Follicular Infiltration Research Articles

Vaccination-induced cutaneous pseudolymphoma

Although mild early cutaneous transient reactions to vaccinations are common, late-onset chronic lesions have been scarcely reported. We report herein a series of 9 patients presenting with cutaneous and subcutaneous pseudolymphoma. Nine patients presenting with late-onset, chronic skin lesions occurring at the site of antihepatitis B (8 cases) and antihepatitis A (one case) vaccination were reported. Histopathologic and immunohistochemic studies, and molecular analysis of clonality of skin biopsy specimens, were performed. Furthermore, the presence of vaccine products was investigated in skin lesions by using histochemical, microanalytic, and electronic microscopy techniques. Histopathologic studies showed dermal and hypodermal lymphocytic follicular infiltrates with germinal center formation. The center of follicles was mostly composed of B cells without atypia, whereas CD4+ T cells were predominant at the periphery. Molecular analysis of clonality revealed a polyclonal pattern of B-cell and T-cell subsets. Aluminium deposits were evidenced in all cases by using histochemical staining in all cases, and by microanalysis and ultrastructural studies in one case. Associated manifestations were vitiligo (one case) and chronic fatigue with myalgia (two cases). Cutaneous lymphoid hyperplasia is a potential adverse effect of vaccinations including aluminium hydroxide as an adjuvant. Further prospective studies are warranted to evaluate the incidence of this complication in the immunized population.

Follicular Mycosis Fungoides: Variability of a Rare Entity

Three patients with follicular mycosis fungoides (FMF), a rare variant of folliculotropic cutaneous T-cell lymphoma, are discussed. Follicular involvement in cutaneous T-cell lymphoma commonly presents clinically with alopecia, follicular cysts, or comedo-like lesions usually associated with follicular mucinosis and strong epidermotropism. In contrast, FMF, in a strict sense, has been defined as a lymphocytic infiltration of hair follicles in the absence of both epidermal invasion and follicular mucin. Case 1 shows a clinically stable form of FMF characterized by circumscribed alopecia and its persistent resistance to topical therapeutic approaches. In contrast, Cases 2 and 3 demonstrate that classic mycosis fungoides lesions and FMF can occur simultaneously and that transitions occur from mycosis fungoides to FMF and vice versa. These observations strengthen the concept that FMF and mycosis fungoides represent just two variants of one entity of cutaneous T-cell lymphoma. In Case 3, rapid progression into tumor-stage mycosis fungoides and the follicular infiltration was controlled with bexarotene. Because it was previously suggested that FMF may have a worse prognosis compared with classic mycosis fungoides, this impressive response to bexarotene is of great clinical interest and may spark new studies employing this novel retinoid for FMF treatment.

Expression of the B cell-attracting chemokine CXCL13 in the target organ and autoantibody production in ectopic lymphoid tissue in the chronic inflammatory disease Sjögren's syndrome.

Sjögren's syndrome is an autoimmune disease characterized by lymphocytic infiltrates resembling secondary lymphoid organs in salivary glands. In this study, we demonstrate the expression of the lymphoid tissue homing chemokine CXCL13 (BCA-1/BLC), which has attracting properties for B cells and subsets of activated T cells, in salivary glands of patients with Sjögren's syndrome using immunohistochemistry and in situ hybridization. CXCL13 expression was primarily observed in epithelial cells in acini and ducts of inflamed glands while its receptor, CXCR5 (BLR-1), was expressed on the infiltrating mononuclear cells. In addition, cells producing antibodies against one of the major autoantigens in Sjögren's syndrome, Ro 52, were identified at the periphery of the follicular infiltrates indicating that the ectopic lymphoid tissue is directly involved in the disease process. Identification of CXCL13 and CXCR5 in salivary glands suggests that the target organ plays an essential role in the inflammatory process by recruiting B and T cells. These results also provide a molecular mechanism by which lymphoid neogenesis and ectopic germinal centre formation might occur in the glands of these patients, which may be the key step in the development of the chronic inflammatory process in Sjögren's syndrome.

The histologic value of adnexal (eccrine gland and follicle) infiltration in mycosis fungoides.

To verify the incidence and the possible diagnostic use of detecting adnexotropism in mycosis fungoides (MF). We reviewed the frequency and the intensity of the eccrine and follicular infiltration in 104 biopsy specimens from indisputable cases of MF and in a control group of 20 biopsy specimens of spongiotic dermatitis. Syringohyperplasia and follicular mucinosis were also evaluated. A prominent eccrine infiltration was noted in 32 of 104 specimens (30%). Marked acrosyringial and ductal eccrine hyperplasia was present in 5 specimens (5%). In 13 of the 32 specimens with prominent eccrine infiltration (40%), epidermotropism was slight or less evident than syringotropism. Follicular structures were visible in 59 specimens and significantly infiltrated in 57%. Follicular mucinosis was found in 5 (8.4%). In the control group of spongiotic dermatitis, a significant eccrine and follicular infiltration was found only in case (5%). Adnexal (eccrine gland and follicle) infiltration may be a useful diagnostic tool in MF, particularly in those in which epidermotropism is slight.

MRL-lpr/lpr mice exhibit a defect in maintaining developmental arrest and follicular exclusion of anti-double-stranded DNA B cells.

A hallmark of systemic lupus erythematosus and the MRL murine model for lupus is the presence of anti-double-stranded (ds)DNA antibodies (Abs). To identify the steps leading to the production of these Abs in autoimmune mice, we have compared the phenotype and localization of anti-dsDNA B cells in autoimmune (MRL+/+ and lpr/lpr) mice with that in nonautoimmune (BALB/c) mice. Anti-dsDNA B cells are actively regulated in BALB/c mice as indicated by their developmental arrest and accumulation at the T-B interface of the splenic follicle. In the MRL genetic background, anti-dsDNA B cells are no longer developmentally arrested, suggesting an intrinsic B cell defect conferred by MRL background genes. With intact Fas, they continue to exhibit follicular exclusion; however, in the presence of the lpr/lpr mutation, anti-dsDNA B cells are now present in the follicle. Coincident with the altered localization of anti-dsDNA B cells is a follicular infiltration of CD4 T cells. Together, these data suggest that MRL mice are defective in maintaining the developmental arrest of autoreactive B cells and indicate a role for Fas in restricting entry into the follicle.

Neutrophilic Follicular Infiltrates May Reflect Systemic Disease

In most cases showing neutrophilic infiltrates in the region of partially destroyed hair follicle epithelium, a diagnosis of bacterial or fungal

Eosinophilic pustular folliculitis effectively treated with recombinant interferon-γ: suppression of mRNA expression of interleukin 5 in peripheral blood mononuclear cells

Eosinophilic pustular folliculitis (EPF) is characterized clinically by pruritic grouped follicular papules and pustules on the trunk, limbs, and face, and, histologically, by follicular infiltration with eosinophils. The blood eosinophil count is elevated in most patients. Oral minocycline, nonsteroidal anti-inflammatory drugs, diaminodiphenylsulphone, and corticosteroids may induce remission. We report two Japanese men with EPF who responded poorly to the usual therapy. Intravenous injections of recombinant interferon-gamma (rIFN-gamma), 5 x 10(5) to 2 x 10(6) Japan Reference Unit (JRU) (1 JRU roughly corresponds to 4 NIH units) daily for 7 days, cleared the skin lesions and returned the peripheral eosinophil counts to normal in both patients. However, the lesions recurred 2-3 days after rIFN-gamma was stopped. Both patients have received intravenous rIFN-gamma once or twice a week for nearly 1 year without systemic side-effects. Reverse transcriptase-polymerase chain reaction revealed a decreased expression of interleukin 5 (IL-5) mRNA in peripheral mononuclear cells after the rIFN-gamma therapy. rIFN-gamma may become the treatment of choice in recalcitrant EPF, although further studies are needed. It may work by interfering with the immunological function of type 2 T-helper cells, including IL-5 production responsible for the growth and differentiation of eosinophils.

The DEBR rat, alopecia areata and autoantibodies to the hair follicle

Many attempts have been made to implicate hair follicle-specific autoantibodies in the pathogenesis of alopecia areata (AA), a suspected autoimmune disease. Using the DEBR rat model for AA, we developed a refined indirect immunofluorescent technique to examine the sera from individual rats for the presence of autoantibodies to the hair follicle and to other tissues. Sera were tested on cryostat sections from normal PVG/Ola rats and DEBR rats. We found that DEBR sera contained IgG autoantibodies specific for hair follicle epidermal differentia. While individual sera revealed detailed differences, the target tissues identified were hair cortex and cuticle and the inner root sheath, especially the Henle's layer. Some sera also contained autoantibodies specific for skeletal muscle and nuclear components. Of 10 young prelesional rats with apparently normal coats of hair, three had hair follicle autoantibodies and seven had skeletal muscle autoantibodies. Nine of 10 active lesional rats with progressing hair loss had follicle autoantibodies and four had skeletal muscle autoantibodies. All 10 established lesional rats had follicle autoantibodies and one had muscle autoantibodies. Control sera from eight PVG/Ola rats showed no specific positive staining for hair follicle components or other tissues. Autoantibodies to intracellular hair follicle differentiation products were readily detected in DEBR rat sera. As these antibodies appeared to be generated after the appearance of the mononuclear follicular infiltrate, such autoantibodies may be a secondary effect. We conclude that, while the presence of autoantibodies in the DEBR rat model is associated with autoimmune activity, their role in the pathogenic progression of AA has yet to be ascertained.

Characterization of feline Helicobacter pylori strains and associated gastritis in a colony of domestic cats.

Twenty-four young adult domestic cats from a commercial vendor were found to be infected with Helicobacter pylori. Histopathologic analyses, selected electron microscopy, and urease mapping were performed on mucosal samples collected from the cardias and fundi, bodies, and antra of these cats' stomachs. H. pylori organisms were abundant in all areas of the stomach on the basis of histologic evaluation and urease mapping. H. pylori infection was associated with a moderate to severe lymphofollicular gastritis in 21 of 24 cats (88%). The gastritis was most pronounced in the antral region and consisted mainly of multifocal lymphoplasmacytic follicular infiltrates in the deep mucosa. The severity of gastritis in the antrum corresponded to high numbers of H. pylori there on the basis of the use of the urease assay as an indicator of H. pylori colonization. Ten of 24 cats (42%) also had small to moderate numbers of eosinophils in the gastric mucosa. All 24 cats had gastric lymphoid follicles, with follicles being most prevalent in the antrum. Electron microscopy of gastric tissue revealed numerous H. pylori organisms, some of which were closely adhered to the mucosal epithelium. Human H. pylori gene-specific primers to ureA and ureB amplified products of similar sizes from H. pylori cat isolates. Digestion of the products with restriction enzymes resulted in fragments characteristic of the restriction fragment length polymorphism patterns of H. pylori isolates from humans. In the domestic cat, H. pylori infection is associated with a lymphofollicular gastritis, consisting of lymphocytic and plasmacytic infiltration into the lamina propria, and the organism appears to provide chronic antigenic stimulation resulting in the formation of gastric lymphoid follicles.

Eosinophilic Pustular Folliculitis (Ofuji's Disease)

Eosinophilic pustular folliculitis is a distinctive dermatosis that was first described in Japan. Although the histopathologic feature of eosinophilic pustular folliculitis is characterized by follicular infiltrates with numerous eosinophils, its pathophysiology remains unclear. The lesional skin of five patients with eosinophilic pustular folliculitis was examined using several monoclonal antibodies including a variety of anti-leukocyte adhesion molecules: endothelial cell adhesion molecule 1, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1, by means of immunohistochemical techniques. Intercellular adhesion molecule 1 expression by keratinocytes was observed on follicular epithelium, but not on epidermis. The migration of eosinophils and lymphocytes, which were intensely positive for antilymphocyte function-associated antigen 1, was limited to follicular epithelium. Endothelial cell adhesion molecule 1 and vascular cell adhesion molecule 1 expression of vascular endothelium was more often observed around hair follicles. There was no reactivity for interleukin 8 in follicular epithelium. These findings may explain the selective migration of eosinophils and lymphocytes to the hair follicles in eosinophilic pustular folliculitis.

Cytotoxic folliculitis in GvHD

Recent observations indicate that stem cells of the murine hair follicle exist exclusively as a subpopulation of relatively undifferentiated outer root sheath cells located in the bulge region at the mid-portion of the follicle. Because it has been hypothesized that stem cells of interfollicular epidermis may represent targets of cytotoxic responses in acute graft-versus-host disease (AGVHD), we studied murine AGVHD and observed sequential skin biopsies for the presence and evolutionary pattern of follicular injury. Highly purified subsets of donor T cells were used to produce AGVHD to multiple minor histocompatibility (H) antigens in two strain combinations of mice matched for the major histocompatibility complex (MHC). In the C3H.SW- greater than B6 strain combination, only CD8+ effector cells produced histologic evidence in skin of AGVHD, which peaked three weeks post-transplant. In the B10.D2- greater than DBA/2 strain combination, CD4+ effector cells, and to a lesser extent, CD8+ cells, mediated disease, which peaked during the fourth week post-transplant. Analysis of skin from both strain/effector cell combinations revealed follicular infiltrates preferentially involving follicular stem cell (FSC) regions (bulge) of anagen follicles between the second and third weeks post-transplant. These infiltrates often preceded infiltration of adjacent interfollicular epidermis and were associated with follicular involution to telogen (resting) phase. By the fourth week post-transplant, greater than 50% of follicles were in telogen phase and residual inflammation was minimal. This provided a unique opportunity to observe follicular recovery from telogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Protective effect of OK‐432 (streptococcal preparation) on murine fulminant hepatitis following mouse hepatitis virus infection

The effects of OK‐432 (streptococcal preparation) on murine fulminant hepatitis were investigated. Hepatitis was induced by injection of mouse hepatitis virus type 2 (MHV‐2) at a strength of either 1 times 103 or 1 times 104 plaque‐forming units (PFU). Mice without OK‐432 treatment died within 5 days, whereas mice pre‐inoculated with OK‐432 showed survival rates of 50% (1 times 103PFU) or 10% (1 times 104PFU) after 60 days. Survival time was not prolonged if OK‐432 was injected after MHV‐2. Examined histologically, mice not treated with OK‐432 showed severe haemorrhagic necrosis of the liver, often panlobular. Treated mice showed less necrosis; the least necrosis was observed in those injected with OK‐432 before MHV‐2. In those mice injected first with OK‐432 and then with 1 times 103PFU of MHV‐2 that survived 7 days, autopsy showed a very slight and focal hepatic necrosis, with follicular infiltration by lymphocytes and macrophages. Mitogenic reaction of spleen cells was remarkably less than normal in mice with MHV‐2 injection. However, mice injected with OK‐432 before MHV‐2 (same treatment as mice showing high survival rates) showed relatively high reactivity in comparison with mice not treated with OK‐432.