Importance of Assessing Serum Electrolytes in Dermatology: A Road Map from Blood Reports

Introduction Electrolytes are minerals essential for the proper functioning of our body’s cardiac, nervous, and musculoskeletal system. Although less known for skin diseases, various dermatological conditions result in severe electrolyte imbalance and may lead to serious complications. Electrolytes help to maintain electrical neutrality in cells and generate and conduct action potentials in nerves and muscles. The cationic electrolytes include sodium (Na+), potassium (K+), calcium (Ca2+), and magnesium (Mg2+); anionic electrolytes include chloride (Cl-), bicarbonates (HCO3-), and phosphates (PO42-). High or low levels of electrolytes impair body functions and can lead to life-threatening complications. Hence, dermatologists should be aware of the importance of electrolytes so that appropriate measures can be taken to prevent morbidity and death. Sometimes, these investigations play an essential role in assessing the severity of diseases or prognostic implications and diagnosing dermatological diseases. Electrolytes also should be measured while prescribing certain drugs used for some dermatological diseases and in their long-term follow-up. In this article, we present a brief report of crucial electrolytes, their optimum level for the proper functioning of our body, and their implications for skin diseases. Specific Electrolytes Sodium (Na+) Sodium has a central role in maintaining extracellular fluid volume. It also has a role in regulating the membrane potential of cells. In active transport, sodium is exchanged with potassium across cell membranes.[1] Sodium transport occurs via sodium-chloride symporters, which are controlled by the hormone aldosterone.[2] The usual range of sodium is 135 to 145 mmol/L. Hyponatremia is when serum sodium level is below 135 mmol/L. Patients generally present with headache, confusion, nausea, and delirium.[3] Hypernatremia occurs when serum sodium level exceeds 145 mmol/L. Hypernatremia presents as tachypnoea, sleeping difficulty, and restlessness. Mild to moderate hypernatremia is when sodium level is within 145 to 160 mmol/L, and severe hypernatremia is considered when sodium level is more than 160 mmol/L.[4] Hyponatremia Many acute skin failure conditions cause deranged Na+ levels, which can be suspected by symptoms of hypo- or hypernatremia and diagnosed by serum Na+ levels. Assessment of sodium levels should be followed strictly until a correction is made. The common skin conditions include erythroderma, exfoliative drug reactions, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) [Table 1].[5] In SJS-TEN, the sodium level is decreased due to the loss of barrier and excess trans-epidermal loss. SJS-TEN patients lose a lot of fluid, in the form of blister fluid and insensible fluid loss. An adult patient may lose approximately 3–4 L of fluid in a day in case of 50% body surface area involvement. The loss of electrolytes such as sodium, potassium, and chloride in blister fluid usually accompanies this. Hyponatremia (serum sodium less than 120 mmol/L) is a prognostic parameter in the SCORTEN score. Addison’s disease presents as hyperpigmentation of the skin, palmar crease, and axilla and also has serum electrolyte disturbances like hyposmolar hyponatremia and hyperkalemia.[6] Additional levels of adrenocorticotropic hormone, renin, and low serum cortisol are required to confirm Addison’s disease. Severe hyponatremia has been reported as the initial presentation of late-onset Schmidt’s syndrome.[7] Schmidt’s syndrome (autoimmune polyglandular syndrome) manifests as autoimmune Addison’s disease and hypothyroidism in young adults. Uncommonly, hyponatremia has been reported in scleroderma renal crisis[8] as a complication due to activation of the renin-angiotensin pathway in scleroderma. There are also a few case reports of hyponatremia in dermatomyositis.[9] Dermatomyositis accompanied by hyponatremia-induced rhabdomyolysis, confusing the cause of muscle weakness, has been reported.[10] Hyponatremia in the absence of any renal insufficiency or adrenal insufficiency in mostly hospitalised patients should raise suspicion of syndrome of inappropriate antidiuretic hormone secretion (SIADH). Few cutaneous tumours like malignant melanoma[11] and Merkel cell carcinoma[12] may have SIADH as a paraneoplastic presentation. SIADH as a complication of drug rash with eosinophilia and systemic symptoms has been reported.[13] Table 1: Emergencies in dermatology necessitating serum electrolyte measurementHypernatremia The hypernatremic state in TEN patients may also lead to increased mortality.[14] Iatrogenic hypernatremia is a reliable marker of systemic dehydration in these patients. Increased serum sodium concentration leads to higher skin sodium levels and may aggravate psoriasis and atopic dermatitis.[15] Increased level of Na+ concentration enhances IL-17 expression among CD4 T-cells, resulting in disease severity. Miliaria crystallina may rarely develop in newborns with severe hypernatremia.[16] Several neonatal dermatoses[17] that may be associated with skin failure or increased transepidermal water loss, causing hyper- or hyponatremia, have been depicted in Table 2. Table 2: Neonatal skin diseases necessitating serum electrolytes measurementPotassium (K+) Potassium is mainly an intracellular ion. The sodium-potassium adenosine triphosphatase transporter pumps sodium in exchange for potassium in cells. Aldosterone increases potassium secretion.[18] Potassium channels and potassium-chloride co-transporters at the apical tubular membrane also secrete potassium.[19] Typical values range from 3.6 to 5.5 mmol/L. Hypokalemia and Hyperkalemia Hypokalemia is defined as serum potassium levels below 3.6 mmol/L. It clinically manifests as weakness, fatigue, and muscle twitching.[20] Serum potassium levels of more than 5.5 mmol/L lead to hyperkalemia and arrhythmias. Symptoms include muscle cramps, muscle weakness, rhabdomyolysis, and myoglobinuria.[21] Hypokalemia may also cause skin dryness and rashes. Hyponatremia is usually associated with hyperkalemia in skin failure conditions. Sudhakar et al.[22] found reduced serum potassium levels in psoriasis patients. A high serum potassium level was also found in Addison’s disease.[6] Calcium (Ca2+) Calcium is also an essential electrolyte. It maintains the bone health. 1,25-dihydroxy vitamin D3 has a prominent role in intestinal calcium absorption. In distal tubules of the kidney, calcium secretion is regulated by parathyroid hormone.[23] Blood calcium level is decreased by the action of calcitonin on bone cells. Normal serum calcium range is 8.8 mg/dL to 10.7 mg/dL.[4] Serum albumin levels should always be corrected before diagnosing hypocalcemia. Hypocalcemia is corrected serum total calcium levels below 8.8 mg/dL. Vitamin D deficiency or hypoparathyroidism is the leading cause of hypocalcemia. Hypercalcemia is when the total corrected serum calcium level is above 10.7 mg/dL, mainly due to primary hyperparathyroidism. In dystrophic calcifications, serum calcium levels are normal compared to metastatic calcifications, which have elevated serum calcium levels. Hypercalcemia Hypercalcemia can lead to calcinosis cutis (calcium deposits in the skin) and pruritus. Subcutaneous fat necrosis of newborns may be associated with a potential life-threatening hypercalcemia.[24] Serum calcium concentration increase leads to nephrocalcinosis, reduced renal function, and calcification in the skin, gastric mucosa, and myocardium.[24] In sarcoidosis, there are hypercalcemia and hypercalciuria, which should be addressed to prevent chronic organ failure. Serum calcium level >1.23 mmol/L is a specific indicator for extrapulmonary sarcoidosis.[25] Hypocalcemia It is associated with perioral numbness and tingling and can sometimes present with dermatitis. Calcium plays a vital role in the proliferation and differentiation of keratinocytes. Hypocalcemia can damage cell adhesion molecules, such as cadherins, leading to keratinocyte hyperproliferation and aggravation of psoriasis.[26] The pustular psoriasis of von Zumbusch is associated with hypocalcemia,[27] As noted by Morimoto et al.,[28] there is a strong association between low serum calcium levels and the severity of skin lesions in psoriasis vulgaris. Hypocalcemia is also found in patients with erythroderma, psoriatic arthritis, and pustular psoriasis. Magnesium (Mg2+) Magnesium is an intracellular cation. It is vital in adenosine triphosphate metabolism, proper muscle functioning, neurological functioning, and neurotransmitter release.[29] Hypomagnesemia occurs when the serum magnesium level is below 1.46 mg/dL. Alcohol use, gastrointestinal conditions, and excessive renal loss may result in hypomagnesemia. It commonly presents with ventricular arrhythmias, which include torsades de pointes. Hypomagnesemia may also result from the use of certain medications, such as omeprazole.[30] Hypomagnesemia can lead to muscle spasms and skin changes, including chronic pruritus and eczematous dermatitis. Chloride (Cl-) Chloride is an extracellular fluid anion. Chloride is mainly filtered by the glomerulus and is reabsorbed by proximal and distal tubules through active and passive transport.[31] Hyperchloremia can occur due to gastrointestinal bicarbonate loss. Hypochloremia presents in gastrointestinal losses like vomiting or excess water gain like congestive heart failure. Chloride is immune-boosting in inflammatory skin conditions like rosacea, eczema, psoriasis, and acne vulgaris (stage-2 and 3). Sweat chloride measurement is essential in the diagnosis of cystic fibrosis. Imbalance of sodium and chloride levels may occur in acute skin failure conditions. Phosphate (PO4-2) Phosphorus is an extracellular fluid anion. Bones and teeth have 85% of the total body phosphorus in the form of hydroxyapatite; the remaining 15% is found in the soft tissues. Phosphate has a vital role in metabolic pathways. Vitamin D3, parathyroid hormone, and calcitonin regulate phosphate simultaneously with calcium. The kidneys have a significant role in phosphorus excretion. Metastatic calcinosis cutis is associated with hyperphosphatemia. Hyperphosphataemic familial tumoral calcinosis is associated with high serum phosphate levels.[32] It is the hereditary counterpart of acquired metastatic calcification, which results from mutations in FGF23 and GALNT3 genes. Hyperphosphatemia can also lead to calciphylaxis. Bicarbonate (HCO3-) The bicarbonate levels in serum are decided by serum acid-base status. The kidneys are vital in regulating bicarbonate concentration and maintaining the acid-base balance.[33] In SJS/TEN patients, serum bicarbonate is measured at the time of hospitalisation to prognosticate patients as per SCORTEN criteria [Table 3] High serum bicarbonate is induced iatrogenically during the management of methotrexate poisoning to alkalinise urine and facilitate methotrexate excretion. Table 3: SCORTEN ScoreDrugs and electrolytes Measuring serum electrolytes while prescribing various drugs[34] for different dermatological diseases is essential [Table 4].Table 4: Electrolyte imbalance caused by drugs used in dermatology[ 34 ]Conclusion A basic knowledge of various serum electrolytes and their recommended dietary allowances [Table 5] is needed to monitor for optimal disease management, estimating prognosis, and balancing drug side effects. Managing electrolyte levels should be a part of a holistic approach to treat dermatological conditions. Estimating serum electrolytes has prognostic values in many skin conditions like pustular psoriasis or acute skin failure (SJS-TEN). A periodic estimation of serum electrolytes is also needed for patients with skin failure and those on certain medications.[35]Table 5: Recommended dietary allowances of important electrolytesFinancial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.