incidence with higher cumulative dose?

• A.Type I: blue-black macules in areas of acne scarring or inflammation on the face
• B.Type II: blue-gray macules or diffuse discoloration at sites distant from inflammation
• C.Type III: diffuse muddy-brown discoloration on sun-exposed skin
• D.Type IV: blue-gray macules in areas of scarring on the back
• E.Types II and III

Answers:

• A.Type I: blue-black macules in areas of acne scarring or inflammation on the face – Incorrect. Type I does not appear to be related to cumulative dose or duration.³ This typically resolves several months after minocycline is discontinued.
• B.Type II: blue-gray macules or diffuse discoloration at sites distant from inflammation – Incorrect. Although true, this is not the best answer. This patient best classifies as Type II, given involvement of the nails, sclera, and cartilage. This typically resolves months after minocycline is discontinued.³
• C.Type III: diffuse muddy-brown discoloration on sun-exposed skin – Incorrect. Although true, this is not the best answer. In contrast to types I and II, this pigmentary change persists indefinitely.³
• D.Type IV: blue-gray macules in areas of scarring on the back – Incorrect. In this more recently reported entity, the patients were on shorter courses of minocycline with low cumulative dose, similar to Type I.³
• E.Types II and III – Correct. Both Types II and III are associated with prolonged or high dose minocycline intake, with previous reports noting between 70 to 100 g of cumulative dose as a risk factor.^3,4

Question 3: Which of the following is most likely to be the initial location of minocycline pigmentation?

• A.Nails
• B.Mandible
• C.Cartilage
• D.Axillae
• E.Sclera

Answers:

• A.Nails – Correct. Minocycline pigmentation usually occurs after prolonged treatment; however, it is not always dose dependent. There are reports of nail pigmentation presenting as early as 8 weeks into a minocycline course,⁵ therefore it has been suggested that nail bed discoloration may be the first location of pigmentation.
• B.Mandible – Incorrect. There are reports that 10% of patients taking minocycline between 100 and 200 mg/day for greater than 1 year had intraoral bone pigmentation and 20% had this finding after taking minocycline for 4 years.⁴ Blue or blue-black discoloration of the bone can be seen through the semi-translucent maxillary and mandibular anterior alveolar mucosa.
• C.Cartilage – Incorrect. Cartilage pigmentation has been reported in patients taking minocycline for over 1 year.⁴
• D.Axillae – Incorrect. Type I minocycline pigmentation involves the face, Type III minocycline pigmentation involves sun-exposed skin, and Type IV minocycline pigmentation involves the back. Intertriginous areas are typically uninvolved.
• E.Sclera – Incorrect. Scleral pigmentation is seen in patients taking minocycline for years. Of note, it has been observed that almost all patients with scleral pigmentation also have pigmentation of the nails.⁴

Conflicts of interest

None disclosed.