Toshiaki Doi

High histamine level in the blister fluid of bullous pemphigoid.

Local activation of mast cells and the subsequent infiltration of eosinophils have been suggested as playing some pathogenetic role in the formation of blistering lesions in bullous pemphigoid (BP). A series of complement activation followed by antigen-antibody reaction at the basement membrane zone (BMZ) has been thought to be responsible for mast cell degranulation. In support of these ideas, a lowmolecular-weight eosinophil chemotactic factor (ECFA), derived from mast cells, has been demonstrated in the blister fluid (BF) [3, 9]. In recent literature, frequent observations of degranulated mast cells or basophils in the papillary and reticular dermis in BP have been reported [4]. In addition, clinically observed urticarial lesions appeared before the development of blistering lesions with eosinophilic spongiosis [7]. But direct evidence of mediator release from mast cells has not been obtained excep~ for ECF-A-like molecules in the BP-BF. In this study, we examined the histamine content of BP-BF as a possible indicator of mast cells activation. BF was collected within a few hours after blister formation had first been noticed from tmtreated patients with BP diagnosed on the basis of clinical and immunohistochemical findings. The data of direct and indirect immunofluorescent studies have been summarized in Table 1. The BF of other blistering diseases, such as epidermolysis bullosa dystrophica, and burn or suction blisters was also subjected to the study described above. The BF was precipitated with 6% perchloric acid and the resultant histamine content of the supernatant was measured. The histamine content of BF was determined by an automated fluorescent

Histamine release in contact urticaria

Cardura ElO is an epoxy reactive diluent which possesses an epoxide group and plays a part in the hardening process. Several epoxy reactive diluents, including Cardura ElO, have proved to be sensitizers in guinea pig testing (I). Sensitivity to this substance has been described previously (2). However, the patient tested was also allergic to epoxy resin, suggesting that the epoxide group was the common sensitizer in both substances. It is probable that sensitization to these diluents may be masked by associated epoxy resin sensitivity (2). Our patient demonstrates an isolated Cardura ElO sensitivity, suggesting that the allergen is other than the epoxide group.

Sebaceous Carcinoma Arising in Nevus Sebaceus

A 53‐year‐old woman had had a pale‐brown lesion on her right cheek and neck from birth. Since she was about 40 years old, part of the lesion had gradually elevated and increased in size. At the first examination, there was a huge mass measuring 110 × 70 × 35 mm on the right cheek. A wide local excision of the area including a superficial parotidectomy and submandibular lymph node dissection was performed, followed by full thickness skin grafting. Histological examination of the tumor revealed an invasive dermal neoplasm characterized by lobes that were composed of foamy cells stained with Sudan‐IV mixed with many atypical cells showing remarkable variation in the shapes and sizes of their nuclei. The surrounding epithelial changes were consistent with nevus sebaceus. From these findings, the gigantic tumor was diagnosed as a sebaceous carcinoma arising in nevus sebaceus.

ACQUIRED COLD URTICARIA

Three patients with idiopathic cold urticaria were treated with either or both cyproheptadine (Histamine H1 receptor antagonist) and cimetidine (Histamine H2 receptor antagonist).

Case of premenstrual syndrome inducing monthly episodes of vesiculobullous eruptions on the face.

Dear Editor, Among manifestations of premenstrual syndrome, anti-progesterone dermatitis (APD) is characterized by: (i) episodic skin disturbance including vesiculobullous eruptions during the ovulatory phase; (ii) positive induction test by administration of progesterone; (iii) positive skin test for progesterone; and (iv) presence of anti-rat ovary antibody in the serum. However, the details of the pathomechanism by which progesterone induces vesiculobullous inflammation on the skin have not yet been elucidated, and there are rather few cases that satisfy those criteria. Herein, we report a case that clinically resembled APD, but immunological and challenge tests did not provide any evidence that progesterone participated in this case. A 49-year-old Japanese female presented episodic vesiculobullous eruptions on the face for several months. The skin disturbance started as an itching sensation on the face several days prior to the next menstruation, then worsened to show vesiculobullous eruptions (Fig. 1), and gradually diminished with the coming of menstruation. Skin biopsy of the eruption demonstrated subepidermal blister formation with a dense infiltration of neutrophils and eosinophils (Fig. 2A,B). Immunohistochemistry did not demonstrate either immune deposition along the basement membrane zone of the perilesional epidermis, nor circulating autoantibodies against any skin components. Examinations for autoantibodies against desmoglein (Dsg)-1, Dsg-3 and BP180 using the enzyme-linked immunosorbent assay method were not performed. Electron microscopy using the reembedding method demonstrated that the blister was formed beneath the lamina densa with dermal remnant under the blister roof (Fig. 2C,D). The eruptions reacted to short-term administration of corticosteroid hormone. Suppression of menstruation with estrogen resulted in prevention of the episode, and administration of clomiphene resulted in induction of vesicles (Fig. 3). However, administration of progesterone did not accelerate the episode, intradermal testing of progesterone was negative, and immunofluorescence testing using rat ovary as a substrate did not demonstrate anti-ovarian antibody in the patient’s serum. In this case, acceleration test of ovulation using clomiphene induced the eruptions, and administration of estrogen, which suppressed ovulation, prevented the skin episode. Therefore, some relations should be supposed between ovulation and skin inflammation. The clinical appearance of blisters was similar to that in autoimmune bullous diseases, but neither immune deposition in the skin nor circulating

Histamine Release by Scraching Inflamed Skin

Scratching is an exacerbating factor of skin diseases. Plasma histamine level was assessed before and after scratching with a scratch device. Inflamed skin of patients with atopic dermatitis released slight but significant amounts of histamine by scratching, but healthy skin was not affected by scratching.

Non-IgG1 nature of cutaneous basophil hypersensitivity factor in contact sensitivity.

Cutaneous basophil hypersensitivity (CBH)-inducing factor was demonstrated in immune sera obtained from dinitrofluorobenzene (DNFB)-sensitized animals 2 weeks after sensitization (DNP-GPS-2W). It showed hapten specificity and worked dose dependently. It was fractionated into a non-gamma-globulin fraction by Sephadex G-150 gel filtration following ammonium sulfate desalting and CM-cellulose chromatography. The factor was eluted into a fraction of a little smaller molecular weight than bovine serum albumin on Sephadex G-150 gel filtration. It passed through an antiguinea pig IgG1 column and was absorbed to a DNP-BGG column. On SDS-PAGE it failed to show any staining band because of low protein concentration. From these results CBH factor appearing in circulation in contact-sensitized animals was thought to be a somewhat different molecule from that of Askenases factor, i.e. IgG1 antibody.

POSSIBILITY OF PASSIVE TRANSFER OF COLD URTICARIA TO GUINEA PIGS

Serum from one out of six patients with idiopathic acquired cold urticaria produced a short lived edematous reaction in the pinna of guinea pigs 24 hours after intradermal injection of the patients serum and subsequent cold challenge. No relationship was observed between the transfer activity and IgE titer or atopic status.

Lymphokine mediated production of an epidermal cell proliferation factor by cultured murine bone marrow cells

The effect of cultured bone marrow cell supernatant (BMS) was studied on the proliferative response of cells of the transformed murine epidermal cell line Pam 212. Elevated DNA synthesis was found in Pam 212 cells cultured with BMS from bone marrow cells grown in spleen cell conditioned medium with concanavalin A (ConA). Pam cell proliferative activity was related to the histamine content in the culture supernatant. Neither spleen cell conditioned medium with IL1, IL2, or IL3 activity, nor ConA alone, showed any effect on Pam cell growth. A soluble mediator from the cultured bone marrow cells with mast cellcharacteristics was thought to be responsible for the stimulation of Pam cell growth, and Con A appeared to be a prerequisite for generation of this factor by the bone marrow cells.