PHYSICAL FINDINGS

Thomas J. Marrie, MD, Section Editor

Pseudocyanosis: Drug-Induced Skin Hyperpigmentation Can Mimic Cyanosis

Jason Weatherald, BSc,a Thomas J. Marrie, MDb
a

Department of Medicine, University of Alberta, Edmonton; bFaculty of Medicine and Dentistry, Walter C. Mackenzie Health Sciences Center, University of Alberta, Edmonton, Alberta, Canada.

Cyanosis is an important manifestation of cardiovascular or pulmonary dysfunction that is dened as a blue or grayish discoloration of the skin or mucous membranes. It is caused by an increased amount of reduced hemoglobin circulating in the blood.1 While there are many different causes of both central and peripheral cyanosis,2 it is important for the clinician to be aware that several drugs and heavy metals can result in a bluish or slate-gray pigmentation of the skin that can be confused with cyanosis. This drug-induced skin discoloration is sometimes referred to as pseudocyanosis, as it must be distinguished from true cyanosis.1 This article will briey review some of the most commonly implicated drugs causing pseudocyanotic skin pigmentation.

fore the advent of newer atypical antipsychotic drugs.3 Among the many reported side effects of prolonged high-dose administration of chlorpromazine is a diffuse violaceous or purplish grey discoloration of sun-exposed areas of the face, neck, and the dorsum of the hands that occurs almost exclusively in women,4 but can occur in men, as illustrated by our patient. Deposition of golden-brown pigment granules around capillaries in the dermis have been shown to be responsible for chlorpromazine-induced hyperpigmentation.4

Amiodarone
Amiodarone is an antiarrhythmic and a coronary vasodilator that commonly causes photosensitivity and can, in some instances, cause a slate gray or purplish pigmentation of the face.5 This discoloration appears on sun-exposed surfaces and may be confused with cyanosis when occurring on the hands, or around the mouth or lips.

CLINICAL SCENARIO
The patient, a 70-year-old white man was admitted to the neurosurgery service for investigation of headaches. The admitting physician noted bluish discoloration of the skin of his face and hands (Figure) and made a diagnosis of cyanosis. The examination of the heart and lungs was normal. The lips were not cyanotic. It also was noted that only sun-exposed areas of skin had a bluish discoloration. Oxygen saturation as determined by pulse oximetry was normal. Further history revealed that the patient had been treated with chlorpromazine daily for the past 20 years. At this point, a diagnosis of chloropromazine-induced skin discoloration was made.

Minocycline
This commonly used antibiotic of the tetracycline family is a well-documented cause of skin discoloration in several distributions, including a pseudocyanotic blue-black pigmentation of the shins, ankles, and arms (Type II distribution). It also can cause a bluish discoloration of the oral cavity, particularly of the bones underlying the oral mucosa. In some rarer cases, the oral mucosa itself may discolor, making it even more difcult to discern between pseudocyanosis and true cyanosis.6 Because of the widespread use of minocycline, it is important to be aware of this side effect and include a thorough drug history so as not to confuse this pigmentation with cyanotic changes.

DRUGS THAT CAN CAUSE SKIN PIGMENTATION RESEMBLING CYANOSIS

Chlorpromazine
Chlorpromazine was the rst and one of the most widely used conventional antipsychotic drug for treating schizophrenia beRequests for reprints should be addressed to Thomas J. Marrie, MD, Faculty of Medicine and Dentistry, 2J2.01 Walter C. Mackenzie Health Sciences Center, 8440 112 Street, Edmonton, AB T6G 2R7, Canada. E-mail address: tom.marrie@ualberta.ca

HEAVY METALS THAT CAN CAUSE PSEUDOCYANOSIS

Silver (Argyria)
Historically, silver salts were used in the treatment of epilepsy but now are used only for local cutaneous or ocular treatment,

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The American Journal of Medicine, Vol 121, No 5, May 2008 deposited permanently in the dermis of light-exposed skin and, with increasing cumulative dose, may eventually lead to blue or slate-gray pigmentation of the face and neck. Chrysiasis is common and under-recognized in patients receiving gold treatment and, although benign, may be misdiagnosed as cyanosis.11

APPROACH TO PSEUDOCYANOSIS
When cyanosis is suspected, the gold standard for evaluation is arterial blood gas measurement with co-oximetry. The presence of normal PaO2 and normal hemoglobin concentrations suggests abnormal hemoglobin or abnormal skin pigmentation, as in pseudocyanosis. Clinically, pseudocyanosis also can be distinguished from cyanosis as it does not blanch with pressure, whereas cyanotic skin does.1

References
1. Stapczynski JS. Respiratory diseases: Cyanosis. In: Tintinalli JE, Kelen GD, Stapczynski JS, eds. Emergency Medicine: A Comprehensive Study Guide, 6th edn. New York, NY: McGraw-Hill, Medical Publishing Division; 2004:443-444. 2. Kasper DL, Braunwald E, Hauser S, et al. Harrisons Principles of Internal Medicine, 16th edn. New York, NY: McGraw-Hill, Medical Publication Division; 2005. 3. Bhatara VS, Lpez-Muoz F, Gupta S. Guest editorial: celebrating the 50th anniversary of the introduction of chlorpromazine in North America and the advent of the psychopharmacology revolution. Ann Clin Psychiatry. 2005;17:109-111. 4. Greiner AC, Berry K. Skin pigmentation and corneal and lens opacities with prolonged chlorpromazine therapy. Can Med Assoc J. 1964;90: 663-665. 5. Harris L, McKenna WJ, Rowland E, et al. Side effects of long-term amiodarone therapy. Circulation. 1983;67:45-51. 6. Eisen D, Hakim MD. Minocycline-induced pigmentation. Incidence, prevention and management. Drug Saf. 1998;18:431-440. 7. Levantine A, Almeyda J. Drug induced changes in pigmentation. Br J Dermatol. 1973;89:105-112. 8. Hendrix JD Jr, Greer KE. Cutaneous hyperpigmentation caused by systemic drugs. Int J Dermatol. 1992;31:458-466. 9. Chang AL, Khosravi V, Egbert B. A case of argyria after colloidal silver ingestion. J Cutan Pathol. 2006;33:809-811. 10. Dereure O. Drug-induced skin pigmentation. Epidemiology, diagnosis and treatment. Am J Clin Dermatol. 2001;2:253-262. 11. Smith RW, Leppard B, Barnett NL, et al. Chrysiasis revisited: a clinical and pathological study. Br J Dermatol. 1995;133:671-678.

Figure The patient shows signs of chlorpromazine-induced pseudocyanosis.

although application to mucous membranes may result in sufcient absorption to cause side effects such as argyria.7 This hyperpigmentation caused by systemic silver ingestion is usually blue to slate-gray, occurring in sun-exposed areas and occasionally in the sclera, nails, and mucous membranes.8 Despite the decrease in the use of silver in medications, a recent article noted that the use of colloidal silver in some alternative health products may lead to a cyanotic blue-gray appearance of the cheeks and nose.9

Gold (Chrysiasis)
Gold salts are used as treatment in several common conditions such as rheumatoid or psoriatic arthritis.10 Gold is