Urticaria pigmentosa. A case report
M. Slavkovic-Jovanovic, D. Jovanovic, A. Petrovic, D. Mihailovic
S U M M A R Y
We present the case of 22-month-old boy with Urticaria pigmentosa. Clinical feature was presented as disseminated yellow-brownish patches, on the skin of entire body, including skin of the scalp, 1x2 cm in diameter. No subjective symptoms were present. First skin lesion occurred in the second month of life. Darier's sign was positive. Serum triptase levels were elevated. Diagnosis of mastocytosis was confirmed by pathohistology.
Introduction
KEY WORDS
mastocytosis, urticaria pigmentosa, mastocytes
Urticaria pigmentosa is the prototype of mast cell disease. This name is given to a type of cutaneous mas-tocytosis, in which there are yellow-tan to reddish-brown patches on the skin due to abnormal collections of mast cells. (1, 2). It is the most common skin manifestation of mastocytosis in both children and adults (3).
Urticaria pigmentosa was first described by Nettleship and Tay in 1869 (4) as a rare form of urticaria. Unna in 1887 (5) demonstrated the relationship between urticaria pigmentosa and the mast cells. Mastocytosis is defined as an overproliferation and accumulation of tissue mast cells (6, 7, 8, 9, 10). In cutaneous mastocytosis, release of histamine from their granules, leads to urti-carial edema of the lesions, which results in secondary hiperpigmentation due to melanocytic activity at the dermoepidermal junction (11).
Mast cells were first described by Erhlich (12, 13). Mast cells are normally widely distributed in the skin. They contain granules that contain histamine and other mediators of inflamation. When the mast cell is irritated, these chemicals are released into the surrounding skin, causing leaking of the blood vessels, resulting in localized itching, swelling and redness (2).
Urticaria pigmentosa most often affects infants. In more than 50%, the onset is before 2 years of age (14). Usually the first skin lesions appear at a few months of age. They persist and gradually increase in number for several months or years. They can appear on any part of the body including the scalp, face, trunk and limbs. There is no sex preference (2, 3, 11, 14).
Clinical feature consist of reddish or brownish patches on the skin, with dissemination of variable density. Trunk
Figure 1. Disseminated reddish-brown patches
on the skin of the back side of the body (with
the site of the biopsy on the left)	Case report
is the most common site of the lesions but they can also present on the other parts of the body. Lesions are variable in size, round or oval, while nodular or tumor-like elevations are uncommon. Usually variable amount of pruritus may be present 2, 3, 11, 14).
Over the next few years the urticaria pigmentosa becomes less irritable and eventually the patches fade away. By the teenage years, most patches will resolve spontaneously (2, 3, 14).
Rubbing of a cutaneous mastocytosis lesion within a few minutes results in the formation of a wheal or even a vesicle. This characteristic response is known as Darier's sign and is considered clinically diagnostic (15). The diagnosis of urticaria pigmentosa made clinically, it should be confirmed by histopathology (3, 16).
Although in 90% of patients there are no evidence of systemic involvement (14), sometimes urticaria pigmentosa may be associated by ulcers, malabsorption, bone abnormalities, hepatomegaly, splenomegaly, lymphadeno-pathy, peripheral blood abnormalities, elevated levels of plasma or urinary histamine or histamine metabolites, prostaglandin D2 and other metabolites in urine or plasma (3).
22-month-old boy was admitted to the Clinic of pediatry. On the skin of the entire body, including skin of the scalp disseminated yellow-brownish patches were present, 1x2 cm in diameter. No subjective symptoms were present.
First skin lesion occurred in the second month of life on the skin of the neck and upper extremities, as reddish infiltrates. Therapy with topical corticosteroids prescribed by the general practitioner showed no effect. Lesions have spread to the skin of the entire body including the scalp (Fig. 1). In consultation with dermatologist diagnosis of urticaria pigmentosa was made. Darier's sign was positive.
Skin biopsy of a lesion from the trunk was taken. Specimens were stained by haematoxylin-eosin (HE), and Unna's method for mast cells (17). Pathohistological examination confirmed diagnosis of mastocytosis. HE staining showed massive lymphocytic infiltrate in dermis (Fig. 2), while Unna's staining confirmed that great majority of cells in infiltrate were mastocytes.
Personal history: Second child from second pregnancy. Delivery was on term. Breast feeded 14 months. No other health problems reported by parents.
The family history relevated that the grandfather (fathers' side) allegedly had some similar skin disease in childhood.
Physical examinations including cardiology, pulmo-nology, neurology, ophthalmology, ECG examinations and echosonography of abdomen were without disturbances.
Laboratory analyses: Serum tryptase levels were elevated, 21 ng/mL. Normal values are up to 11.5 ng/mL (18). Other laboratory analyses (blood cell counts and biochemistry parameters) of blood and urine were within normal limits.
Patient was followed during one year. There were no clinical changes and no new lesions appeared. Since there is not involvement of other systems, except skin, it can be expected that lesions may regresse during next years.
Discussion
Cutaneous mastocytosis is a condition characterized by mast cell hyperplasia in the skin. Urticaria pigmentosa is the most frrequent manifestation of cutaneous masto-cytosis. The lesions of urticaria pigmentosa appear as small yellow-tan to reddish-brown macules or slightly raised papules disseminated on the skin of the body. The palms, soles, face and scalp may be free of lesions (3). Usually the first skin lesions appear at a few months age. Mild trauma, scratching or rubbing of the lesion may led to urtication and erythema around the lesion which is known a Darier's sign. The condition is accompanied by variable degree of pruritus (3). Sytemic involvement
R EFER ENCES -
is rare in urticaria pigmentosa (14).
In our patient, disease occured in the second month of life. Clinical feature is typical for urticaria pigmentosa, including reddish-brown macules and slightly raised plaques on the skin of the entire body. Lesions were present also on the skin of the neck and scalp which is not so usual. Darier's sign was positive.
Blood cell count was within normal values, wich is in accordance with cutaneos mastocytosis, while in systemic mastocytosis, it may reveal anemia, thrombocy-topenia, thrombocytosis, leukocytosis, and eosinophilia (3, 14 19).
If a diagnosis of mastocytosis is uncertain, tests for elevated mast cell mediators and degradation products may help establish the diagnosis. Serum tryptase levels are elevated in patients with mastocytosis. Our patient also had elevated serum triptase levels. Tryptase levels may be more useful than histamine levels, because his-tamine can be elevated in hypereosinophilic states (19). Urinary A-methylhistamine (NMH) and A-methylimi-dazoleacetic acid levels may be more specific and sensitive than urinary histamine levels. NMH levels correlate directly with the extent of skin lesions. Urinary pros-taglandin D2 metabolite levels, even during asymptomatic periods, may exceed the normal level 1.5-150 times (19).
In conclusion, according to the clinical feature, positive Darier's sign, elevated serum triptase level and pathohistological examination, diagnosis of Urticaria pigmentosa was confirmed. Since this is a form of cutaneous mastocytosis, without systemical involvement, prognosis is good and it can be expected that lesion will resolve during next few years.
1.	AE Kiszewski, C Duran-Mckinster, L Orozco-Covarrubias, P Gutierrez-Castrellon, R Ruiz-Maldonado. Cutaneous mastocytosis in children: a clinical analysis of 71 cases. JEADV 2004; 18: 285-290.
2.	Urticaria pigmentosa. At: http://dermnetnz.org.
3.	Metcalfe DD. The Mastocytosis syndrome. In: Dermatology in general medicine. Eds: Fitzpatrick TB, Eisen AZ, Wolff K, Freedberg IM, Austen K. McGraw-Hill Inc, New York, 1993: 2017-23.
4.	Nettleship E, Tay W. Rare form of urticaria. Br Med J 1869; 2:323-30.
5.	Unna PG. Anatomie und pathogenese der urticaria simplex und pigmentosa. Monatschr Prakt Dermatol 1887; 6: EH1.
6.	Longley J, Duffy TP, Kohn S. The mast cell and mast cell disease. J Am Acad Dermatol 1995; 32: 54561.
7.	Galli SJ. New concepts about the mast cell. N Engl J Med 1993; 328: 257-65.
8.	Lazarus GS. Mastocytosis: new understandings in cutaneous pathophysiology. J Dermatol 1996; 23: 769-72.
9.	Longley J. Is mastocytosis a mast cell neoplasia or a reactive hyperplasia? Clues from study of mast cell growth factor. Ann Med 1994; 26: 115-16.
10.	Golkar L, Bernhard DJ. Mastocytosis. Lancet 1997; 349: 1379-85.
11.	Braun-Falco O, Plewig G, Wolff HH, Winkelmann RK. Mastocytosis. In. Dermatology. Eds: Braun-Falco O, Plewig G, Wolff HH, Winkelmann RK. Springer-Verlag, Berlin, 1991: 1107-12.
12.	Ehrlich P. Beiträege zur Kenntnis der Anilinfaerbungen und ihrer Verwendung in der mikroskopischen Technik. Arch Mikr Anat 1877; 13 : 263-77.
13.	Erlich P. Uber die specifichen granulationen das blutes. Archiv Physiologie, 1879, 571-9.;
14.	Greaves MW. Mastocytoses. In: Rook/Wilkinson/Ebling Textbook of dermatology, Eds: Champion RH, Burton JL, Ebling FJG. Blackwell Scientific publicatons, Oxford, 1992: 2065-72.
15.	Tharp MD. Southwestern Internal Medicine Conference: the spectrum of mastocytosis. Am J Med Sci 1985; 289: 117-132.
16.	Garriga MM, Friedman MM, Metcalfe DD. A survey of the number and distribution of mast cells in the skin of patients with mast cell disorders. J Allergy Clin mmunol 1988, 82: 425.
17.	Luna, LG. Manual of Histologic Staining Methods of the Armed Forces Institute of Pathology. McGraw-Hill Book Co., New York, 1968: 115.
18.	Klion AD, Noel P, Akin C, Law MA, Gilliland DG, Cools J, Metcalfe DD, Nutman TB. Elevated serum tryptase levels identify a subset of patients with a myeloproliferative variant of idiopathic hypereosinophilic syndrome associated with tissue fibrosis, poor prognosis, and imatinib responsiveness. Blood, 2003, 101 (12): 4660-6.
19.	Hogan D. Mastocytosis. www.emedicine.com/derm/topic258.htm
AUTHORS' Maja Slavkovič-Jovanovič, MD, MSc, Clinic of pediatry, Clinical centre ADDRESSES Niš, Igmanska 38, 18000 Niš, Serbia, e-mail: bukid@eunet.yu
Dragan Jovanovič, MD, PhD, Clinic of dermatology, Clinical centre Niš, Department of dermatovenereology, Medical faculty, University of Niš, Igmanska 38, 18000 Niš, Serbia, e-mail: bukid@eunet.yu Alesandar Petrovič, MD, MSc, Department of histology and embriology, Medical faculty, University of Niš, Bul. Dr Zorana Dindiča 81, 18000 Niš, Serbia, e-mail: aca@medfak.ni.ac.yu
Dragan Mihailovič, MD, PhD, Institute of pathology, Clinical centre Niš, Department of pathology, Medical faculty, University of Niš, Bul. Dr Zorana Dindiča 48, 18000 Niš, Serbia, e-mail: mihapat@ni.ac.yu