Rogier Heide

Effect of Starvation and Subsequent Refeeding on Thyroid Function and Release of Hypothalamic Thyrotropin-Releasing Hormone

Effects of starvation on thyroid function were studied in 5- to 6-week-old (R x U) F1 rats. Starvation lowered plasma TSH in female, but not in male rats. Plasma T4 and T3 levels decreased, whereas the dialysable T4 fraction increased during starvation. Free T4 (FT4) levels decreased rapidly in females, but only after prolonged fasting in male rats. Glucose decreased, and free fatty acid levels increased during starvation. Peripheral TRH levels did not change during food deprivation. Since effects of starvation were most apparent in young female rats, such rats were used to study hypothalamic TRH release during starvation and subsequent refeeding. Basal in vitro hypothalamic TRH secretion was less in starved rats than in control or refed animals. In vitro hypothalamic TRH release in medium with 56 mM KCl increased 3-fold compared to basal release, and in these depolarization conditions TRH release was similar between hypothalami from control, starved and refed rats. In rats starved for 2 days, TRH level in hypophysial portal blood was lower than that of controls. Thus, diminished thyroid function during starvation may at least in part be caused by a reduced hypothalamic TRH release.

Mastocytosis in children: a protocol for management.

Abstract:  Mastocytosis is characterized by an increased number of mast cells with an abnormal growth and accumulation in one or more organs. In most children mastocytosis is limited to the skin (cutaneous mastocytosis) and often transient as compared with that in adults in whom mastocytosis is usually progressive and systemic. Generally, we recognize three more common forms of cutaneous mastocytosis: maculopapulous mastocytosis (formerly urticaria pigmentosa), mastocytoma of skin, and diffuse cutaneous mastocytosis. Childhood mastocytosis can further be divided into cutaneous mastocytosis (nonpersisting and persisting) and systemic mastocytosis (extremely rare). An approach to management using a set protocol is described in table form. In most cases of mastocytosis, only yearly checkups are necessary and no treatment is required; preventive recommendations are warranted in those individuals with systemic disease and constitutional symptoms. Symptomatic therapy is advised in only a minority of cases. This article is meant as a guideline for physicians involved in the care of children with mastocytosis and their parents.

Comparison of mastocytosis with onset in children and adults

Objective To compare the incidence, symptomatology and course of mastocytosis with onset in childhood and in adults.

Mast cell distribution in normal adult skin

Aims: To investigate mast cell distribution in normal adult skin to provide a reference range for comparison with mastocytosis. Methods: Mast cells (MCs) were counted in uninvolved skin adjacent to basal cell carcinomas and other dermatological disorders in adults. Results: There was an uneven distribution of MCs in different body sites using the anti-tryptase monoclonal antibody technique. Numbers of MCs on the trunk, upper arm, and upper leg were similar, but were significantly different from those found on the lower leg and forearm. Two distinct groups were formed—proximal and distal. There were 77.0 MCs/mm2 at proximal body sites and 108.2 MCs/mm2 at distal sites. Adjusted for the adjacent diagnosis and age, this difference was consistent. The numbers of MCs in uninvolved skin adjacent to basal cell carcinomas and other dermatological disorders were not different from those in the control group. Differences in the numbers of MCs between the distal and the proximal body sites must be considered when MCs are counted for a reliable diagnosis of mastocytosis. A pilot study in patients with mastocytosis underlined the variation in the numbers of MCs in mastocytosis and normal skin, but showed a considerable overlap. The observed numbers of MCs in adults cannot be extrapolated to children. Conclusions: MC numbers varied significantly between proximal and distal body sites and these differences must be considered when MCs are counted for a reliable diagnosis of mastocytosis. There was a considerable overlap between the numbers of MCs in mastocytosis and normal skin.

Mastocytosis in childhood.

Mastocytosis is a primary, abnormal accumulation of mast cells in the absence of an apparent cause. Mast cell infiltrates may be present anywhere in the body. The skin is the most frequent site of involvement (1,2). Mastocytosis is associated with a broad range of local and systemic symptoms primarily caused by the release of mast cell mediators. Adult-onset mastocytosis and childhood onset mastocytosis vary in both clinical symptoms and course. They also differ in association with genetic mutations of growth factor receptor c-kit. In this review, attention has been focused on pediatric mastocytosis.

Clinical Aspects of Diffuse Cutaneous Mastocytosis in Children: Two Variants

Objective: This paper describes two different clinical presentations of diffuse cutaneous mastocytosis (DCM), based on the largest series published to date. As far as we are aware, these two variants of clinical presentations have not yet been reported. Design: We undertook a case controlled analysis of 8 children with DCM. Results of laboratory testing including mast cell mediator levels, and clinical symptoms on presentation and during follow-up were analyzed. Results: The levels of relevant mast cell mediators were initially high in all cases but declined sharply later on. There was a reduction of 20% in 2 of the 7 cases, whereas there was a reduction of 80% in the remaining 5. No reduction occurred in 1 case. Clinical improvement followed the same pattern. Conclusions: DCM is a rare variant of cutaneous childhood onset mastocytosis. Various forms show the same or overlapping features at various times. It appears to follow a course similar to that in other types of childhood onset mastocytosis, taking into account the decreased symptoms and the levels of mast cell mediators during follow-up. Obtaining a bone marrow biopsy should be considered only in those cases where there is no improvement or even worsening of signs or symptoms and persistent elevated levels of mast cell mediators.

Serum tryptase and SCORMA (SCORing MAstocytosis) Index as disease severity parameters in childhood and adult cutaneous mastocytosis

Background.  Skin lesions are the predominant clinical feature of the commonest form of mastocytosis. Mastocytosis is classified according to World Health Organization criteria. Determination of the levels of mast‐cell mediators or their metabolites reflects the mast‐cell burden. The extent of cutaneous mastocytosis can be assessed clinically using a scoring system (SCORing MAstocytosis; SCORMA Index) that we have developed.

Clinical Scoring of Cutaneous Mastocytosis

There are still many controversies in defining and evaluating mastocytosis. One of the aspects that is missing is a system for clinical evaluation of mastocytosis of the skin. A calculation based on a semi-quantitative analysis of three aspects of mastocytosis was designed. The method is called the scoring index of mastocytosis (SCORMA). The clinical use of SCORMA is advocated.

Efficacy of 25% Diluted Fluticasone Propionate 0.05% Cream as Wet-Wrap Treatment in Cutaneous Mastocytosis

Background: Mastocytosis is a disorder that can be subdivided into two forms: cutaneous and systemic. Patients with cutaneous mastocytosis only may suffer from cosmetic problems. Topical steroid application has been shown to be effective in cases of limited skin lesions. Methods: A case-controlled pilot study was conducted during a 6-weeks treatment using diluted 25% fluticasone propionate 0.05% cream under wet-wrap occlusion in 5 adults and 6 children. Improvement was measured up to the 24th week after treatment using the SCORMA Index. Results: The results of this pilot study showed a partial but clear cosmetic improvement in 9 of the 11 patients. The mean SCORMA Index decreased after treatment from 38 to 26. Conclusion: 25% dilution of fluticasone propionate 0.05% cream under wet-wrap occlusion is an alternative treatment modality for alleviating the symptoms of cutaneous mastocytosis, but the improvement may be moderate and fall short of the patient’s expectations.

Recent advances in mast cell-related skin diseases: particular focus on mastocytosis and urticaria

Mast cells have a prominent, although not completely understood, participation in both immunity and disease. Well-known disorders in which mast cells play a prominent and undisputed role are mastocytosis and urticaria. Mastocytosis has been classified more clearly, based on international consensus meetings and reports of the European Network on Mastocytosis (Consensus Mastocytosis 2007) in the last 5 years. Urticaria is elicited by a great diversity of factors and entities. Treatment points at avoidance, elimination or treatment of the eliciting stimulus or cause, inhibition of mast cell mediator release or therapy of target tissues of mast cell mediators (Consensus Urticaria 2006). Chronic urticaria is believed to have an underlying autoimmune pathogenesis in almost 50% of cases. In a disease such as atopic dermatitis, the role of mast cells is probably underexposed, but is beyond the main scope of this review. In this review; we stress the important differences between children and adults with these dis...