What causes a rash after Acute Kidney Injury (AKI) or liver elevations?

From the Guidelines

Rashes after Acute Kidney Injury (AKI) or liver elevations are primarily caused by the buildup of uremic toxins, medication reactions, or immune system dysregulation, necessitating prompt treatment of the underlying condition and management of symptoms. The pathophysiology involves the accumulation of waste products like urea in AKI, leading to uremic frost or pruritus, and subsequent scratching that results in excoriations and rash 1. Similarly, liver dysfunction can cause jaundice with associated pruritus and scratching-induced rashes, or cholestasis that triggers pruritic skin manifestations.

Key Causes and Management

• Uremic toxin buildup: Accumulated waste products like urea can cause uremic frost or pruritus with subsequent scratching leading to excoriations and rash.
• Medication reactions: Medications used to treat AKI or liver elevations, such as antibiotics, diuretics, or pain medications, can cause allergic reactions presenting as rashes.
• Immune system dysregulation: Both kidney and liver dysfunction can alter drug metabolism, increasing the risk of adverse cutaneous reactions even at standard doses, and trigger inflammatory skin conditions.
• Management: Typically involves treating the underlying organ dysfunction, discontinuing offending medications, providing symptomatic relief with antihistamines like diphenhydramine (25-50mg every 6 hours) or hydroxyzine (25mg every 6 hours), and using topical corticosteroids like hydrocortisone 1% for localized rashes, as suggested by recent clinical practice updates 1.

Clinical Approach

Given the complexity of AKI and liver elevations, a careful history, physical examination, blood biochemistry, urine microscopic examination, urine chemistry, and selected urinary biomarkers, along with renal ultrasound, are crucial for determining the cause of AKI 1. This comprehensive approach helps in identifying the specific type of AKI, whether it's due to hypovolemic causes, acute tubular necrosis, hepatorenal syndrome, or postrenal causes, and guides the management strategy accordingly. Early recognition and treatment of the underlying cause, along with symptom management, are critical in improving outcomes and quality of life for patients with rashes following AKI or liver elevations.

From the FDA Drug Label

The incidence of skin rash may be increased in the presence of renal insufficiency. Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome or drug hypersensitivity syndrome (DHS) has been reported in association with allopurinol use. The syndrome includes many of the severe reactions described above, and is potentially life-threatening and fatal The syndrome is often characterized by fever, severe and profuse skin rash, elevated leukocyte counts and in particular, elevated eosinophil counts, lymphadenopathy, and multi-organ pathologies. Systemic symptoms often included, but were not limited to, the hepatic and renal systems

The rash after Acute Kidney Injury (AKI) or liver elevations may be caused by a hypersensitivity reaction to the drug, which can be increased in the presence of renal insufficiency. The reaction can manifest as a skin rash, and in severe cases, can progress to DRESS syndrome or drug hypersensitivity syndrome, which can be life-threatening and fatal 2.

• Key factors that may contribute to the development of a rash include:
  • Renal insufficiency
  • Liver disease
  • Hypersensitivity reaction to the drug
  • Concomitant use of other medications, such as thiazides 2
• Clinical presentation may include:
  • Skin rash
  • Fever
  • Elevated leukocyte counts
  • Elevated eosinophil counts
  • Lymphadenopathy
  • Multi-organ pathologies

From the Research

Causes of Rash after Acute Kidney Injury (AKI) or Liver Elevations

• A rash after AKI or liver elevations can be caused by various factors, including allergic reactions to certain medications, such as allopurinol 3.
• Allopurinol-induced toxic epidermal necrolysis (TEN) is a rare but potentially severe adverse effect that can cause a rash, as well as acute renal failure and cholestatic jaundice 3.
• Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is another rare but potentially fatal adverse drug reaction that can cause a rash, as well as AKI and liver elevations 4.
• The exact mechanism of how AKI or liver elevations cause a rash is not fully understood, but it is thought to be related to the release of inflammatory mediators and the activation of immune cells 3, 4.

Medications that Can Cause a Rash after AKI or Liver Elevations

• Allopurinol is a medication that can cause a rash, as well as AKI and liver elevations, due to its potential to induce allergic reactions and hypersensitivity 3, 4.
• Other medications that can cause a rash after AKI or liver elevations include those that are known to be nephrotoxic or hepatotoxic, such as certain antibiotics and anti-inflammatory drugs 5.

Diagnosis and Management of Rash after AKI or Liver Elevations

• The diagnosis of a rash after AKI or liver elevations typically involves a thorough history and physical examination, as well as laboratory tests to determine the underlying cause 6, 5.
• Management of a rash after AKI or liver elevations typically involves discontinuing any offending medications, as well as providing supportive care measures such as fluid resuscitation and nutritional support 5.
• In severe cases, such as allopurinol-induced TEN, aggressive immunosuppressive therapy and intensive care management may be necessary 3.