Pruritus Group A2

Pathophysiology of pruritus The sensation of pruritus is transmitted through slow-conducting unmyelinated C-polymodal and possibly type A delta nociceptive neurons with free nerve endings located near the dermoepidermal junction or in the epidermis. These neurons appear to be located more superficially and are more sensitive to pruritogenic substances than pain receptors. Activators of these nerves include histamine, neuropeptide substance P, serotonin, bradykinin, proteases (eg, mast cell tryptase), and endothelin (which stimulates the release of nitric oxide). Impulses are transmitted from the dorsal root ganglion to the spinothalamic tract and eventually to the thalamus.

Type of Pruritus According to the Body Site Localized pruritus Generalized pruritus Senile pruritus

Pruritus and Systemic Disease

1- Renal pruritus : Renal pruritus can occur in patients with chronic renal failure (CRF) and is most often seen in patients receiving hemodialysis (HD). This term is synonymous with uremic pruritus; however, the condition is not due to elevated serum urea levels. The actual pruritogenic substance has yet to be identified

2- Cholestatic Pruritus: Cholestasis or a decrease or arrest in the flow of bile, is associated with pruritus. The deposition of bile salts in the skin was thought to directly cause a pruritogenic effect. Pruritus is more common with intraheptic cholestasis than extrahepatic cholestasis. 

3- Hematologic pruritus Iron is a critical factor in many enzymatic reactions. Although iron deficiency has not been proved to be a cause of pruritus, it may contribute to pruritus through a variety of metabolic paths. Patients with pruritus and iron deficiency may not be anemic; this observation suggests that pruritus may be related to iron and not hemoglobin.  Patients with polycythemia vera have increased numbers of circulating basophils and skin mast cells, which have been correlated with itching. The itch typically occurs during cooling after a hot shower.

4- Endocrine pruritus Hyperthyroidism has been associated with pruritus. Excess thyroid hormone may activate kinins from increased tissue metabolism or may reduce the itch threshold as a result of warmth and vasodilation. Hypothyroidism is also implicated because pruritus is likely secondary to xerosis. Diabetes mellitus  is another possible cause, but cause and effect remain unproven. Metabolic abnormalities, autonomic dysfunction, anhydrosis, and diabetic neuropathy all may contribute.

5- Pruritus and malignancies Numerous reports have linked pruritus to almost every type of malignancy. Release of toxins and the immune system have been suggested to play roles in malignancy-related pruritus. In patients with Hodgkin lymphoma ; leukopeptidase and bradykinin appear to be the pruritogenic mediators released as an autoimmune response is mounted against malignant lymphoid cells. Opioids are known to modulate the sensation of pruritus, both peripherally and centrally. Stimulation of opioid mu receptors accentuates pruritus, while stimulation of kappa receptors and blockage of mu receptors suppress pruritus.

General management measures of pruritus

1- General measures Patient education Liberal use of moisturizers Reduce frequency of bathing/use lukewarm water, not hot Avoid soap (use soap substitute instead) Avoid irritating fabrics (cotton or silk are recommended) Avoid vasodilators (caffeine, alcohol, spices, hot water) Keep fingernails short

2- Topical Treatments Simple emollient creams and ointments Antipruritic emollients Cooling emollients, such as 1% menthol in aqueous cream Soap substitutes Sodium bicarbonate (added to bath water) Topical corticosteroids ( prednisolone – dexamethasone )  Doxepin cream Capsaicin cream

3- Systemic Treatments 1- Oral antihistamine: Diphenhydramine – hydroxyzine Prescribed in a sedative dose at bedtime is effective in producing a restful comfortable sleep. 2- Antidepressants : Doxepin For pruritus of neuropsychogenic origin. 3- Treating the underlying diseases.

4- Physical Treatment - Light therapy: Phototherapy involves exposing the skin to certain wavelength of ultraviolet light. Multiple sessions are usually scheduled until the itching is under control.