Immersion foot syndromes are a class of foot injury caused by water absorption in the outer layer of skin. There are different subclass names for this condition based on the temperature of the water to which the foot is exposed. These include trench foot, tropical immersion foot, and warm water immersion foot. : 26–7  In one 3-day military study, it was found that submersion in water allowing for a higher skin temperature resulted in worse skin maceration and pain. Causes
Trench foot
Trench foot  is a medical condition caused by prolonged exposure of the feet to damp, unsanitary, and cold conditions. The use of the word trench in the name of this condition is a reference to trench warfare, mainly associated with World War I. Affected feet may become numb, affected by erythrosis (turning red) or cyanosis (turning blue) as a result of poor vascular supply, and feet may begin to have a decaying odour due to the possibility of the early stages of necrosis setting in. As the condition worsens, feet may also begin to swell. Advanced trench foot often involves blisters and open sores, which lead to fungal infections; this is sometimes called tropical ulcer (jungle rot). If left untreated, trench foot usually results in gangrene, which can cause the need for amputation. If trench foot is treated properly, complete recovery is normal, though it is marked by severe short-term pain when feeling returns. As with other cold-related injuries, trench foot leaves those affected more susceptible to it in the future.
Adverse effects
Voclosporin has a boxed warning for malignancies and serious infections. Patients taking Voclosporin along with other immunosuppressants have an increased risk for developing malignancies and serious infections that may lead to hospitalization or death. The most common adverse reactions of voclosporin were (>3%), glomerular filtration rate decreased, hypertension, diarrhea, headache, anemia, cough, urinary tract infection, abdominal pain(upper), dyspepsia, alopecia, renal impairment, abdominal pain, mouth ulceration, fatigue. tremor, acute kidney injury, and decreased appetite. Pharmacology
Voclosporin is a cyclosporin A analog, similar to cyclosporin A with modifications on an amino acid within one region that allows the drug to bind to Calcineurin. Voclosporin inhibits calcineurin, which then blocks the production of IL-2 and T-cell mediated immune responses. As a result of the calcineurin inhibition, podocytes (cells within the kidneys) are stabilized while inflammation is reduced. Reduction of inflammation within the kidneys prevents further renal damage. Pharmacokinetics
When administered on an empty stomach, the median Tmax of voclosporin is 1.5 hours. The AUC is estimated to be 7693 ng/mL and the Cmax  is estimated at 955 ng/mL. The volume of distribution is approximately 2,154 L and distributes within the red blood cells. The distribution between the plasma and whole blood is affected by temperature and concentration. The protein binding of voclosporin is 97%. The average terminal half-life of voclosporin is 63.6 L/h. The drug is mainly metabolized by the CYP3A4 hepatic cytochrome enzyme. Pharmacologic activity is mainly attributed to the parent molecule itself, with the major metabolite being 8-fold less potent than the parent drug.