Diffuse Cutaneous Mastocytosis: A Current Understanding of a Rare Disease.

Mastocytosis is a heterogeneous disease characterized by the expansion and accumulation of neoplastic mast cells in various tissues. Diffuse cutaneous mastocytosis (DCM) is a rare and most severe form of cutaneous mastocytosis, which typically occurs in childhood. There have been reports of a familial DCM with specific gene mutations, indicating both sporadic and hereditary factors involved in its pathogenesis. DCM is associated with severe MC mediator-related symptoms and an increased risk of anaphylaxis. The diagnosis is based on the appearance of skin lesions, which typically show generalized thickening, erythroderma, blistering dermographism, and a positive Darier's sign. Recognition, particularly in infants, is challenging due to DCMs resemblance to other bullous skin disorders. Therefore, in unclear cases, a skin biopsy is crucial. Treatment focuses on symptom management, mainly including antihistamines and mast cell stabilizers. In extremely severe cases, systemic steroids, tyrosine kinase inhibitors, phototherapy, or omalizumab may be considered. Patients should be equipped with an adrenaline autoinjector. Herein, we conducted a comprehensive review of literature data on DCM since 1962, which could help to better understand both the management and prognosis of DCM, which depends on the severity of skin lesions, intensity of mediator-related symptoms, presence of anaphylaxis, and treatment response.

Current Challenges in the Diagnosis of Pediatric Cutaneous Mastocytosis.

Pediatric mastocytosis is mostly a cutaneous disease classified as cutaneous mastocytosis (CM), which is characterized by mast cell (MCs) accumulation in the skin and the absence of extracutaneous involvement. Based on the morphology of skin lesions, CM can be divided into three major forms: maculopapular CM (MPCM), diffuse CM (DCM) and mastocytoma of the skin. A positive Darier's sign is pathognomonic for all forms of CM. MPCM is the most common form, presenting with red-brown macules or slightly raised papules. Mastocytoma is characterized by solitary or a maximum of three nodular or plaque lesions. DCM is a rare, severe form which presents as erythroderma, pachydermia and blistering in the infantile period of the disease. CM is associated with MC mediator-related symptoms, most commonly including pruritus, flushing, blistering, diarrhea and cramping. Anaphylactic shock occurs rarely, mainly in patients with extensive skin lesions and a significantly elevated serum tryptase level. Childhood-onset MPCM and mastocytoma are usually benign diseases, associated with a tendency for spontaneous regression, while DCM is associated with severe mediator-related symptoms, an increased risk of anaphylaxis and, in some cases, underlying systemic mastocytosis (SM). In contrast to adults, SM is a rare finding in children, most commonly presenting as indolent SM. However, advanced SM sporadically occurs.

Origin of chromic effects and crystal-to-crystal phase transition in the polymorphs of tyraminium violurate.

Chromic materials are nowadays widely used in various technological applications, however understanding the effect and the possibility of tuning the obtained colour of a material are still challenging. Here a combined experimental and theoretical study is presented on the solvatochromic and crystallochromic effects in the (pseudo)polymorphs of tyraminium violurate. This organic material exhibits a large solvatochromic shift (ca 192 nm) associated with broad colour change (from yellow to dark violet). Tyraminum violurate crystallizes as red crystals of form (I) from water as a solvate, and as an unsolvated form [violet crystals of (II)] from methanol solution. Form (I), when heated, undergoes two crystal-to-crystal phase transformations associated with colour change of the crystals. Crystals of (II) show extreme birefringence (ca 0.46) and high refractive index (n γ above 1.90), which can be correlated with preferential orientation of the resultant dipole moments of the ions. Examination of optical effects (UV-Vis spectra) along with theoretical calculations (QTAIM, atomic and bond polarizabilities) enabled the description of the origin of colour in the studied materials.

Solvomorphs of tyraminium 5,5-diethylbarbiturate: a rare example of the barbiturate R33(12) hydrogen-bond motif and a crystal structure with Z' = 4.

In the past two decades, the solvomorphism phenomenon in organic materials has attracted much attention, especially in the pharmaceutical and materials industries. Cocrystallization with solvent molecules can lead to modified physical and chemical properties of materials. We present here two new solvomorphs (pseudopolymorphs) of tyraminium 5,5-diethylbarbiturate [2-(4-hydroxyphenyl)ethanaminium 5,5-diethyl-2,4,6-trioxotetrahydro-2H-pyrimidin-1-ide, C8H12NO+·C8H11N2O3-] with unusual structural features. Pseudopolymorph (I) follows the symmetry of the P21/n space group and has four tyraminium cations, four barbitalate anions and four molecules of chloroform in the asymmetric unit. Pseudopolymorph (II) crystallizes in the space group R-3c with one tyraminium cation, one barbitalate anion and a small amount of disordered solvent (ethanol and water) located in the cavities. Hirshfeld surface analysis and the Non-Covalent Interaction (NCI) index were used to examine and compare the crystal packing features and intermolecular interactions in (I) and (II). Both materials crystallize with large unit cells and contain nontypical barbitalate ions formed through deprotonation of the barbital N3 position. Pseudopolymorph (I) is an example of a crystal structure with a rarely observed value of Z' = 4. Analysis of the hydrogen-bond patterns in (II) showed an unusual arrangement of three barbitalate anions in R33(12) rings, which is the first example of such a hydrogen-bond motif in barbital structures. The mutual arrangement of the ions in the crystal structure of (II) leads to the formation of specific cavities along the c direction.