Hyperpigmentation throughout the body

Clinical history

A 73 year old Caucasian female presented to a dermatology clinic with physical examination noting brown hyperpigmentation located bilaterally on malar cheeks (Figs 1 and 2). The patient also presented with blue hyperpigmentation on the right and left sclera, the ears, and the left ankle (Fig 1, Fig 2 to 3). The patient reported taking ciclopirox 8% solution, doxepin, fluoxetine, hydroxyzine HCL, levothyroxine, montelukast, restasis, verapamil, and 100 mg of minocycline. The patient reports that the hyperpigmentation started suddenly in the weeks leading up to the appointment and did not worsen over time.

Fig 1.

Fig 2.

Fig 3.

Question 1: What is the best diagnosis?

• A.Addison disease
• B.Melasma
• C.Argyria
• D.Nevus of Ota/Hori
• E.Minocycline-induced hyperpigmentation (MIH)

Answers:

• A.Addison disease – Incorrect. Addison disease can present as hyperpigmentation on sun-exposed areas; however, none of the other symptoms of Addison disease are present. A blood test could be ordered to rule out this condition, but the lack of generalized fatigue, weakness, weight loss, nausea, and mood changes make clinical observation sufficient evidence to rule out Addison disease.
• B.Melasma – Incorrect. Although melasma presents as a brown facial pigmentation, it does not occur in the sclera. This patient presents with a gray pigmentation in the sclera, so melasma is ruled out.
• C.Argyria – Incorrect. Although argyria can present as a gray color in sun-exposed areas including the eyes, the patient had no history of environmental exposure to silver and was not taking any silver-containing medications. Argyria also commonly presents in the mucous membranes, which was absent for this patient.
• D.Nevus of Ota/Hori – Incorrect. While Nevi of Ota/Hori appear as brown or gray lesions on the eyes and face, new nevi do not typically form past the age of 30-40. These lesions are also most common in Asian populations whereas the patient described here is Caucasian.
• E.MIH – Correct. Cutaneous gray or brown pigmentation is a documented effect of chronic minocycline use and is most common in patients taking 100-200 mg daily for over a year. The hyperpigmentation commonly occurs in the skin, nails, teeth, bones, conjunctiva, and sclera. This patient reported taking 100 mg daily by mouth for 11 and a half years and had pigmentation located in the skin and sclera.

Question 2: What is the best treatment?

• A.Pulsed dye laser
• B.Q-Switch/ps laser
• C.Carbon dioxide (CO2) laser
• D.Argon laser
• E.Neodymium-doped yttrium aluminum garnet (Nd:YAG) long pulse

Answers:

• A.Pulsed dye laser – Incorrect. The pulsed dye laser works by mixing an organic dye into a long lasting solvent. A high energy external light source, such as a laser or flashlight, is then used to push the liquid into targeted areas. The wavelength produced by this laser (585-595 nm) is too short, and the pulse duration is too long to effectively target the chromophores in MIP. This laser would be better suited for treating vascular lesions.
• B.Q-Switch/ps laser – Correct. Quality switched or picosecond lasers of varying wavelengths have been demonstrated to provide the best results in terms of clearing minocycline-induced hyperpigmentation.¹ While the exact mechanism is not understood, it is thought that the shorter pulse duration of these lasers allows for photocatalysis to occur in the target chromophores.² There are no current treatments for pigmentation in the sclera.³
• C.CO2 laser – Incorrect. CO2 laser emits light for long durations in a constant beam with high exposure. This light is made up of a combination of 3 gasses: carbon dioxide, helium, and nitrogen. These lasers are used to create thermal damage to the skin to increase collagen production. This would aid in the reduction of scars, not hyperpigmentation.
• D.Argon laser – Incorrect. The argon laser works in a similar way to the CO2 laser, using ionized argon gas to cause selective thermolysis destroying diseased cells. This laser is typically used to treat vascular malformations such as angiomas and telangiectasias, among others. This laser is not used to treat hyperpigmentation.
• E.Nd:YAG long pulse – Incorrect. The Nd:YAG lasers are solid state lasers that emit high energy light to destroy diseased cells. While Q-switched Nd:YAG lasers have been successful in treating MIP, the pulse duration of Nd:YAG long pulse is not short enough to treat MIP. This laser would be more effective in performing laser hair removal.

Question 3: Which of the following is true regarding this diagnosis?

• A.The condition takes years of exposure to the causative agent to occur
• B.Given enough time, the pigmentation will resolve on its own
• C.Patients may present with more than 1 type of this condition simultaneously
• D.Pigmentation of the sclera may be treated by laser
• E.This condition is limited to the skin and sclera

Answers:

• A.The condition takes years of exposure to the causative agent to occur – Incorrect. MIH has been reported to occur in as little as 12 days of minocycline use, particularly in atopic dermatitis patients.⁴
• B.Given enough time, the pigmentation will resolve on its own – Incorrect. Pigmentation affecting the bones and sclera is typically permanent, even after medication cessation. Skin pigmentation may gradually fade, however, complete resolution often requires adjunct treatments.
• C.Patients may present with more than 1 type of this condition simultaneously – Correct. MIH is commonly classified into 4 main types, with the pigmentation affecting different tissues and areas.¹ Type I appears as blue-gray pigmentation at sites of inflammation and scarring. Type II involves blue-gray pigmentation on the legs and forearms. Type III presents as diffuse muddy-brown pigmentation, more pronounced in sun-exposed areas. Type IV involves blue-gray pigmentation within scars. Ocular hyperpigmentation is considered a separate subtype. Our patient exhibits Type I pigmentation at the ankle, Type III pigmentation on the face, and scleral pigmentation.⁵
• D.Pigmentation of the sclera may be treated by laser – Incorrect. While lasers and chemical peels may be effective for skin MIH treatment, there are currently no treatments for scleral pigmentation. Cessation of the medication which may still result in little to no improvement.⁶
• E.This condition is limited to the skin and sclera – Incorrect. MIH can involve various organs and tissues, including nails, teeth, oral mucosa, bone, thyroid gland, conjunctiva, sclera, and skin.

Conflicts of interest

None disclosed.