Pruritus Senilis: Causes

Pathogenesis (development of disease)

The most common cause of generalized pruritus senilis is dehydration of the skin. In older age, due to the reduction of lipid production (sebostasis) in the stratus corneum (horny cell layer), xeroderma (xerosis cuti: “dry skin“) results in chronic pruritus (pruritus senilis; most common cause of pruritus in old age). The loss of lipids leads to a reduced water-binding capacity, with the result that the horny layer tears. Inflammatory cells can thus migrate into the skin and contribute to the development of pruritus. The use of certain medications (see below) can also cause or aggravate dry skin. The pathomechanism for pruritus lies in the activation of free nerve endings of polymodal C-nerve fibers in the corium (dermis) and epidermis (epidermis), which is interpreted as itching in the central nervous system. Activation of the nerve endings occurs through contact with mediators (including histamine (from mast cells), serotonin, prostaglandins, kinins) released by inflammatory changes in the skin (e.g., infections) or increased opioidergic tone.

Etiology (Causes)

Biographic causes

• Age – > 60 years
• Hormonal factors – climacteric (menopause in women), andropause (menopause in men).

Behavioral causes

• Nutrition
  • Malnutrition
  • Spices (e.g. chili)
• Drug use
  • Cocaine
  • Opiates or opioids (alfentanil, apomorphine, buprenorphine, codeine, dihydrocodeine, fentanyl, hydromorphone, loperamide, morphine, methadone, nalbuphine, naloxone, naltrexone, oxycodone, pentazocine, pethidine, piritramide, remifentanil, sufentanil, tapentadol, tilidine, tramadol)
• Psycho-social situation
  • Psychosomatic stress
  • Stress
• Washing behavior – excessive use of:
  • Soaps or shower products
  • Bath additives
  • Brushing or rubbing the skin (→ in older people, this washes off the already thinner sebaceous film of the skin – the skin loses even more moisture)
• Use of alcohol-containing cleansing agents
• Contact with fabrics (esp. wool)

Causes due to disease

• Aquagenic pruritus of the elderly (APE=Aquagenic pruritus of the elderly) – itching that occurs in temporal relation to the wetting of affected skin sites by water Note: differential diagnosis polycythaemia vera.

Laboratory diagnoses – laboratory parameters that are considered independent risk factors.

• Iron deficiency

Medication

• Α4β7-integrin antagonist (vedolizumab).
• ACE inhibitors (benazepril, captopril, cilazapril, enalapril, fosinopril, lisinopril, moexipril, peridopril, quinapril, ramipril, spirapril).
• Allopurinol
• Analgesics
  • NSAID (nonsteroidal anti-inflammatory drug (NSAID); also nonsteroidal anti-inflammatory drug (NSAP) or NSAID, non steroidal anti- inflammatory drugs) – acetylsalicylic acid (ASA; 1-5% of those exposed).
  • Paracetamol
• Angiogenesis inhibitors (sorafenib, sunitinib).
• Antiarrhythmics (amiodarone, quinidine).
• Antibiotics
  • Aminopenicillins (amoxicillin); esp. as amoxicillin/clavulanic acid combination (frequency: very low).
  • Β-Lactam antibiotics (aminopenicillins) – ampicillin.
  • Beomycin (> 5% of those exposed).
  • Macrolide antibiotics (erythromycin).
  • Nitroimidazoles (metronidazole)
  • Sulfonamides
  • Tetracyclines (minocycline)
  • Trimethoprim and sulfamethoxazole
• Antidepressants
• Antiepileptic drugs
  • Aromatic anticonvulsants (carbamazepine, lamotrigine, phenobarbital).
  • Functionalized amino acid (lacosamide).
  • Phenytoin
  • Selective dopamine and norepinephrine (marginally also serotonin) reuptake inhibitor (NDRI) – bupropion [aquagenic pruritus].
  • Valproic acid/valproate
• Antihypotensives: α-adrenoceptor agonist (midodrine).
• Antimalarials (artesunate, chloroquine, primaquine) [aquagenic pruritus].
• Antifungal agents, local
  • Imidazole derivatives (clotrimazole, econazole, ketoconazole, miconazole).
  • Morpholine (amorolfine)
• Antipsychotics (neuroleptics) – chlorpromazine, phenothiazines.
• Antirheumatic drugs
  • NSAID (nonsteroidal anti-inflammatory drug (NSAID); also nonsteroidal anti-inflammatory drug (NSAP) or NSAID, non steroidal anti- inflammatory drug) – acetylsalicylic acid (ASA; 1-5% of those exposed).
• Antisympathotonic drug (clonidine).
• Arsenic trioxide
• Α2-agonists (apraclonidine, brimonidine, clonidine).
• Beta-blockers
  • Non-selective beta-blockers (e.g., carvedilol, propranolol, soltalol).
  • Selective beta-blockers (e.g., atenolol, bisoprolol, metoprolol).
• Biologicals (etanercept, infliximab, secukinumab, ustekinumab).
• Intestinal therapeutics, anti-inflammatory (mesalazine).
• Dicarboxylic acid
• Direct Factor Xa inhibitor (rivaroxaban).
• Fibrate (Clofibrate)
• Gold preparations (gold salts)
• Glutamate modulator (acamprosate)
• Hormones
  • Anabolic steroids
  • Glucocorticoids (betamethasone dipropionate, mometasone furoate, clobetasol).
  • Estrogens (ethinyl estradiol, estradiol).
  • Prostaglandin (alprostadil)
  • Selective estrogen receptor modulator (SERM) – tamoxifen
  • Testosterone
• Hydroxyethyl starch (pruritus often persists for months after infusion) [median latency between hydroxyethyl starch administration and onset of pruritus is 3 weeks].
• Hypnotics/sedatives (clomethiazole).
• Intestinal anti-inflammatory (sulfasalcin).
• Insecticides and acaricides
  • Pyrethroids (allethrin, permethrin)
  • Pyrethrins (pyrethrum)
• Colloids (colloidal solution)
• Lithium
• Monoclonal antibodies
  • Anti-CD25 antibody daclizumab (DAC).
  • IgG1 antibody pertuzumab
  • PD-1 immune checkpoint inhibitors: Nivolumab
  • Trastuzumab
• Mucolytics (acetylcysteine (ACC); N-acetylcysteine (NAC); N-acetyl-L-cysteine).
• Narcotics (halothane)
• Nicotinic acid derivatives (nicotinic acid)
• Norepinephrine reuptake inhibitor (atomoxetine).
• Opiates or opioids (alfentanil, apomorphine, buprenorphine, codeine, dihydrocodeine, fentanyl, hydromorphone, loperamide, morphine, methadone, nalbuphine, naloxone, naltrexone, oxycodone, pentazocine, pethidine, piritramide, remifentanil, sufentanil, tapentadol, tilidine, tramadol).
• Peroxides (benzoyl peroxide).
• Phytotherapeutics (horse chestnut (triterpene glycoside).
• Proton pump inhibitors (proton pump inhibitors, PPI; acid blockers) – esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole.
• Quaternary amonium compounds (dequalinium.
• Retinoids (alitretinoin, tazarotene)
• X-ray contrast media (as an immediate reaction).
• Statins – lovastatin, simvastatin
• Sulfasalazine (INN), also salazosulfapyridine.
• Topical calcineurin inhibitors (pimecrolimus, tacrolimus).
• Tuberculostat (isoniazid).
• Vasodilators (diazoxide)
• Antivirals (aciclovir, brivudine, famciclovir, simeprevir, valaciclovir).
  • Non-nucleoside reverse transcriptase inhibitors (NNRTIs) – efavirenz, nevirapine, rilpivirine.
  • NS5A inhibitors (daclatasvir, ledipasvir, ombitasvir).
  • Protease inhibitors (PI; protease inhibitors) – boceprevir, paritaprevir, telaprevir (anal pruritus).
• Cytostatic drugs (busulfan, ingenol mebutate, methotrexate (MTX), sunitinib, temodal).
• See also under “Photosensitizing drugs“.

Environmental pollution – intoxications (poisonings).

• Irritants (chemicals, solvents)
• Air conditioning (dry air)
• Overheated rooms
• Dry room climate
• Sun (frequent sunbathing)
• Winter – cold-dry climates; dry heating air (→ reduction of sebaceous gland secretion).