身上发痒是怎么回事
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ETIOLOGIES OF ITCH
# Key points
The common nondermatologic causes of itch include renal,hepatobiliary,oncologic,neuropathic,and psychogeneic etiologies.
The risk factors that suggest that itch is associated with an underlying malignancy include itch with a duration of less than 12 months,age greater than 60 years,male sex,and history of liver disease and tobacco use.
HIV-positive patients are at increased risk of experiencing pruritic dermatoses,such as lichen simplex chronicus,prurigo nodularis,and scabies.
Various inflammatory,neoplastic,genetic,infestation or infectious,and autoimmune dermatologic diseases can cause itch ). Approximately 50% of patients with primary diagnoses of dermatologic problems reported pruritus,with 25% reporting severe itch. Itch is also a common symptom associated with numerous nondermatologic conditions and may arise in the context of various systemic,neuropathic,and psychogenic etiologies ).
[](https://ncbi.nlm.nih.gov/pmc/articles/PMC8678917/figure/F1/)
[Open in a separate window](https://ncbi.nlm.nih.gov/pmc/articles/PMC8678917/figure/F1/?report=objectonly) [Fig 1.](https://ncbi.nlm.nih.gov/pmc/articles/PMC8678917/figure/F1/)
Itch can arise in the context of various systemic,neuropathic,and psychogenic etiologies.
# Table I.
Examples of dermatologic causes of itch
Types
Examples
Inflammatory
Atopic dermatitis,contact dermatitis,psoriasis,lichen planus,urticaria,pityriasis rubra pilaris,prurigo nodularis,dermal hypersensitivity reaction,Grover disease,granuloma annulare,and primary cutaneous amyloidosis
Infections or infestations
Bacterial,viral,fungal,and parasitic infections (eg,scabies and shistosomal dermatitis)
Neoplastic
Cutaneous T-cell lymphoma and nonmelanoma skin cancer
Autoimmune
Bullous pemphigoid,dermatitis herpetiformis,dermatomyositis,and cutaneous lupus erythematosus
Genetic
Darier disease,Hailey-Hailey disease,epidermolysis bullosa pruriginosa,Sj?gren-Larsson syndrome,and porphyria cutanea tarda
Fibrosis-related
Scar-related pruritus,keloids,and sarcoidosis
[Open in a separate window](https://ncbi.nlm.nih.gov/pmc/articles/PMC8678917/table/T1/?report=objectonly)
# Systemic causes of itch
Renal.
Itch is a common manifestation of advanced chronic kidney disease,with 40%−90% of hemodialysis patients experiencing chronic pruritus. – The itch with chronic kidney disease is related to uremic neuropathy,systemic inflammation,and increased μ-opioid receptor activity along with decreased κ-opioid activity. Secondary hyperparathyroidism due to chronic kidney disease has also been postulated as a cause of generalized pruritus with an unclear mechanism,suggested by small cohort studies that observed improvement of itch following parathyroidectomy. –
Hepatobiliary.
Cholestasis from conditions affecting the hepatobiliary system is a common culprit of itch. These include both primary and secondary causes of biliary obstruction that lead to a systemic accumulation of bile acid,including primary biliary cholangitis,primary sclerosing cholangitis,intrahepatic cholestasis of pregnancy,viral hepatitis,and cirrhosis. – Cholestatic itch arises from a complex interplay between bile acids,lysophosphatidic acid,bilirubin,and increased μ-opioid receptor activity. Recent studies have suggested that bilirubin induces pruritus through the activation of Mas-related G-protein coupled receptor member X4 receptors on sensory neurons. Cholestatic pruritus can be uniquely characterized by the presence of itch that initially affects the palms and soles,becoming more generalized with disease progression.
Endocrine.
Pruritus is more prevalent in diabetic patients than in healthy controls (26.3% vs 14.6%,respectively). Patients with diabetes are predisposed to conditions associated with itch,including superficial mycotic infections,neuropathy,excoriation disorder,and pruritus of the scalp and vulva. – Itch in diabetes may be secondary to the detrimental effect of increased glucose on cutaneous nerve fibers,representing a sequela of diabetic polyneuropathy. Uncontrolled hyperthyroidism causes itch in a subset of patients,possibly due to reduced itch threshold due to increased body temperature,vasodilation,and kinin activation.,Hypothyroidism is less frequently associated with itch,but it is associated with xerosis.
Rheumatologic.
Itch is a common symptom of various rheumatologic diseases,due to downstream effects of variable immune activation. Pruritus occurs in approximately half of patients with systemic sclerosis who often have accompanying xerosis. Itch is also a common symptom of dermatomyositis,with 50.8% of patients with dermatomyositis reporting moderate-to-severe itch and itch severity correlating with the degree of skin involvement. The other autoimmune diseases featuring varying degrees of itch include Sj?gren syndrome and both cutaneous and systemic lupus erythematosus., Hematologic or oncologic.
Itch can be a prodrome of malignancy,often preceding other signs and symptoms. Although the exact pathophysiology is not known,malignancy-related pruritus may result from a local inflammatory reaction to the tumor or as a paraneoplastic phenomenon. Itch is particularly common in hematologic malignancies,with prevalence estimates as high as 30% among patients with Hodgkin lymphoma,15% among patients with non-Hodgkin lymphoma,and 67% among patients with polycythemia vera.,Patients with polycythemia vera often present with aquagenic pruritus,evoked by contact with water of any temperature.,Other hematologic conditions can also present with generalized pruritus,with eczematous,urticarial,or lichenified skin findings,including hypereosinophilic syndrome,defined as 2 or more separate examinations of absolute eosinophil count >1.5 ? 109/L in the peripheral blood in the course of 1 month.,Itch is also associated with cutaneous lymphomas and other dermatologic cancers. – Among solid tumors,there is a significant association between itch and cancers of the hepatobiliary system. Although pruritus is thought to be an uncommon symptom in other solid malignancies,there have been case reports of itch occurring in patients with non-small–cell lung carcinoma,insulinoma,gastric carcinoid tumors,and other solid malignancies.,A longitudinal Danish study demonstrated that rates of both hematologic and various solid cancers were higher than expected in patients with pruritus. The incidence ratio of cancers was the most increased compared to the general population within the first 3 months of pruritus diagnosis and remained elevated during the first 12 months. Another study has also suggested that patients with chronic itch but without primary dermatologic findings are at increased risk of an underlying malignancy. This increased risk was especially associated with age older than 60 years,male sex,and history of liver disease and tobacco use. Racial differences have been observed in the association between itch and certain malignancies. Notably,Black pruritic patients may have greater odds of hematologic malignancies,whereas White pruritic patients may be at increased risk of liver and skin malignancies.
Other systemic etiologies.
Itch can occur as an iatrogenic adverse effect of many drugs,suggesting that it is important that physicians across specialties remain vigilant. The common culprits of drug-induced pruritus include immune checkpoint inhibitors,; agents targeting epidermal growth factor receptor,B-Raf proto-oncogene,cytotoxic T-lymphocyte-associated protein 4,and programmed cell death protein 1/ programmed cell death-ligand 1 – ; opioids; and chloroquine and other antimalarials.
Although their exact pathophysiology is yet to be explored,the other potential etiologies of itch may include iron-deficiency anemia,exposure to heavy metal,vitamin deficiency,HIV,and other viral infections. One study found that 13.6% of men and 7.4% of women with iron-deficiency anemia presented with itching,which was significantly increased compared with controls. Elevated blood levels of heavy metals,including cadmium and lead,are also associated with chronic itch. Low levels of vitamin D were observed in patients with chronic pruritic skin conditions,including atopic dermatitis,psoriasis,and chronic urticaria,– whereas low levels of vitamin B12 were noted in patients with generalized itch from various systemic causes. Oral or topical vitamin supplements had modest positive effects in reducing pruritus in limited studies,although definitive studies are lacking on the association of vitamin deficiencies with the development of chronic itch. –
Itch is also commonly reported in patients with viral infections,particularly among those with HIV. Pruritus is a significant cause of comorbidity among HIV-positive patients,of whom 13%−45% experience chronic itch.,Many HIV-positive patients have concomitant pruritic disorders,including lichen simplex chronicus,prurigo nodularis,scabies,seborrheic dermatitis,mycosis fungoides,and psoriasis.,– Patients with advanced HIV are also at risk for eosinophilic folliculitis,an intensely pruritic eruption of follicular papules and pustules in the setting of elevated eosinophils.,# Neuropathic causes of itch
Itch can arise from neural dysregulation,either from excess stimulation of the peripheral sensory nerves or from the loss of the central inhibition of the itch pathway. Neuropathic pruritus is estimated to comprise 8% of all cases of chronic pruritus. Commonly recognized causes of neuropathic itch often have distinct dermatomal localizations ),but can become generalized.
[](https://ncbi.nlm.nih.gov/pmc/articles/PMC8678917/figure/F2/)
[Open in a separate window](https://ncbi.nlm.nih.gov/pmc/articles/PMC8678917/figure/F2/?report=objectonly) [Fig 2.](https://ncbi.nlm.nih.gov/pmc/articles/PMC8678917/figure/F2/)
Neuropathic etiologies of itch. C,Cervical; L,Lumbar; T,Thoracic.
Brachioradial pruritus most commonly affects middle-aged women of lighter skin types and worsens with exposure to sunlight.,It typically presents initially with localized itch or a tingling or burning sensation along either proximal upper extremities and shoulders along the C3-C7 dermatomes,often with accompanying degenerative changes noted in the respective cervical spine.,– Brachioradial pruritus can become generalized,in a phenomena related to central neural sensitization.
Notalgia paresthetica presents with localized,unilateral pruritus of the area medial to the scapula on the mid-to-upper back. It originates from nerve entrapment of spinal nerves that arise from T2 to T6. Itch localization often correlates with radiologic findings of the vertebrae,as well as with reduced intraepidermal nerve fiber density in the skin likely as a results of chronic scratching.
Scalp dysesthesia presents with an uncomfortable sensation of the scalp. Although the healthy scalp normally has decreased sensitivity of C-fibers to itch,scalp dysesthesia can result from degenerative changes at C2-C7 levels.,Similarly,anogenital pruritus is associated with degenerative changes of the lower spine at L4-S2 levels.
The other neurologic conditions associated with itch include trigeminal trophic syndrome,cerebrovascular events,brain infections (eg,encephalitis,Creutzfeldt-Jakob disease),and small fiber neuropathies.
# Psychogenic causes of itch
Itch is commonly reported among patients with anxiety and depression,although the pathophysiology still needs further investigation. Itch severity correlates with the level of depressive symptoms. Because of its detrimental effects on sleep and quality of life,chronic pruritus leads to increased psychiatric burden of disease and higher odds of suicidal ideation. Itch also is often reported in patients with primary psychodermatologic conditions,including somatic symptom disorder,dermatitis artefacta,obsessive-compulsive disorder,delusional infestation,excoriation disorder,and Morgellons disease. Excoriation disorder is associated with type 2 diabetes mellitus,anxiety,and depression. Chronic itch can be a manifestation of an underlying substance use disorder,including opioids,cocaine,and methylenedioxymethamphetamine.","department":"
