Immunohistochemical demonstration of migration inhibitory factor in different types of urticaria

Because urticarial lesions can persist for extended periods of time, we have investigated the histochemical expression of an antibody against the cytokine macrophage inhibitory factor in 23 patients with different types of urticaria. Positive staining of upper and middermal dendritic cells was noted in sections from all three biopsy specimens of acute urticaria, eight of chronic urticaria, and all six of urticaria pigmentosa lesions. In all but one biopsy specimen, endothelial cells reacted as well. In three sections (two chronic urticaria, one urticaria pigmentosa), luminal lining cells of sweat glands were also noted to stain positively. In contrast, lesional skin from all eight patients with pressure urticaria was negative, as was the clinically normal skin of all patients, with the exception of one patient with urticaria pigmentosa. The data suggest that cytokines may be involved in lesions of acute type immunologic processes and that they need not be expressed in delayed type reactions.     

Familial urticaria pigmentosa associated with thrombocytosis as the initial symptom of systemic mastocytosis and Down''s syndrome

Most cases of urticaria pigmentosa are confined to the skin, but visceral involvement and/or haematological abnormalities have been observed. It is still a matter of debate whether all forms of mastocytosis are true neoplasias or reactive hyperplasias. Familial inheritance of urticaria pigmentosa is rare. We report on a fraternal set with urticaria pigmentosa as part of a systemic mastocytosis. The first patient additionally revealed persistent thrombocytosis and splenomegaly. His brother developed urticaria pigmentosa, intermittent diarrhoea, hepatomegaly and asthma bronchiale associated with trisomy 21 (Down's syndrome). The association of mastocytosis with thrombocytosis has seldom been described. In our patient it preceded the development of systemic mastocytosis. The association with Down's syndrome has not been reported until now.     

Macrophage subsets in different types of urticaria

Summary Biopsy specimens from lesional and uninvolved skin of nine patients with delayed pressure urticaria, three patients with acute urticaria, six patients with chronic recurrent urticaria, and four patients with urticaria pigmentosa were analyzed by routine histology and by immunochemistry for their reactivity with monoclonal antibodies to three different subsets of macrophages. Skin from 12 healthy volunteers served as control. Uninvolved skin of patients did not differ from that of healthy volunteers. An antibody against activated macrophages (27E10) was reactive to a marked extent with macrophages in wheals of pressure urticaria, more variably in acute and chronic urticaria, and practically not at all in urticaria pigmentosa. Antibodies with specificities for macrophages in healing (RM3/1) and normal (25F9) tissue reacted more markedly in all but pressure urticaria lesions, compared with normal skin. These findings indicate an active involvement of inflammatory macrophages in whealing reactions while these cells play apparently no role in cutaneous mast cell proliferation (urticaria pigmentosa).     

Urticaria pigmentosa coexisting with multiple myeloma

We present the case of a 44-year-old white male who developed multiple myeloma complicated by acute renal failure S years after the onset of urticaria pigmentosa. Mast cell disease has been associated with a number of haematological malignancies, particularly those from the myeloid lineage. Lymphoproliferative disorders have also been linked with mast cell disease but an association with multiple myeloma has not previously been described. Patients with urticaria pigmentosa should undergo simple screening blood tests to exclude an underlying haematological malignancy.     

Perivascular mast cells in urticaria pigmentosa

We have quantified perivascular mast cells in cases of urticaria pigmentosa, urticaria, and dermal hypersensitivity reactions. To facilitate reproducibility, the mast cells were counted for a precisely defined vessel unit. These vessel units were divided arbitrarily into those ≤55μm and > 55μm in largest diameters. Urticaria pigmentosa showed an average of 6.4 ± 1.9 and 22.8 ± 13.2 masts cells for vessel unit ≤ 55μm and ≤ 55μm, respectively. Urticaria yielded a lower number of mast cells: 1.5 ± 0.2 and 2.9 ± 0.9 for the same respective vessel units. Dermal hypersensitivity reactions revealed an average of 1.6 ± 0.4 and 2.2 ± 0.7 mast cells, and the normal skin showed 1.5 ± 0.3 and 2.4 ± 0.6 mast cells for each of the vessel units of ≤ 55μm and > 55μm. The perivascular mast cell distributions of urticaria pigmentosa are statistically different from those of urticaria and dermal hypersensitivity reactions with p < 0.0001. No statistical difference was noted between urticaria, dermal hypersensitivity reactions, and normal skin. The percentages of vessel units ≤ 55μm with ≥ 5 mast cells and vessel units < 55μm with ≥ 10 mast cells were determined for each case. The average percentage of vessel units for the former and latter in urticaria pigmentosa was 82.6% and 58.9%, respectively. Urticaria yielded 0% and 0.2%, respectively. None of vessel units in the dermal hypersensitivity reactions or normal skin contained more than 5 mast cells in vessel units ≤ 55μm and more than 10 mast cells in vessel units > 55μm. Cases of urticaria pigmentosa can be distinguished from other cutaneous eruptions containing mast cells using a simple counting technique on Giemsa stained sections.     

Analysis of c-kit exon 11 and exon 17 of urticaria pigmentosa that occurred in monozygotic twin sisters

Genomic DNA extracted from peripheral blood mononuclear cells of monozygotic twin patients with urticaria pigmentosa was investigated for mutations of proto-oncogene c-kit. Neither the patients nor their families had genomic mutations in exon 11 or exon 17 of c-kit. The patients did not have any systemic involvement or bone marrow abnormalities. There are indications that some genetic factors may participate in the pathogenesis of urticaria pigmentosa in monozygotic twins. In the present patients, factors other than genomic faults in exon 11 and exon 17 of c-kit may be responsible for the pathogenesis.     

Increased tryptase levels in suction-blister fluid from patients with urticaria

The levels of tryptase in the suction-blister fluid from patients with chronic urticaria, urticaria pigmentosa, cholinergic urticaria, urticarial dermographism, prurigo of unknown origin, eczema, psoriasis, atopic dermatitis, and from healthy controls were studied. The blister fluid from controls contained up to 15 micrograms/l of tryptase, whereas that from patients with active urticaria contained greater than 50 micrograms/l. This study demonstrates that patients with urticaria have mast cells that readily release tryptase in both the lesional and non-lesional areas of skin.     

Dermatoscopic findings of urticaria pigmentosa

Mastocytosis is a rare disease characterized by proliferation and accumulation of mast cells in various organs. The maculopapular cutaneus mastocytosis is divided into three subtypes: papular/plaque variant, urticaria pigmentosa and eruptive macular telangiectasia perstans. Dermoscopic may help to better characterize the different forms of cutaneus mastocytosis. We report a 55 year-old female with urticaria pigmentosa and its dermoscopy.     

Coexistent urticaria pigmentosa, acromegaly and acanthosis nigricans

We report a case of urticaria pigmentosa, acromegaly and acanthosis nigricans in a 25-year-old male. The patient exhibited multiple pigmented papules on the trunk and the extremities. Histological examinations of the papules revealed infiltrates of mast cells in the upper dermis. Ultrastructurally, the mast cells were fully matured and exhibited no atypical features. A typical appearance of acromegaly, frontal bossing, prominence of the jaw and bony overgrowth and cutaneous changes of acanthosis nigricans on the neck, the axillae and the groins were observed. Growth hormone hypersecretion and insulin resistance were detected in the patient. A pituitary tumor was found and resected surgically. After the operation, endocrinological abnormalities and cutaneous manifestations of acanthosis nigricans improved markedly. As far as we know, this is the first report of the coexistence of urticaria pigmentosa, acromegaly and acanthosis nigricans.     

Photochemotherapy (PUVA) in the treatment of urticaria pigmentosa

Eight patients received PUVA for mastocytosis. Five women had typical adult-onset urticaria pigmentosa, without evidence of systemic disease. Another woman had suspected hepatic involvement while the remaining female had early-onset familial urticaria pigmentosa with morphologically atypical mast cells. The only male patient had cirrhosis with hepatic deposits of mast cells in addition to polycythaemia rubra vera. In all patients, except the man with systemic disease, there was reduced pruritus and wealing and partial to almost complete fading of the macules. The manifestations of urticaria pigmentosa recurred after treatment was discontinued. In both lesional and uninvolved skin there was no significant change in either the mean mast cell counts or mast cell ultrastructure after an average of twenty-seven PUVA exposures. In addition, PUVA did not cause a significant alteration in the histamine content of the skin. The beneficial effect of PUVA in urticaria pigmentosa therefore does not appear to be directly related to a change in mast cell numbers or morphology, or to the histamine concentration in the skin. Urticaria pigmentosa usually presents as a generalized maculo-papular rash which urticates on rubbing (Darier's sign). Many patients are troubled only by the unsightliness of the rash while some complain of pruritus, wealing or flushing. These symptoms are attributed to the release of histamine by mast cells which characteristically occur in increased numbers in the dermis. Symptomatic treatment is often unrewarding, but favourable results have been claimed for cimetidine with or without Hi blockers (Hirschowitz & Groarke, 1979; O'Laughlin & Bredfeldt, 1980) and for oral disodium cromoglycate (Soter, Austen & Wasserman, 1979; Czarnetski & Behrendt, 1981). In 1978, Christophers and colleagues reported that photochemotherapy (PUVA) produced symptomatic relief in all of ten adult patients with typical urticaria pigmentosa. Similarly encouraging results were subsequently reported from other centres (Ortonne et al., 1980; Allevato, Donatti & Cordero, 1980; Granerus, Roupe & Swanbeck, 1981; Väätäinen, Hannuksela & Karvonen, 1981). In this study we examined the effects of PUVA in eight adult patients with urticaria pigmentosa. Although PUVA produced a moderately good clinical response in seven out of these eight patients (reduced pruritus, reduced wealing and faded macules) quantitative studies failed to reveal a consistent effect of PUVA on either the mast cell population density or the histamine concentration in both lesional and clinically uninvolved skin. The findings arc discussed in relation to existing information concerning the effect of ultraviolet radiation (U VR) on mast cells and other constituents of the skin.     

183例儿童皮肤型肥大细胞增生症临床及预后分析

目的 探讨儿童皮肤型肥大细胞增生症的临床特征及预后。 方法 回顾分析183例儿童皮肤型肥大细胞增生症患者的临床资料,并随访部分患者。 结果 183例患者中,色素性荨麻疹136例（74.3%）,肥大细胞瘤43例（23.5%）,弥漫性肥大细胞增生症4例（2.2%）;生后2岁内发病者179例（97.8%）。43例肥大细胞瘤患者中出生即发病者21例（48.8%）,出生后至6个月发病者17例（39.5%）,136例色素性荨麻疹患者中出生即发病者35例（25.7%）,出生至6个月发病者78例（57.3%）。伴随症状记录详细的33例患者中,10例出现伴随症状,其中9例为潮红发作。对45例患者随访3 ~ 6年（平均4年）,色素性荨麻疹患者1例于11岁时皮损完全消退,18例皮损部分消退;肥大细胞瘤患者1例皮损于8岁时完全消退,7例行皮肤活检后1年内皮损消退。口服抗组胺药可控制患者潮红、风团及水疱等症状;口服糖皮质激素可有效控制弥漫性肥大细胞增生症患儿反复发生的泛发水疱、大疱。 结论 儿童皮肤型肥大细胞增生症以色素性荨麻疹最常见,其次为肥大细胞瘤。肥大细胞瘤多于出生即发病,而色素性荨麻疹以出生后至6个月发病多见。口服抗组胺药可控制介质释放相关症状。严重的弥漫性肥大细胞增生症患者可口服糖皮质激素控制症状。     

Okkulte kutane Mastozytose

Mastocytosis is diagnosed without difficulty if it presents with easily recognizable lesions of urticaria pigmentosa. Recently, we have identified hardly visible skin lesions of mastocytosis in Hymenoptera venom allergic patients ("occult mastocytosis"). In addition, in approximately 15% of the patients with typical cutaneous lesions, urticaria pigmentosa was at first mistaken for other conditions and thus not linked to simultaneous symptoms of systemic mastocytosis. In most patients with unrecognized mastocytosis, the diagnosis was supported by raised basal serum tryptase levels. Cutaneous mastocytosis is often overlooked and more frequent than assumed. Measurement of basal serum tryptase concentrations can make an important contribution to the diagnosis of mastocytosis, but it does not replace a meticulous skin examination.     

Malignant melanoma and systemic mastocytosis—a possible association?

Lymphoproliferative and myeloproliferative malignancies have been noted in patients with systemic mastocytosis and urticaria pigmentosa. However, to our knowledge an association between mastocytosis and malignant melanoma has not been reported previously.     

Urticaria pigmentosa localized on radiation field

A woman previously treated by radiotherapy for a breast cancer developed urticaria pigmentosa mainly restricted to the irradiation field, without any systemic symptoms. Localized forms of urticaria pigmentosa are exceptional, and their triggering factors are poorly understood. Several hypotheses can be discussed in this peculiar observation, among which a direct role of radiotherapy in the occurrence of cutaneous lesions cannot be ruled out.     

Intestinal mucosal mast cells: enumeration in urticaria pigmentosa and systemic mastocytosis

Endoscopic gastrointestinal mucosal biopsy specimens from one patient with systemic mastocytosis and five with urticaria pigmentosa (UP) were fixed with Carnoy's reagent and then stained for chloracetate esterase. The mast cell population densities were enumerated in the mucosa using cursor planimetry. Compared with controls, mast cell counts were increased in gastric and duodenal but not sigmoid mucosae. On a histological basis, systemic involvement would appear commoner in urticaria pigmentosa than is generally expected. Gastrointestinal symptoms did not relate to elevated mucosal mast cell counts.     

Serum tryptase measured with B12 and G5 antibody-based immunoassays in mastocytosis patients and its relation to histamine turnover

Serum tryptase was measured with the B12 and G5 antibody-based immunoassays in 25 adult patients with mastocytosis and in 18 controls. Twelve patients had uncomplicated cutaneous mastocytosis (urticaria pigmentosa) and 13 had urticaria pigmentosa with systemic symptoms. Tryptase levels were compared with histamine turnover estimated as urinary excretion of the main histamine metabolite tele-methylimidazoleacetic acid. Elevated B12 tryptase levels (> 20 μg/L) were found in most mastocytosis patients, including five of eight patients with only cutaneous manifestations who had a low urinary histamine metabolite excretion. This indicated a higher sensitivity for diagnosing mild mastocytosis on the basis of levels of serum tryptase as opposed to urinary methylimidazoleacetic acid. However, the serum B12 tryptase assay could not differentiate between urticaria pigmentosa patients with and without systemic disease: the measurement of histamine metabolite excretion probably reflects the mast cell burden more accurately. Serum G5 tryptase levels were generally low in both controls and mastocytosis patients.     

URTICARIA PIGMENTOSA IN PATIENTS CLOSELY RELATED BY BIRTH

An occurrence of urticaria pigmentosa in two sisters was studied. The clinical characteristics included the rare location of the lesions in both sisters and an onset after rubeola in the elder sister. Serum histamine levels throughout the family were markedly higher than normal. Investigations into the family medical history failed to disclose clear evidence of any hereditary factor. Perhaps many triggers in addition to hereditary factors are needed to initiate urticaria pigmentosa.     

Ultraviolet phototherapy for pruritus

Ultraviolet-based therapy has been used to treat various pruritic conditions including pruritus in chronic renal failure, atopic dermatitis, HIV, aquagenic pruritus and urticaria, solar, chronic, and idiopathic urticaria, urticaria pigmentosa, polycythemia vera, pruritic folliculitis of pregnancy, breast carcinoma skin infiltration, Hodgkin's lymphoma, chronic liver disease, and acquired perforating dermatosis, among others. Various mechanisms of action for phototherapy have been posited. Treatment limitations, side effects, and common dosing protocols are reviewed.     

Cutaneous mastocytosis: demographic aspects and clinical features of 55 patients

BACKGROUND: Mastocytosis is a rare, heterogeneous group of disorder with abnormal increase of mast cells in one or more organ systems. OBJECTIVE: To evaluate the demographic and clinical features of cutaneous mastocytosis (CM). METHODS: Records of 55 patients with cutaneous mastocytosis were retrospectively analysed. RESULTS: Of the 22 females and 33 males, 80% had urticaria pigmentosa/maculopapular CM and 20% had mastocytoma. Of all cases, 81.8% had first lesions in childhood. The most common presentation was involvement of trunk together with extremities. Thirteen (23.6%) patients had history of bulla; Darier's sign was positive in 34 of 38 patients. Itching was the most common complaint, provocated by hot weather/bath. CONCLUSION: Clinical presentations of urticaria pigmentosa/maculopapular CM and mastocytoma are similar regarding gender, age of onset, age of diagnosis, and presence of Darier's sign and history of bulla. In contrast to mastocytoma, urticaria pigmentosa/maculopapular CM lesions were frequently located on trunk together with extremities.