The father of a healthy 15-year-old girl brings her to the emergency department (ED) for evaluation of blue hands.
The father of a healthy 15-year-old girl brings her to the emergency department (ED) for evaluation of blue hands.
Her father reported to the ED staff that his daughter had called him in the middle of a meeting right after she had given a stressful oral presentation. She said that her hands were blue and she couldn’t breathe. The father instructed his daughter to go directly to the nurse’s office to seek help. When he arrived at her school to pick her up, he found his daughter tearful, but not out of breath. Her lips were pink but her hands were dusky and blue. That’s when he rushed her to the pediatric ED.
In the ED, the girl was immediately connected to a pulse oximeter that showed oxygen saturation levels of 99%. She was alert and oriented, but tearful when she looked at her hands again. She was afebrile; blood pressure was 105/68 mm Hg. Her physical exam showed moist mucous membranes and no perioral cyanosis. She had no murmurs and her lung exam was normal without wheezing, tachypnea, or increased work of breathing. Her abdominal exam was normal with no organomegaly.
The rest of her exam, including a neuromuscular exam, also was normal with the exception of her hands that had a dusky-blue color especially concentrated on the dorsum of her hands (Figure). The astute ED resident asked if she had touched anything blue that day or if she was wearing any new clothing that was blue. Her answer was neither. She recounted that the only thing that was different about this day was that she had been nervous about her oral presentation just prior to her hands turning blue and her trouble breathing.
Her laboratory tests were completely normal and included a complete blood count with normal differential; a normal comprehensive metabolic panel; a negative antinuclear antibody test (ANA; <1:40); a normal erythrocyte sedimentation rate (ESR) of 14; normal thyroid stimulating hormone (TSH) and free thyroxin (free T4); and normal urinalysis.
An electrocardiogram (EKG) was done and demonstrated a normal sinus rhythm with no abnormalities.
The ED physician looked over the labs, and then looked at her blue hands and shook his head. The discharge diagnosis was acrocyanosis, but she would have to follow up with both Cardiology and Rheumatology for a more definitive cause.
Color changes in the distal extremities can occur as a result of constriction or dilatation of blood vessels, as seen in Raynaud phenomenon (RP) and in acrocyanosis; tissue ischemia secondary to arterial occlusion attributed to blood clots, emboli or vasculitis; or as a result of hypoxemia or methemoglobinemia (Table 1).
“Classic” RP includes paroxysmal, reversible, triphasic color change in the fingers and toes, including pallor (white), cyanosis (blue) and hyperemia (red). It may be primary in the absence of accompanying disease, or secondary to an underlying connective tissue disease, in particular scleroderma or lupus.1 The color changes in RP typically are triggered by cold and stress, but can also occur spontaneously. They usually involve a few digits at a time, often asymmetric, extending only to a distal portion of the digit, sparing the hands and thumbs, and with a clear line of demarcation. Reynaud phenomenon also may involve all the fingers, toes, ears, and the nose.
Some patients note only the blue phase of the color changes, making the distinction from acrocyanosis difficult. Reynaud phenomenon is attributed mainly to hyperactivity of the sympathetic nervous system causing episodic vasospasm in the peripheral small vessels. This patient had no family history or personal history of RP.
Acrocyanosis is a relatively common finding that has some resemblance to RP, as the color changes are also transient and seem to be triggered by cold and stress. However, in acrocyanosis the color changes are more symmetric; extend to the hands and even the forearms; there is no clear line of demarcation; the thumbs are often involved; and the episodes are usually longer than RP episodes.2 Acrocyanosis is caused by vasoconstriction of small arteries and arterioles, and hypotonic dysregulation of small venules, resulting in blood stasis and deoxygenation. Acrocyanosis can be primary, without an underlying disease, or secondary to neoplastic (paraneoplastic disorder), neurologic (neuropathies), and other disorders (cryoglobulinemia, eating disorders).3
To note, psychostimulant drugs used to treat attention deficit/hyperactivity disorder (ADHD) have been associated with triggering and worsening the symptoms of both RP and acrocyanosis.4
Erythromelalgia is a condition characterized by paroxysmal erythema, warmth, and extreme pain of the distal extremities. It is typically symmetric. Episodes are triggered by exposure to warmth and relieved by cooling. Erythromelalgia may be primary and has been associated with several missense mutations in SCN9A, a gene encoding a sodium channel.5 It may be secondary to polycythemia, thrombocytosis, vascular disease, and peripheral neuropathy.
Other entities that may cause color changes in the distal extremities include venous and arterial occlusions as a result of blood clots or emboli. These are typically fixed rather than transient color changes and are associated with significant pain from tissue ischemia and necrosis.
Vascular occlusion also might be a result of vasculitis associated with blood vessel damage leading to poor perfusion and color changes in the distal extremities. Primary vasculitides, in particular those affecting small vessels such as granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA; formerly Churg-Strauss syndrome), need to be considered.
Hypoxemia also might present with color changes in the distal extremities, but similar discoloration usually is also noted in the lips, tongue, and perioral region. It may be a result of hypoventilation and cardiorespiratory pathologies.
Methemoglobinemia may also present with distal and central cyanosis secondary to an increase in the level of methemoglobin in the blood usually as a result of exposure to various medications and chemicals. The increased methemoglobin causes blue discoloration and at times tissue hypoxemia because of increased affinity of the hemoglobin to oxygen and decreased release of oxygen to the tissues.
Finally, discoloration of the skin of the distal extremities as a result of colored sweat or interaction of colorless sweat with an agent present on the skin can lead to unusual color as well. These conditions are referred to as chromhidrosis or pseudochromhidrosis (Table 2).6
Pseudochromhidrosis is a rare condition wherein sweat interacts with various nonpathologic bacteria on the skin, usually the chromogenic Corynebacterium, and this chemical reaction causes blue or sometimes black or red discoloration in patchy areas on the skin. It also can result from the reaction between the sweat and other pathogens such as Bacillus species and certain fungi (Piedraria), dyes, drugs (Rifampin), and other chemicals (copper).7 Wiping the skin with an alcohol pad usually makes the diagnosis.
Pseudochromhidrosis has to be differentiated from chromhidrosis (Greek for “colored sweat”), which is an even more unusual condition characterized by the secretion of colored sweat, because it has several more ominous causes. There are 2 forms of chromhidrosis, dependent on the origin of the colored sweat from apocrine or eccrine glands.
Apocrine chromhidrosis is usually facial, but can occur wherever apocrine glands are present, including the nipples, axilla, and anal areas. Yellowish brown lipofuscin pigment is responsible for the colored sweat when there is a higher oxidative stress in the apocrine glands. This condition is usually idiopathic, and the color of the sweat depends on the oxidation of the lipofuscin, including yellow, blue, brown, green, or black. Diagnosis can be made by performing a skin biopsy looking at the presence of lipofuscin granules or autofluorescence of sweat, skin specimens, or clothing under a Wood lamp.
In contrast, eccrine chromhidrosis occurs with ingestion of certain dyes or drugs, some deadly. Dyes such as bromophenol blue, which is used as an acid-base indicator or dye, can be fatal with ingestion. The ingestion of copper salts, used as a fungicidic agent, also can cause discoloration of the skin, but now is considered too toxic. However, copper salts are found in children’s chemistry sets and used to grow crystals. Identification of copper salts via thorough patient history can determine if ingestion has occurred.
The distinction between pseudochromhidrosis and apocrine or eccrine chromhidrosis is vitally important for treatment and prognosis.
Pseudochromhidrosis usually responds to treatments that eliminate the bacteria on the skin, such as chlorhexidine scrubs, topical antibiotics, and, rarely, oral antibiotics.
There is no known treatment for the accumulation of lipofuscin, so in apocrine chromhidrosis the treatment is geared toward decreasing sweat using 20% aluminum chloride hexahydrate (Drysol), topical capsaicin (a topical cream made from hot peppers), or injections of botulism toxin (Botox). Definitive treatment of chromhidrosis is surgical excision of the affected apocrine sweat glands.8-14
Treatment of eccrine chromhidrosis consists of identifying and eliminating the ingestion of the soluble pigment.
The patient in this case was the daughter of author Daniel Taylor, MD. The night of the ED visit, he received an e-mail from his coauthor Dana Toib, MD, who is a pediatric rheumatologist, with the subject line “green fingers.” The fingers discoloration spared the palms and interdigital space, making vasospasm, vascular occlusion, hypoxemia, and methemoglobinemia unlikely. This raised the suspicion that the blue discoloration of the girl’s hands was a result of skin discoloration, in particular, pseudochromhidrosis. The e-mail included a description of pseudochromhidrosis and how to diagnose it using a wet alcohol pad.
It was late at night, so Dr. Taylor waited until sunrise, cloth soaked with alcohol in hand, to wake his daughter. “What are you doing?” she asked him as he hovered over her bed. “Trust me,” he said as he wiped the cloth hard across her knuckles. The color that had mystified his daughter, her school, and the ED physician transferred easily onto the cloth, and he continued to wipe away the blue coloration from her hands until it all was removed. He cancelled her specialist appointments, thanked his coauthor for her e-mail, and bought some antibacterial hand wipes in preparation for his daughter’s next oral presentation.
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