Urticaria pigmentosa Q82.2

Urticaria pigmentosa is by far the most common type of cutaneous mastocytosis. The early childhood forms of cutaneous mastocytosis usually correspond to the clinical picture of solitary or multiple mastocytoma.

Urticaria pigmentosa is a clonal disease of the CD34+ hematopoietic stem cell in the bone marrow with development of clinically distinct clinical pictures, which are characterized by mast cell accumulation in the skin (and possibly also in internal organs - especially bone marrow, lymphatic organs).

• In cutaneous mastocytosis of the urticaria pigmentosa type, the proliferation of mast cells is essentially limited to the skin.
• Systemic mastocytosis can occur with or without skin changes (skin changes generally correspond to the clinical picture of Urticaria pigmentosa). Systemic mastocytosis usually begins in adulthood. The clinical sympotaxis is heterogeneous and depends on the mast cell load. Anaphylactic reactions and other reactions triggered by mast cell mediators such as flush symptoms, pruritus, urticaria, asthma attacks, abdominal complaints such as diarrhoea or gastrointestinal ulcers, as well as joint and bone pain characterize the clinical picture.

Urticaria pigmentosa (overview) = disseminated mastocytosis; 5 mastocytomas = Urticaria pigmentosa

• Urticaria pigmentosa of the adult (cutaneous mastocytosis)
  • Maculo-papular cutaneous mastocytosis (Urticaria pigmentosa - classic type)
  • Teleangiectasia macularis eruptiva perstans
• Urticaria pigmentosa of childhood
  • Urticaria pigmentosa (classic type)
  • Teleangiectasia macularis eruptiva perstans (extremely rare in childhood)

No gender preference. In childhood the incidence of cutaneous mastocytosis is 1:150,000 per year

Most adult patients show an activating point mutation of the KIT gene (KIT D816V). Both the expression of KIT (CD117) on the cell surface and the mutation are not specific for mastocytosis - see below mastocytosis (overview).

The juvenile Urticaria pigmentosa does not show the activating c-kit mutation.

In childhood urticaria pigmentosa, the first manifestation often occurs in the first 24 months of life, less frequently thereafter.

In the adult form (adult urticaria pigmentosa) the peak of manifestation is found in middle adulthood (40-60 years).

Ubiquitous; mainly on the trunk and upper and lower extremities; rarely on the face, palms of the hands and soles of the feet. Very rarely mucosal involvement.

Flat, oval or round, grey-brownish or reddish-brownish spots, 0,1-0,5 cm in size. The clinical symptoms of the patients are due to the release of the various mast cell mediators (mediator symptomatology). In addition to histamine, tryptase, heparin, leukotrienes, prostaglandins and various cytokines such as TNF-alpha, interleukins. After firmly coating the lesions, there is a urticarial reaction in the foci(Darian sign); more rarely subepidermal blistering. Frequently an eleviated dermographism can also be induced. Initially weak, later stronger lesional pigmentation. The most frequent concomitant symptom is itching, whereby interleukin-31 is attributed a special pathogenetic significance (Wagner N et al. 2018)

Regarding the clinical course, juvenile and adult formers behave differently.

Special forms:

• Urticaria pigmentosa haemorrhagica
• exanthematic urticaria pigmentosa
• Urticaria pigmentosa bullosa
• Urticaria pigmentosa xanthelasmoidea
• Teleangiectasia macularis eruptiva perstans.

In case of systemic mastocytosis, tryptase is determined according to the guidelines (standard value: <20µg/l). If the value is exceeded, systemic mastocytosis is considered possible and a bone marrow biopsy and screening for further system involvement is sought. If the values are low, extensive diagnostic procedures are usually not necessary without compelling clinical indications. In a larger study, systemic mastocytosis was confirmed in 32% of patients with cutaneous mastocytosis in bone marrow histology. The mean tryptase value of the collective with system involvement was 43.9±39.93µg/l (3.74-173µg/l), without system involvement 19.63±13.31 µg/l (2.44-54 µg/l).tryptase increases > 20µg/l were detectable in 43% of patients with pure cutaneous mastocytosis. 28% of patients with systemic mastocytosis showed normal values. Thus the laboratory value "tryptase" does not seem to be a reliable parameter for the question of systemic involvement.

In addition, the determination of N-methylhistamine or 1,4-methylimidazole acetic acid in the collective urine can be performed.

Often not very spectacular histological image in HE-stained specimen. Discrete hyperpigmentation of the otherwise unchanged epidermis. Shattered, perivascularly accentuated round cell infiltrates in the reticular dermis. The mast cell-rich quality of the infiltrate (Giemsa staining; CD117; CD25) is only recognizable with histochemical or immunohistochemical imaging.

Symptomatic, s.a. mastocytosis diffuse of the skin.

• Patient education about the character of the disease and provoking factors. Avoidance of triggering drugs such as non-steroidal anti-inflammatory drugs, acetylsalicylic acid, codeine, procaine, polymyxin B, muscle relaxants, X-ray contrast media. No mechanical irritation such as friction (dry rubbing) or sudden temperature changes (jumping into cold water). Avoid insect bites. Caution! Triggering by i.v. applied, short-term effective narcotics is possible!
• Diet: A diet low in histamine and possibly also low in salicylate is recommended, see below Urticaria, chronic. Histamine liberators should be avoided.

• Antihistamines: Combinations of a non-sedative H ₁ antagonist such as levocetirizine (Xusal) once/day 5 mg p.o. or a sedative H ₁ antagonist such as dimetinden (Fenistil) 3 times/day 1-2 mg p.o. with an H ₂ antagonist such as cimetidine (e.g. Tagamet) 400-800 mg/day p.o. are used. S.a.u. Mastocytosis, systemic.
• Mast cell stabilizers (e.g. ketotifen (e.g. zadite cps/syrup): adults: 2 times/day 1-2 mg p.o., children over 3 years: 2 times/day 1 cps, children from 6 months to 3 years: 2 times/day 2.5 ml syrup.
• In individual cases, improvement is achieved under disodium cromoglicic acid (e.g. Colimune) 4 times/day 100-200 mg.
• Glucocorticoids: In severe, including bullous forms, glucocorticoids in medium dosages such as prednisone (e.g. Decortin) 40-60 mg/day may be considered, gradual dose reduction until the maintenance dose is reached according to the clinic.
• Experimental approaches with positive results exist for Omalizumab (Xolair), an IgE antibody.

Cheap. > 95% of patients have a normal life expectancy.

In >50% of juvenile mastocytoses there is spontaneous remission until adolescence. Systemic involvement can be demonstrated in 10% of children. Especially also in children with a later first manifestation (>years). Clinical signs of systemic involvement may include diarrhoea, flush, headache and bone pain.

In adult Urticaria pigmentosa the disease generally progresses chronically, insidiously progressive. Only a small part shows remissions. A systemic involvement is observed in about half of the patients. Systemic involvement (mast cell infiltrations in bone marrow, liver, spleen and/or lymph nodes) are observed and manifest themselves in a variety of organ diseases such as gastritis, ventriculitis or duodenal ulcer, flush, malabsorption syndrome.

Antihistamines for Urticaria pigmentosa

1. Arber DA et al (2016) The 2016 revision to the World Health Organization classification of myeloidneoplasms
   and acute leukemia. Blood 127:2391-405.
2. Czarnetzki BM et al (1985) Phototherapy of urticaria pigmentosa; clinical response and changes of cutaneous reactivity, histamies and chemotactic leukotrienes. Arch Dermatol Res 277: 105-113
3. Comte C et al (2003) Urticaria pigmentosa localized on radiation field. Eur J Dermatol 13: 408-409
4. Gobello T et al (2003) Medium versus high-dose ultraviolet A1 therapy for urticaria pigmentosa: a pilot study. J Am Acad Dermatol 49: 679-684
5. Guler E et al (2001) Urticaria pigmentosa associated with Wilms tumor. Pediatric Dermatol 18: 313-315
6. Ludolph-Hauser D et al (2001) Occult cutaneous mastocytosis. dermatologist 52: 390-393
7. Nettleship E (1869) Rare forms of urticaria. Br Med J 2: 323
8. Nettleship E (1869) Chronic urticaria leaving brown stains: nearly two years' duration. BMJ 2: 435
9. Requena L (1992) Erythrodermic mastocytosis. Cutis 49: 189-192
10. Sangster A (1878) Urticaria Pigmentosa. Lancet I: 683