Mast Cells Are Activated in the Giant Earlobe Keloids: A Case Series.

Mast cells and inflammatory cells are abundant in keloid and hypertrophic scar tissues. Even if the cause of physical injury is similar, such as piercing or scratching with hands, clinical findings show differences in the size of keloids in the same area. Hence, we performed histological studies on giant keloids larger than the earlobe, and other smaller keloids. We also examined the risk factors associated with the formation of giant lesions. No statistically significant differences in the association of the risk factors were observed. However, histological observations clearly showed a high number of degranulated or active mast cells with a trend towards a greater number of degranulated mast cells in the giant keloid tissues. Collagen production also tended to increase. Two patients with giant keloids were severely obese, suggesting that the persistent inflammatory state of obesity may also be involved in the growth of keloid lesions.

Trichoblastic infundibular cyst should be renamed infundibular cyst with unique papillary projections.

Trichoblastic infundibular cyst (TBIC) was previously reported as a unique keratinous cystic lesion, which was characterized by the papillary projections of follicular germinative-like cells emanating from the cyst wall. Here, we report three additional cases of this cyst and discuss the pathogenesis of this unique entity. In all cases, a unilocular cyst contained keratin, and the cyst wall was composed of squamous epithelium. A number of cords and papillary projections emanated from the basal layer of the cyst wall. They were composed of cells with large nuclei and scant cytoplasm arranged in a peripheral palisade. Immunohistochemically, anti-cytokeratin 15, anti-cytokeratin 20, and anti-epithelial cell adhesion molecule antibodies were negative. Thus, these cells resembled follicular germinative cells or sebaceous mantle morphologically, but we failed to prove the differentiation immunohistochemically. The cyst was surrounded by fibrotic stroma and inflammatory cells, suggesting previous rupture of the cyst. We speculate that the cells of the projections possibly differentiate into the mantle rather than follicular germinative cells, even though we could not provide sufficient immunohistochemical evidence. We also suggest that they may be induced by special reaction to fibrohistiocytic stroma surrounding the infundibular cyst. Therefore, TBIC should be renamed infundibular cyst with unique papillary projections.

Case of Rapid Progression of Hemiatrophy on the Face: A New Clinical Entity?

A lot of diseases, including lupus profundus, morphea, lipodystrophy, and Parry-Romberg syndrome, may manifest progressive hemifacial atrophy. These diseases usually progress slowly and rapid progression of atrophy is extremely rare. We report a case of elderly-onset rapid progression of hemifacial atrophy only in three weeks. Our case did not meet variable differential diagnoses. We discuss the clinical character of the patient against the past of literature and suppose it may be a new clinical entity.

False-positive serology following intravenous immunoglobulin and plasma exchange through transfusion of fresh frozen plasma in a patient with pemphigus vulgaris.

Intravenous immunoglobulin therapy and plasma exchange through transfusion of fresh frozen plasma are therapeutic options for patients with refractory pemphigus vulgaris. Passive acquisition of various clinically important antibodies through these therapies can occur, leading to false serology and negatively affecting patients' clinical care. It is recommended that dermatologists recognize the possibility of these phenomena and interpret them appropriately. Here, we report false-positive serology following intravenous immunoglobulin therapy and plasma exchange through transfusion of fresh frozen plasma in a patient with refractory pemphigus vulgaris. We also discuss the measure for misinterpretation and unnecessary clinical intervention.

Antigen-independent development of Foxp3+ regulatory T cells suppressing autoantibody production in experimental pemphigus vulgaris.

The CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) play suppressive roles in various types of autoimmunity. It has been reported that Tregs develop in the thymus after high-affinity interaction of their TCR with self-peptide/MHC ligands mostly utilizing TCR-transgenic system. In this study, we examined whether the specific antigen is involved in the development of polyclonal Tregs in pemphigus vulgaris (PV), an autoimmune blistering disease caused by anti-desmoglein 3 (Dsg3) IgG antibodies, as a model system. Adoptive transfer of splenocytes of Dsg3(-)(/-) mice immunized with recombinant mouse Dsg3 to Rag2(-)(/-) recipient mice expressing Dsg3 resulted in the stable production of anti-Dsg3 IgG and the development of PV phenotypes. We show here that Tregs control anti-Dsg3 antibody production in PV model mice: the adoptive transfer of Tregs and the depletion of endogenous Tregs suppressed and augmented, respectively, the anti-Dsg3 antibody production. To examine whether the endogenous expression of Dsg3 is involved in the generation of these PV-relevant Tregs, we compared the potential of wild-type Tregs with that of Tregs from Dsg3(-)(/-) mice. Polyclonal Tregs from Dsg3(-)(/-) mice were more potent than that of wild-type mice, in both adoptive transfer and Treg-depletion experiments, while suppressive activities against IgG production against an irrelevant antigen were similar between Tregs from wild-type and Dsg3(-)(/-) mice. Our observation implies that Tregs capable of suppressing T(h) cells that drive autoantibody production can develop in the absence of the target antigen.

Immune dysregulation of pemphigus in humans and mice.

Pemphigus vulgaris is an autoimmune blistering disease of the skin and mucous membranes that is caused by immunoglobulin (Ig)G autoantibodies against the cadherin-type adhesion molecule desmoglein (Dsg)3 expressed on stratified epithelial cells. Interaction between antigen-specific T and B cells, which is selectively achieved through T-cell receptor/major histocompatibility complex-peptide complex association and subsequently corroborated by co-stimulatory molecules such as CD40/CD154, is required for production of pathological anti-desmoglein 3 antibody. Some genetically and environmentally susceptible individuals harbor desmoglein reactive B and T cells, and anti-desmoglein antibodies were detected in their serum. Analysis of the anti-desmoglein antibody clones derived from pemphigus patients or pemphigus model mice revealed that pathogenic antibodies mostly react with conformational epitopes on mature form desmogleins, whereas non-pathogenic ones tend to react with non-conformational epitopes. Surprisingly, antibodies to the Dsg1 precursor pro-protein are also cloned from individuals without pemphigus. These observations suggest that active suppression by regulatory cell subsets is dominant in these susceptible individuals. In fact, Dsg-reactive T-inducible regulatory type 1 (Tr1) cells are readily detected in healthy carriers of pemphigus-related human leukocyte antigen haplotypes, but rarely in pemphigus patients. These Tr1 cells can be functionally converted to T-helper 2-like cells which secrete interleukin-2 by inactivation of Foxp3 through antisense oligonucleotides. Thus, delicate balance between self-reactive lymphocytes and regulatory T cells may be a key element in determining whether individuals produce pathogenic antibodies and develop pemphigus phenotypes or not.