R.A.J. Eady

Vascular responses of human skin to injection of substance P and mechanism of action

The mechanism of cutaneous inflammation caused by substance P in human skin was assessed in five subjects receiving i.d. injections (5-405 pmol) at pH 7.2 as compared to histamine (0.08-1.6 nmol), compound 48/80 (100 ng) and solvent control. Both substance P and histamine produced sigmoid dose-response curves for the following parameters: 1 min and 5 min planimetrically measured areas of erythema, and mean diameter of weal. Substance P pretreatment induced tachyphylaxis, as assessed by standard methods with adequate controls, to both histamine and to substance P and vice versa. Erythema following substance P i.d. was not blocked by a constricting band. Diphenhydramine, and to a lesser extent doxantrazole, (but not cimetidine or indomethacin) when assessed as inhibitors after oral pretreatment, did shift dose response curves for histamine and substance P to the right. Light and electron microscopic assessment of mast cells was compared in substance P and solvent control injected human skin. These results support a possible role for substance P in cutaneous inflammation acting either directly or via histamine release from mast cells.

Adenosine triphosphate-evoked vascular changes in human skin: Mechanism of action

Adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), adenosine, adenine and inosine were injected intradermally into the backs of human volunteers. ATP, ADP and AMP evoked weal and flare responses in the skin in a dose dependent manner. The rank order of potency was ATP greater than ADP greater than AMP; other metabolites were apparently inactive. The potency of ATP was approximately 0.002 times that of histamine. In the forearm, cross tachyphylaxis was demonstrated between ATP and histamine weals; also the flare due to injected ATP spread beyond a band which was applied to prevent diffusion, indicating that the flare is neurogenic. Injections of ATP and high doses of ADP produced a sensation of persistent pain, unlike histamine which produced transient pain or itch on some occasions, and saline which was without effect. The possible involvement of histamine, mast cells and prostaglandins in the response was examined. The inhibitory actions of systemic pretreatment with diphenhydramine suggests that the erythema and wealing responses to ATP are at least partly due to ATP-evoked histamine release. Indomethacin, doxantrazole and cimetidine did not alter the ATP reaction.

A new method for recovery of exudates from normal and inflamed human skin

A new method for recovery of exudate from human skin using a suction bulla technique is described. Undiluted exudate was obtained with minimal trauma and analysed for histamine, kinin and prostaglandin (PG)‐like activity, by superfusion cascade bioassay. The PG‐like activity was further characterized by gel partition, gas–liquid and thin‐layer chromatography. PGE2 and PGF2α were further characterized by gas chromatography–mass spectrometry (GC–MS) and PGF2α by radioimmunoassay. Histamine was detected as was kinin‐like activity. Prostaglandins E2 and F2α with their metabolites, were also detected.

Aquagenic urticaria: evidence of cholinergic and histaminergic basis

Two patients with urticaria evoked at the site of contact of skin with water have been studied. Protection of the skin from contact with water by prior application of petrolatum ointment prevented wealing, but removal of the stratum corneum enhanced wealing.

Cold urticaria with vasculitis: report of a case with light and electron microscopic, immunofluorescence and pharmacological studies

An unusual form of essential acquired cold urticaria occurring in a 30‐year‐old woman is reported. Exposure of the skin to cold produced immediate wealing and angio‐oedema with subsequent deep bruising, and severe systemic symptoms.

Actinic reticuloid with Sézary cells

A 65‐year‐old man presented with erythroderma, Sezary cells were present in the peripheral blood on electron microscopy and a skin biopsy revealed mycosis fungoides‐like histology. A provisional diagnosis of Sézary syndrome was made. He proved to be exquisitely sensitive to light with markedly abnormal reactions to UV‐B, UV‐A and visible radiation. By carefully avoiding exposure to light, he has remained well for 2 years and the Sézary cells have not been subsequently detected. The clinical features, histology, photo‐test results and course were all in keeping with a diagnosis of actinic reticuloid and this would appear to be a further benign disorder in which Sézary cells may be found.

Ulcerative sarcoidosis: a rare manifestation of a common disease

Scarcoidosis is a systemic disease with cutaneous involvement occurring in 25% of cases. Ulcerative lesions are extremely rare. In recent reviews of the literature only twenty‐seven possible cases have been recorded (Schwartz, 1982). We describe a further case with unusual features.

Half-and-half cells in lichen planus. A possible clue to the origin and early formation of colloid bodies.

In the course of a study of wound healing in four patients with lichen planus, we found transformed keratinocytes with a hitherto undescribed ultrastructure in both wounded and undisturbed papules. We have called these epidermal cells half‐and‐half cells because they showed changes on the one hand of increased synthetic activity and, on the other hand, of fibrillar transformation closely resembling that seen in fully developed colloid bodies.

Endothelial cell pathology as a marker for urticarial vasculitis: a light microscopic study

Various criteria have been used for the diagnosis of urticarial vasculitis, and for the classification of patients with chronic urticaria. In the present study, semithin Epon‐embedded sections were obtained from fifteen patients using a method of fixation optimal for the preservation and examination of the dermal microvasculature. This allowed patients to be classified according to the presence or absence of significant endothelial cell pathology. This feature proved a more reliable indicator of associated humoral abnormalities than the nature of the perivascular infiltrate as seen on paraffin‐embedded sections. Endothelial cell necrosis per se was a rare event and could not be used as a reliable criterion for the diagnosis of urticarial vasculitis. Most cases showed either endothelial hypertrophy or shrinkage.

The mast cells distribution and morphology

Although it has been reported (Seyle, 1965) that the mast cell* was recognized by von Recklinghausen and other notable figures of his time, the credit for first characterizing the mast cell is due to the discovery by Ehrlich (1877) of the cells ability to stain metachromatically with basic aniline dyes. Indeed, much of our present knowledge of the histology of the mast cell has been derived from numerous studies done by the end of the first quarter of this century. More recent work has taught us about the biochemical nature of the specific granules of mast cells including their ability to store and possibly synthesize heparin, histamine, and in some species, (but excluding man), 5-hydroxytryptamine (for review of chemistry, see Smith, 1963b). Electron microscopy has provided important information about the fine structure of mast cells in health and disease and has helped to clarify species differences in mast cell morphology. Furthermore, it has given insight into sequential cytological changes occurring during the process of histamine release.