Quiz Page March 2010:
Pruritus in Advanced CKD
Article Outline
Clinical Presentation
A 55-year-old man with a history of hypertension, type 2 diabetes, and advanced chronic kidney disease (CKD) presented with generalized pruritus for > 6 months. The patient had no history of allergic or atopic disease. Physical examination showed generalized xerosis and hyperpigmentation of the trunk (Fig 1). No papules, pustules, or vesicles were noted, but hyperkeratosis and heavy crusting were present on both palms (Fig 2). Routine blood tests showed the following values: urea nitrogen, 49 mg/dL (17.4 mmol/L); serum creatinine, 5.3 mg/dL (468.5 μmol/L, estimated glomerular filtration rate, 12.5 mL/min/1.73 m2 [0.21 mL/s/1.73 m2]); calcium, 9.2 mg/dL (2.3 mmol/L); phosphate, 5.2 mg/dL (1.6 mmol/L); and hemoglobin, 6.4 g/dL (64 g/L). Despite treatment with topical emollients, oral antihistamine, and UV-B light therapy, there was no improvement in pruritus. Additional blood tests showed a white blood cell count of 16.1 × 103/μL (16.1 × 109/L), eosinophil count of 5,876/μL (36.5%; normal, <5%), and an extremely high immunoglobulin E (IgE) level of 11,500 IU/mL (normal range, 0-100 IU/mL). C-reactive protein returned at 10.9 mg/L (normal range, <5 mg/L).
Figure 1.
Photograph of trunk.
Figure 2.
Photograph of hands.
■ What are the causes of pruritus in patients with advanced CKD?
■ What is the pathogenesis of pruritus in patients with late-stage kidney disease?
■ How should pruritus be evaluated in this patient?
■ What is your clinical diagnosis?
Discussion
What are the causes of pruritus in patients with advanced CKD?
The prevalence of pruritus in patients with CKD ranges from 22%-90%.1 The cause of pruritus can be classified as dermatologic, systemic, neurogenic/neuropathic, psychogenic, or a combination of these factors. Diagnostic criteria for uremic pruritus include the following: (1) pruritus that develops in the setting of kidney failure or dialysis treatment, and (2) ≥ 3 episodes of itch that trouble the patient for 14 days, with each episode lasting for several minutes.2 Some uremia-unrelated conditions, such as drug-induced hypersensitivity, hepatitis, hypothyroidism, iron deficiency anemia, malignancy, or specific skin disorders, should be considered in the differential diagnosis of CKD-associated pruritus.3
What is the pathogenesis of pruritus in patients with late-stage kidney disease?
The pathogenesis of pruritus is not well understood, but likely involves the immunologic and opioidergic systems. A proinflammatory state resulted from an immune derangement and imbalance in the endogenous opioidergic system can result in pruritus.1 Abnormal patterns of cutaneous innervations also may have a role in CKD-associated pruritus. Mast cells in the dermis release histamine and hence can stimulate C-terminal nerve endings to induce itch. Several other factors are implicated in the pathogenesis of CKD-associated pruritus, such as xerosis and high levels of serum phosphate, parathyroid hormone, magnesium, aluminum, and substance P. Other considerations include hypervitaminosis A and peripheral neuropathy.3
How should pruritus be evaluated in this patient?
Although treatment of pruritus in patients with CKD usually is difficult, the atypical dermatologic presentation with eosinophilia and increased IgE levels in this patient prompted some other considerations. The possible conditions associated with eosinophilia and increased IgE levels include parasite infections or certain types of fungal infections, allergic or atopic diseases, hematologic and neoplastic disorders, or immunodeficiency diseases. Skin biopsy is a diagnostic tool if the cause can not be determined clinically.
What is your clinical diagnosis?
Skin biopsy of the right palm was performed. Parakeratosis, with many scabies mites, marked acanthosis, mild exocytosis, papillomatosis, and mild perivascular mononuclear cell infiltrates with eosinophils in the dermis were noted (Fig 3). Crusted scabies was diagnosed.
Figure 3.
Cross-section of a mite in the stratum corneum with marked acanthosis and parakeratosis (hematoxylin and eosin stain; original magnification, ×400).
Crusted scabies is a rare variant of classic scabies and is highly contagious. Usually, an average of only 10-15 living mites will be found in a patient with classic scabies. However, crusted scabies is characterized by infestation of thousands to millions of mites and the development of hyperkeratotic skin crust in an acral distribution. It usually is far less pruritic than classic scabies, and burrows may be limited or absent. An impaired cell-mediated immune response, also seen in patients with CKD, is considered an important risk factor for crusted scabies.4
Eosinophilia is associated with classic scabies. In addition, an extremely elevated IgE level recently has been noted in crusted scabies. In a large case series, eosinophilia and increased IgE levels occur in 58% and 96% of patients with crusted scabies, respectively.5 In our patient, eosinophilia and a high IgE level gave us hints to search for other causes specific to the itch.
Final Diagnosis
Crusted scabies in a patient with CKD.
Acknowledgements
The authors thank Li-Chun Ho, MD, for assistance with this article.
References
- . An update on pruritus associated with CKD. Am J Kidney Dis. 2007;50(1):11–20
- . Dermatological disease in patients with CKD. Am J Kidney Dis. 2008;51(2):331–344
- . Uremic pruritus. Kidney Int. 2007;72(3):373–377
- . Crusted scabies: a clinical review. J Drugs Dermatol. 2006;5(3):221–227
- Crusted scabies: clinical and immunological findings in seventy-eight patients and a review of the literature. J Infect. 2005;50:375–381
Case provided and authored by Min-Yu Chang, MD, Hsi-Hao Wang, MD, Yi-Jer Lee, MD, and Shih-Yuan Hung, MD, Division of Nephrology, Department of Medicine, E-Da Hospital/I-Shou University, Kaohsiung County, Taiwan, ROC.
Address correspondence to Shih-Yuan Hung, MD, Division of Nephrology, Department of Internal Medicine, E-Da Hospital/I-Shou University, No. 1, Yi-Da Rd, Jiau-shu Tsuen, Yan-chau Shiang, Kaohsiung County, Taiwan, ROC. E-mail: ed101366@edah.org.tw
Support: None.
Financial Disclosure: None.
PII: S0272-6386(09)01259-1
doi:10.1053/j.ajkd.2009.09.010
© 2010 National Kidney Foundation, Inc. Published by Elsevier Inc All rights reserved.
