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Pruritus A manifestation of systemic disease
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  1. Pruritus A manifestation of systemic disease • Dr : Rabie Fahmy Zahran. • Tropical M. Consultant. • Damietta Fever Hospital. • Egypt. rabiezahran@gawab.com 0124114646

  2. Pruritus An unpleasant localized or generalized sensation on the skin, mucus membranes or conjunctivae which the patient unconsciously attempts to relieve by scratching or rubbing. It is a common manifestation of many dermatological conditions , but may also results from systemic diseases. rabiezahran@gawab.com 0124114646

  3. Diversity of Causes and Presentation Causes may be : Trivial to Life threatening (mosquito bite) (malignancy) *Localized itching rarely caused by systemic disease. rabiezahran@gawab.com 0124114646

  4. *up to 50% of cases with generalized itching without obvious dermatological cause have systemic disease. rabiezahran@gawab.com 0124114646

  5. Poorly Understood & Managed • Relies on similar components of the pain system: receptors, neurotransmitters, spinal pathways and centers in the brain • Stimulating pain can relief itching • Treating pain with some analgesics relieves itching, others trigger itching • Pruritus is a common side-effect of opioid administration, sometimes worse than the pain rabiezahran@gawab.com 0124114646

  6. Pruritogenic Stimuli • Pressure • Low-intensity electrical or punctatestimuli. • Histamine: acts directly on free nerve endings in skin rabiezahran@gawab.com 0124114646

  7. Pain vs Itch Nerves • Itch transmitted from specialized pain receptors: a subclass of C-nociceptors • Mechano-insensitive • Histamine sensitive • Nerve endings cluster around “itch points” which correspond to areas very sensitive to pruritogenic stimuli rabiezahran@gawab.com 0124114646

  8. Itch pathways • Fibers originate @ dermal/epidermal jxn  • Thin unmyelinated axons, lots of branching  • Ipsilateral dorsal horn of spinal cord  • Synapse with itch-specific secondary neurons • Cross to opposite anterolateral spinothalamic tract to thalamus  • Somatosensory cortex of postcentral gyrus • SLOW transmission and BROAD receptor field rabiezahran@gawab.com 0124114646

  9. rabiezahran@gawab.com 0124114646

  10. Histamine. Prostaglandins. Leukotrienes. Serotonin. Acetylcholine. Substance P Proteases. Peptides. Enzymes. Cytokines. Itch Mediators rabiezahran@gawab.com 0124114646

  11. rabiezahran@gawab.com 0124114646

  12. *Itching is a common complaint that may reflect underlying systemic disease. *General practitioners are equipped to identify the more common cutaneous and non-cutaneous causes of itching. rabiezahran@gawab.com 0124114646

  13. * Dermatology consultation may be warranted if the diagnosis is unclear or the condition does not respond to treatment. rabiezahran@gawab.com 0124114646

  14. Evaluation of a patient complaining of itch rabiezahran@gawab.com 0124114646

  15. The first step rabiezahran@gawab.com 0124114646

  16. The first step is to : Determine if it is caused by a skin condition or a systemic disease . The physician should attempt to identify primary skin lesions or any evidence of infestation. It is excellent not to miss the diagnosis of the Ten major dermatological causes of pruritus . rabiezahran@gawab.com 0124114646

  17. Ten major dermatological causes of pruritus Scabies. Dermatitis herpetiformis . Atopic dermatitis. Lichen simplex chronicus. Bullous pemphigoid. Drug hypersensitivity. Urticaria. Xerosis (winter itch). Mycosis fungoides. Psoriasis. rabiezahran@gawab.com 0124114646

  18. (1) Scabies skin exam. may reveals burrows . rabiezahran@gawab.com 0124114646

  19. (2) Dermatitis herpetiformis pruritic autoimmune blistering disorder associated with a gluten-sensitive enteropathy (GSE). characterized by grouped excoriations; erythematous, urticarial plaques; and papules with vesicles. Common sites: extensor surfaces of the elbows, knees, buttocks, and back. rabiezahran@gawab.com 0124114646

  20. (4) Atopic dermatitis • pruritic disease of unknown origin . • starts in early infancy (an adult-onset variant is recognized); • it is characterized by pruritus, eczematous lesions,xerosis, thickening of the skin. • may be associated with other atopic diseases (eg, asthma, allergic rhinitis, urticaria, acute allergic reactions to foods). rabiezahran@gawab.com 0124114646

  21. (4) Lichen simplex chronicus pruritic plaques with thickening of the skin occurs on any location : *Scalp *Nape of neck *Extensor forearms and elbows *Vulva and scrotum. *Upper medial thighs, *knees, *lower legs, *ankles rabiezahran@gawab.com 0124114646

  22. (5) Bullous pemphigoid • chronic, autoimmune, subepidermal, blistering skin disease that rarely involves mucous membranes. • characterized by the presence of immunoglobulin G (IgG) auto-antibodies • precipitated by ultraviolet irradiation, x-ray therapy, and exposure to some drugs. • Like: furosemide, ibuprofen and other nonsteroidal anti-inflammatory agents, captopril, penicillamine, and antibiotics. rabiezahran@gawab.com 0124114646

  23. (6) Drug hypersensitivity rabiezahran@gawab.com 0124114646

  24. (7) Urticaria rabiezahran@gawab.com 0124114646

  25. (6) Xerosis (winter itch) rabiezahran@gawab.com 0124114646

  26. (9) Mycosis fungoides • rare form of T-cell lymphoma of the skin . • the disease is typically slowly progressive and chronic. • the skin becomes infiltrated with plaques and nodules that are composed of lymphocytes. rabiezahran@gawab.com 0124114646

  27. (10) Psoriasis chronic, relapsing, inflammatory skin disorder with a strong genetic basis. The plaque type of psoriasis is the most common, rabiezahran@gawab.com 0124114646

  28. The second step rabiezahran@gawab.com 0124114646

  29. The second step is to proceed to : * general history . *physical exam : # the review of systems and a search for : + Adenopathy , + Organomegaly . + Icterus . *A complete medication list is especially important, as medications must be ruled out as a possible cause of itching with or without a rash. rabiezahran@gawab.com 0124114646

  30. # Medications that provok itching by causing cholestasis : *phenothiazines (antipsychotic ) , *tolbutamide (oral anti-diabetic ) , *erythromycin, *estrogen , * progestin . *testosterone. rabiezahran@gawab.com 0124114646

  31. # Other drugs that can cause itching include: -morphine, -cocaine, -Butorphanol (Stadol) a morphinan-type synthetic opioid analgesic , -aspirin, -quinidine . -vitamin B complex. NB. :Even if the patient has been taking the medication for years it may still cause itch. rabiezahran@gawab.com 0124114646

  32. Note is itch is generalized or localized: *Itching of internal disease tends to be fairly generalized and not associated with primary lesions . Someexceptions exist, including the localized Anogenital itching of diabetes mellitus. rabiezahran@gawab.com 0124114646

  33. Note sequence of events : • * Itch precedes rash = suggestive of : • + systemic disorder. • + psychogenic pruritus. • Rash precedes itch = suggestive of cutanious disease. • Rash secondary to itching & scratching suggestive of : • + atopic dermatitis. • + some cases of psychogenic pruritus. rabiezahran@gawab.com 0124114646

  34. Note character of the sensation : * Itching = atopic dermatitis or other dermatological disease . * stinging, pricking burning = psychogenic pruritus rabiezahran@gawab.com 0124114646

  35. *Secondary changes from rubbing and scratching may be present. It is important not to mistake them for primary skin disease and make a mis-diagnosis of Aquagenic pruritus (itching provoked by bathing) may occur with : *xerosis . *polycythaemia vera . *Hodgkin’s disease. *mastocytosis . rabiezahran@gawab.com 0124114646

  36. third step rabiezahran@gawab.com 0124114646

  37. If no cause is identified after a thorough history and physical exam, the third step in evaluation includes a search for occult disease. rabiezahran@gawab.com 0124114646

  38. What Occult systemic disease which might cause Pruritus . rabiezahran@gawab.com 0124114646

  39. Five important systemic causes of itching (1) Hepatobiliary. (2) Renal. (3) Endocrine. (4) Haematological. (5) Malignancies. rabiezahran@gawab.com 0124114646

  40. 1-Hepato-biliary causes 1) Primary Biliary cirrhosis. 2) Biliary obstruction. 3)Cholestasis during pregnancy. rabiezahran@gawab.com 0124114646

  41. 1-Hepato-biliary: *The pathophysiologyof itch in hepatobiliarydisorders is not clear. *Attrib to bile salts in serum and tissues. *Endogenous opioidsmay play a causative role. *Itching may be the presenting complaint of drug-induced hepatic cholestasis (e.g. oral contraceptives) or malignancy that causes biliary obstruction. *There may be a predilection for the hands and feet. rabiezahran@gawab.com 0124114646

  42. 1-Hepato-biliary • pruritus may precede the development of jaundice by months, and is the presenting symptom in half of the patients. • Treatment : reverse cholestasis , liver transplant • Also helpful: • *oral guar gum (dietary fiber) • *binds bile acids; cholestyramine; • *rifampin! (inhibits bile uptake), • *opioid antagonists, codeine. • *ondansetron(zoferan)= serotonin receptor antagonist . • Not helpful: scratching rabiezahran@gawab.com 0124114646

  43. 2-Renal Chronic renal failure (even on dialysis) • Itching is rarely the presenting complaint in renal disease. • Often the diagnosis of renal insufficiency is established before itching develops. • Attributed to accumulation of : • histamine (mast cells), serotonin • Ca, Phos, Mg, Al, vit A also implicated. • Ultraviolet B phototherapy Inhibits histamine release & proliferation of dermal mast cells. • Antihistamines are not effective rabiezahran@gawab.com 0124114646

  44. 3-ENDOCRINE DISORDERS *Hyperthyroidism, *hypothyroidism, *diabetes mellitus. *carcinoid syndrome. All may be associated with pruritus. Both hyper- and hypothyroidism can present with itch. If hyperthyroidism is discovered, treating it results in clearance of itch, Use of emollients for dry skin in hypothyroidism leads to improvement. Localized anogenital pruritus occurs in diabetic patients and may be caused by mucocutaneouscandidiasis rabiezahran@gawab.com 0124114646

  45. 4-HAEMATOLOGICAL DISORDERS • (1) Polycythaemia vera often presents with aquagenic pruritus. • The itch begins after emerging from a bath or shower and lasts for 15–60 minutes. • No visible skin changes are present. • Pruritus results from increased histamine levels released from increased basophils and mast cells. • Patients with aquagenicpruritus should be followed periodically for development of polycythaemia vera because the symptoms may precede diagnosis by months. • Pruritus and iron deficiency may occur in patients with polycythaemia vera & correction of the iron deficiency may result in improvement. rabiezahran@gawab.com 0124114646

  46. HAEMATOLOGICAL DISORDERS (2) Other Myeloproliferative disorders (leukaemia,monoclonalgammopathy & multiple myeloma Lymphoma ) (3) iron deficiency anemia that is unassociated with polycythaemia vera, may be associated with pruritus rabiezahran@gawab.com 0124114646

  47. 5-MALIGNANT NEOPLASMS The association of malignancy and generalized itching is quite rare of all malignancies : 1: Hodgkin’s disease : more frequently presents with Pruritus, which may precede the diagnosis by months. The severe& often burning itch of Hodgkin’s disease responds only to treatment of the underlying lymphoma. rabiezahran@gawab.com 0124114646

  48. MALIGNANT NEOPLASMS 2: Cutanious T-cell lymphoma :(e.g. mycosis fungoides ). 3:Visceral cancers : -adenocarcinoma. -squamous cell cancers of various organs. 3: CNS . tumors . 4: multiple myeloma. rabiezahran@gawab.com 0124114646

  49. INFECTION Patients with infectious diseases, most notably: * parasitic. *HIV infection, can present with pruritus without easily recognized primary skin lesions. The itch of HIV may be secondary to co-morbid conditions such as: *scabies, *seborrhoea. *candidiasis. *folliculitis . *lymphoma. but it may also result from the direct effects of the virus. rabiezahran@gawab.com 0124114646

  50. PSYCHOGENIC ITCHING *Psychogenic pruritus is diagnosed by exclusion. *It is especially important to consider and exclude scabies and pediculosis . *Some patients may have delusions of parasitosis or neurotic excoriations. *These patients complain of the sensation of insects crawling across or emerging from the skin. *Delusions of parasitosis may respond to pimozide(Antipsychotic). rabiezahran@gawab.com 0124114646