Only special multi-wawelength oximeters (CO-oximeters) can detect methemoglobinemia directly. When there is a "saturation gap" between a low ordinary pulse oximeter reading and a high arterial blood gas analysis result, methemoglobinemia may be suspected. Liver
Toxic hepatitis and cholestatic jaundice have been reported by the manufacturer. These toxic reactions may also occur as part of the dapsone hypersensitivity syndrome (a form of SCARs-see above) or dapsone syndrome (see below). Dapsone is metabolized by the Cytochrome P450 system, specifically isozymes CYP2D6, CYP2B6, CYP3A4, and CYP2C19. Dapsone metabolites produced by the cytochrome P450 2C19 isozyme are associated with the methemoglobinemia side effect of the drug. Skin
When used topically, dapsone can cause mild skin irritation, redness, dry skin, burning, and itching. When used together with benzoyl peroxide products, temporary yellow or orange skin discolorations can occur. Dapsone hypersensitivity syndrome
Hypersensitivity reactions occur in some patients. This reaction may be more frequent in patients receiving multiple-drug therapy.The reaction always involves a rash, may also include fever, jaundice, and eosinophilia, and is likely to be one manifestation of the SCARs reaction viz., the DRESS syndrome (see above). In general, these symptoms will occur within the first six weeks of therapy or not at all, and may be ameliorated by corticosteroid therapy. Other adverse effects
Other adverse effects include nausea, headache, and rash (which are common), and insomnia, psychosis, and peripheral neuropathy. Effects on the lung occur rarely and may be serious, though are generally reversible.
In climbers who had previously developed HAPE, re-attack rate was up to 60% with ascent to 4,559 metres (14,957 ft) in a 36-hour time period, though this risk was significantly reduced with slower ascent rates. It is believed that up to 50% of people suffer from subclinical HAPE with mild edema to the lungs but no clinical impairment. History
HAPE was recognized by physicians dating back to the 19th century but was originally attributed to “high altitude pneumonia”. The first documented case of pulmonary edema, confirmed by autopsy, was probably that of Dr Jacottet who died in 1891 in the Observatoire Vallot below the summit of Mont Blanc. After participating in a rescue on the mountain, the doctor refused to return. Instead, he spent further two nights at an altitude of 4,300 metres (14,100 ft) with obvious AMS symptoms and died on the second night. This condition was subsequently noticed in otherwise healthy climbers who would die shortly after arriving at high altitudes. It was not until 1960 that Charles Houston, an internal medicine physician in Aspen, published a case report of 4 individuals participating in high elevation activities that he had diagnosed with “edema of the lungs”. He described chest X-rays with edema and non-specific changes on EKG. Even though these cases had been termed high altitude pneumonia in the past, Houston indicated that these cases were “acute pulmonary edema without heart disease”. Research
To help understand factors that make some individuals susceptible to HAPE, the International HAPE Database was set up in 2004.