Itching (Pruritus): Causes

Pathogenesis (development of disease)

Many different causes of pruritus can be distinguished. 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 area of the corium (dermis) and epidermis (epidermis), which is interpreted in the central nervous system as itching. Activation of the nerve terminals 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. No valid studies are available on the pathogenesis of uremic pruritus (renal or nephrogenic pruritus/renal pruritus). It is likely that uremic pruritus is part of the large spectrum of metabolic-uremic or neuropathic-uremic changes. Pruriginous (“itch-inducing”) substances are thought to be responsible for the pathogenesis of hepatic pruritus (liver-related itching). The following substances are discussed: Histamine, bile salts, endogenous opioids, and steroid metabolites. Autotaxin and lysophosphatidic acid have been identified as potential pruritogens (“itch-producing substances”) in cholestasis (biliary stasis). In old age, systemic or multifactorial triggers mostly occur; dermatoses, on the other hand, which form the main part in under-65-year-olds with about 40%, are only about 20% in the elderly.

Etiology (Causes)

Biographic causes

Behavioral causes

Disease-related causes

Respiratory system (J00-J99)

  • Allergic rhinitis (hay fever).

Blood, blood-forming organs – immune system (D50-D90).

Endocrine, nutritional and metabolic diseases (E00-E90).

  • Iron deficiency
  • Diabetes insipidus – hormone deficiency-related disorder in hydrogen metabolism, resulting in extremely high urine excretion (polyuria; 5-25 l/day) due to impaired concentration capacity of the kidneys.
  • Diabetes mellitus type 2
  • Fructose intolerance (fruit sugar intolerance)
  • Hemochromatosis (iron storage disease)
  • Hyperparathyroidism – excessive production and secretion of parathyroid hormone, triggered by an adenoma or hyperplasia of one or more parathyroid glands (epithelial corpuscles); this leads to increased bone resorption and thus to an increased calcium concentration in the blood
  • Hyperthyroidism (hyperthyroidism).
  • Hyperuricemia (increase in uric acid levels in the blood).
  • Hypothyroidism underactive thyroid gland
  • Lactose intolerance (milk sugar intolerance)
  • Malnutrition
  • Thyroid dysfunction (hypo- or hyperthyroidism / hypothyroidism or hyperthyroidism).
  • Vitamin A deficiency
  • Vitamin D deficiency

Skin and subcutaneous tissue (L00-L99)

  • Allergic contact dermatitis (contact allergy) – skin inflammation resulting from an allergic reaction.
  • Aquagenic pruritus (AP) – area-occurring prickly itching with varying severity in close connection with the moistening of affected skin areas by water (after showers or full baths); decrease in symptoms without therapy after a few minutes to about 2 hours; distinction between a primary (= idiopathic) and a secondary AP; the most common cause is polycythaemia vera (PV). Furthermore, occurrence in other myeloproliferative neoplasms and, less frequently, in other systemic, especially hemato-oncological diseases (see below “Neoplasms – Tumor Diseases“). In addition, cases of iatrogenic AP have been described after ingestion of bupropion, clomipramine, or hydroxychloroquine.
  • Drug-induced exanthema
  • Atopic eczema (neurodermatitis)
  • Dermatitis herpetiformis (synonyms: Duhring’s disease, Duhring-Brocq disease) – skin disease from the group of blistering autoimmune dermatoses with subepidermal blistering.
  • Herpes gestationes (pemphigoid gestationes) – skin disease in pregnancy.
  • Lichen sclerosus – rare, chronic inflammatory, progressive connective tissue disease of the skin.
  • Bullous pemphigoid – most common autoimmune disease of old age.
  • Eczema – contact eczema, the exsiccation eczema (also called eczema of old age, or eczéma craquelé).
  • Lichen ruber planus (nodular lichen).
  • Lichen sclerosus et atrophicans (genital)
  • Lichen simplex
  • Miliaria rubra (synonyms: Dermatitis hidrotica, Friesel, Hidroa, heat pimples, heat flares, sweat frizzles, sweat vesicles, sweat blisters, red dog) – usually itchy rash (Miliaria rubra = itchy reddish papules, vesicles or papulovesicles) caused by increased sweating in hot weather.
  • Paraneoplastic pruritus, due toe.g. lymphoma, esp. Hodgkin’s disease, polycythaemia vera; symptoms: generalized itching, possibly aquagen (“water-related”; aquagenic pruritus) or with alcohol consumption.
  • Pityriasis rosea (rose lichen).
  • Prurigo simplex acuta – disease with episodic, disseminated, itchy papules; mainly children affected.
  • Pruritus sine materia: pruritus without apparent cause.
  • Psoriasis (rare; especially in psoriasis inversa or psoriasis guttata).
  • Stasis dermatitis (eczema venosum) – therapy-resistant chronic dermatitis (inflammatory reaction of the skin) of the lower legs in chronic venous insufficiency (CVI; chronic venous insufficiency); is accompanied by the clinical symptom triad redness, scaling and excoriations (superficial substance defect with exposure of the papillary bodies and punctate blood leaks, scarring possible); the type of eczema varies from neurodermatitis-like areal affection to nummular (coin-shaped skin change)-microbial type; in the nummular-microbial type, the hyperpigmented eczema foci are not infrequently located above the visible varicose veins (varicose veins)
  • Urticaria (hives)
  • Xeroderma (dry skin)

Cardiovascular system (I00-I99)

  • Apoplexy (stroke)

Infectious and parasitic diseases (A00-B99).

  • Bacterial infections, unspecified
  • Chronic viral infections (here: HBV/HCV/HIV/HSV infection).
  • Exanthematic viral diseases (e.g. chickenpox).
  • Helicobacter pylori infection
  • Hepatitis C (virus type C liver inflammation).
  • Herpes zoster (shingles)
  • HIV infection (due todry skin)
  • Mycoses (fungal diseases)
  • Parasitoses (parasite infestation)
  • Scabies (scabies)
  • VZV reactivation – reactivation of the varicella zoster virus (VZV).

Liver, gallbladder, and biliary tract – Pancreas (pancreas) (K70-K77; K80-K87).

  • Cholestasis (biliary stasis) – cholestatic pruritus; in liver disease (e.g., primary biliary cholangitis (PBC; synonyms: nonpurulent destructive cholangitis; formerly primary biliary cirrhosis)/bile duct inflammation, hepatitis B-/-C infection) – hepatic pruritus:
    • Circadian rhythm, strongest intensity in the evening and at night; localization on the extremities, esp. on the palms of the hands and soles of the feet; pruritus may also be generalized
    • Women: Increase in pruritus premenstrual, by hormone replacement therapy (HRT) and at the end of pregnancy.

Mouth, esophagus (esophagus), stomach, and intestines (K00-K67; K90-K93).

  • Malassimilation syndromes (maldigestion/food can no longer be broken down into its absorbable components or can only be broken down inadequately, malabsorption/lack of absorption (absorption) of substrates from the already predigested food pulp).
  • Food allergy
  • Digestive disorders, unspecified
  • Celiac disease (gluten-induced enteropathy) – disease of the mucosa of the small intestine (small intestinal mucosa) due to hypersensitivity to the cereal protein gluten.

Musculoskeletal system and connective tissue (M00-M99).

Neoplasms – tumor diseases (C00-D48) [pruritus may precede diagnosis by years].

  • Essential thrombocythemia (ET) – neoplasia belonging to the myeloproliferative neoplasia (MPN) form group/group of malignancies of the hematopoietic system → aquagenic pruritus.
  • Brain tumors – pruritus of the nostrils.
  • Hypereosinophilia syndromes – heterogeneous group of diseases defined as marked and persistent eosinophilia (increased presence of eosinophilic granulocytes/white blood cells) of peripheral blood of more than 1.5 x 109/L and evidence of eosinophilic organ damage for more than 6 consecutive months
  • Juvenile xanthogranuloma (JXG) – benign form of histiocytosis occurring in infancy and early childhood (heterogeneous group of rare diseases with tumor-like lesions characterized by proliferation (abnormally high number) of histiocytic cells).
  • Carcinoid tumor (synonyms: Carcinoid syndrome, neuroendocrine tumors, NET) – tumors originating from the neuroendocrine system; they are located predominantly in the appendix/appendix appendix (appendiceal carcinoid) or in the bronchi (bronchial carcinoid); other localizations include the thymus (thymic carcinoid), ileum/ruminal intestine (ileal carcinoid), rectum/foregut (rectal carcinoid), duodenum/duodenal intestine (duodenal carcinoid), and stomach (gastric carcinoid); typical symptoms are characterized by the triad of diarrhea (diarrhea), flushing (facial flushing), and Hedinger syndrome (endocardial fibrosis of the right heart, which can lead to tricuspid regurgitation (leakage with backflow of blood from the heart valve between the right atrium and the right ventricle) and pulmonary stenosis (narrowing in the outflow tract from the right ventricle to the pulmonary artery).
  • Cutaneous D-cell lymphoma (erythrodermic mycosis fungoides, Sézary syndrome).
  • Leukemias (blood cancers) – e.g. chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL).
  • Lymphomas (tumors of the lymphatic system) – Hodgkin’s disease, non-Hodgkin’s lymphoma (esp. T-cell non-Hodgkin’s lymphoma).
  • Mastocytosis – two main forms: cutaneous mastocytosis (skin mastocytosis) and systemic mastocytosis (whole body mastocytosis); clinical picture of cutaneous mastocytosis: Yellowish-brown spots of varying size (urticaria pigmentosa); in systemic mastocytosis, there are also episodic gastrointestinal complaints (gastrointestinal complaints), (nausea (nausea), burning abdominal pain and diarrhea (diarrhea)), ulcer disease, and gastrointestinal bleeding (gastrointestinal bleeding) and malabsorption (disorder of food absorption); In systemic mastocytosis, there is an accumulation of mast cells (cell type that is involved in, among other things, allergic reactions). Among other things, involved in allergic reactions) in the bone marrow, where they are formed, as well as accumulation in the skin, bones, liver, spleen and gastrointestinal tract (GIT; gastrointestinal tract); mastocytosis is not curable; course usually benign (benign) and life expectancy normal; extremely rare degeneration mast cells (= mast cell leukemia (blood cancer)).
  • Myelodysplastic syndrome (MDS) – group of heterogeneous (inconsistent) diseases of the bone marrow (stem cell diseases).
  • Paraneoplastic syndrome – non-metastatic symptoms based on humoral remote effect abdominal tumor disease, which may subside after tumor removal.
  • Polycythaemia vera – abnormal proliferation of blood cells (particularly affected are: especially erythrocytes/red blood cells, to a lesser extent also platelets (thrombocytes) and leukocytes/white blood cells); prickly itching after contact with water (aquagenic pruritus) or during temperature fluctuations.

Psyche – nervous system (F00-F99; G00-G99).

  • Anorexia nervosa (anorexia nervosa)
  • Depression
  • Dermatozoa delusion – delusional belief that living things are under the skin.
  • Multiple sclerosis (MS)
  • Polyneuropathy – disease of the nerves of the peripheral nervous system; depending on the cause, motor, sensory or autonomic nerves may be affected; sensitivity disorders.
  • Postzosterneuralgie (PZN) – extremely severe nerve pain (neuralgia) as a result of shingles (herpes zoster).
  • Tabes dorsalis (Neurolues) – late stage of syphilis, in which there is demyelination of the spinal cord.

Symptoms and abnormal clinical and laboratory findings not elsewhere classified (R00-R99).

  • Icterus (jaundice)

Genitourinary system (kidneys, urinary tract – reproductive organs) (N00-N99).

  • Kraurosis vulvae (vulvar dystrophy) – Pruritus vulvae (itching of the external female genital organs).
  • Renal insufficiency (kidney failure), chronic – renal (kidney-related) pruritus.
  • Uremia / dialysis patients (occurrence of urinary substances in the blood above normal values; urine poisoning) – uremic pruritus (synonym: nephrogenic pruritus); often generalized; felt most strongly on the legs (20-50% of these patients).

Injuries, poisonings, and certain other sequelae of external causes (S00-T98).

  • Insect bites
  • Food allergy
  • Pseudoallergies (eg due toexcipients in medicines).

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

  • Iron deficiency

Medication

Environmental pollution – intoxications (poisonings).

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