Abundant immunoglobulin E-positive cells in skin lesions support an allergic etiology of atopic dermatitis in the elderly.

BACKGROUND/OBJECTIVES: Atopic dermatitis (AD) in the elderly is gradually increasing in industrialized countries in association with the aging of society. We report herein four cases of elderly AD {three extrinsic [immunoglobulin (Ig)E-mediated allergy]; one intrinsic (non-IgE-allergy)} in which we investigated the presence of IgE+ cells in lesional skin. METHODS/RESULTS: Single immunohistochemical and double immunofluorescence stainings were performed for skin biopsy specimens from AD patients and non-atopic control subjects with chronic eczema. In the lesional lichenified skin of patients with extrinsic elderly AD, numerous IgE+ cells were found among inflammatory cells infiltrates in the upper dermis. Comparative analysis of single immunohistochemistry results using serial paraffin and/or frozen sections found that many IgE+ cells showed identical distributions to tryptase+ mast cells. IgE+ cells coincident with CD1a+ Langerhans cells in the epidermis were found in small numbers only in frozen sections. Double immunofluorescence staining for IgE and CD11c revealed cells coexpressing IgE and CD11c with a dendritic morphology in the papillary and upper dermis. These IgE+ mast cells and IgE+ CD11c+ cells were also found in cured normal-looking skin from a patient with extrinsic elderly AD after successful treatment. Although only a few weakly positive IgE+ cells were detected, no IgE+CD11c+ cells were found in specimens from patients with intrinsic elderly AD or non-atopic chronic eczema. CONCLUSION: IgE-mediated allergic inflammation may play an important role in the pathobiology of elderly AD, similar to other age groups of AD.

Diffuse large B-cell lymphoma associated with skin, muscle and cranial nerve involvement.

The present case, a 75-year-old man with extranodal B-cell lymphoma showed facial hemiplegia, paresthesia and cutaneous manifestations. He was initially diagnosed as having a facial paralysis of unknown etiology. One month after the original diagnosis, erythematous indurated plaques developed on his left cheek and nose. A skin biopsy from the plaque on his cheek showed dense infiltrates of large lymphocytes with irregularly shaped nuclei and prominent nucleoli in the dermis and subcutaneous tissue. The lymphocytes were positive for L26 and CD79a. A diagnosis of diffuse large B-cell lymphoma was made. A muscle biopsy from facial muscle in the area of the erythematous plaque showed massive destruction of the muscle tissues by the lymphomatous infiltrates. Furthermore, electrodiagnostic study showed peripheral cranial nerve palsies, involving the left facial and trigeminal nerves. We conclude that diffuse large B-cell lymphoma may develop symptoms such as facial hemiplegia and paresthesia prior to cutaneous manifestations. Diffuse large B-cell lymphoma must be considered as one of the important causes of palsies of cranial nerves at the peripheral level.

Clinical and histopathologic analysis of the relationship between lichen planus and chronic hepatitis C.

A prospective clinical investigation of 45 patients with lichen planus (LP) demonstrated a significant association between LP and chronic hepatitis C. Anti-hepatitis C virus (HCV) antibodies were found in 17 (37.8%) of the 45 LP patients. This was significantly higher than in the controls. This higher prevalence of anti-HCV antibodies was found equally in both male and female patients in the three types of LP; cutaneous only type, mucous only type, and both cutaneous and mucous type. Most of the patients with positive anti-HCV antibodies had abnormal values of transaminase enzymes and/or a past history of chronic hepatitis. Histological and immunohistological investigations of three cases with LP and chronic hepatitis C demonstrated some morphologic similarities between these two diseases. Histopathologic findings of both LP and chronic hepatitis C were based on a T lymphocytic infiltrate with keratinocyte or hepatocyte damage. The degrees of infiltrating cells positive to UCHL-1, MX-panB, Leu-7, and human leukocyte antigen (HLA)-DR antibodies in the chronic hepatitis C lesions seemed to be similar to those in the LP lesions. These results may support a possible relationship between LP and chronic hepatitis C and the hypothesis that LP may be associated with chronic liver diseases as a result of a cytotoxic attack on the hepatocytes.

Lichen planus and Sjögren-type sicca syndrome in a patient with chronic hepatitis C.

We report a 54-year-old Japanese male with lichen planus and Sjögren-type sicca syndrome, accompanied by the latent complication of chronic hepatitis C. The patient first showed erythematous and erosive lesions with white irregular striae in the buccal mucous membrane, and blepharitis and hyperemia of conjunctiva in his eyes. He later had two small erosions on the glans penis, and flat-topped violaceous papules on the dorsa manus and nape. A biopsy specimen of the lower lip lesion demonstrated a lichenoid tissue reaction at the basement membrane zone, and lymphocytic focal accumulations in the salivary glands. Immunohistochemical study of this specimen revealed CD45RO- (T) cells associated with the expression of HLA-DR antigens predominantly in both the lichenoid tissue reaction and the lymphocytic sialadenitis. Objective keratoconjunctivitis sicca was confirmed by the Schirmer and Rose-Bengal tests. Anti-DNA antibody was positive; however anti-SS-A, and anti-SS-B antibodies were negative. Increased levels of transaminase enzymes, TTT, ZTT, and IgG were observed in first laboratory examinations; thereafter, antihepatitis C virus (HCV) antibodies and HCV-RNA were detected. The high serum amylase level, in which salivary amylase predominated, was normalized by etretinate therapy in parallel with the clinical improvement of the oral LP lesions. Our case is considered to support the hypothesis that an etiologic association may be present among lichen planus, Sjögren's syndrome, and chronic hepatitis C.

Scaling lichenoid eruptions and Sjögren-like syndrome: manifestations of nonfatal postoperative transfusion-associated graft-versus-host disease?

We report a case of an 81-year-old woman in whom lichenoid eruptions and Sjögren-like sicca syndrome developed 45 days after cholecystectomy. During surgery, one unit (130 ml) of unirradiated packed red blood cells from a male donor was transfused. The lichenoid eruptions cleared up with exfoliation: however, sicca symptoms remained during the follow-up period of four years. Histological examinations of both skin and lip biopsy specimens were in agreement with those of graft-versus-host disease (GVHD). A Y-chromosomal body was identified in the lymphocytes in the skin lesion by staining with quinacrine dihydrochloride and in the lip lesion by a method with in situ hybridization. The findings suggest that this case demonstrated the manifestations of non-fatal transfusion-associated GVHD.

Dermatitis herpetiformis in a Japanese patient with anaplastic large cell lymphoma.

We report a 73-year-old Japanese man with dermatitis herpetiformis which developed after diagnosis of anaplastic large cell lymphoma. The patient suffered fever, sweating, shivering, and multiple enlarged cervical lymph nodes. The diagnosis of anaplastic large cell lymphoma was confirmed by the histologic features of a biopsied cervical lymph node. The patient underwent combination chemotherapy. However, one month after the initial therapy, pruritic erythematous skin lesions with peripheral vesicles appeared on his buttocks. A skin biopsy showed subepidermal blister formation associated with polymorphonuclear and mononuclear cell infiltrates. Direct immunofluorescence examination of the area adjacent to the lesion showed granular deposits of IgA at the dermoepidermal junction. While it is well-known that dermatitis herpetiformis can develop into lymphoma, there have been only a few reports of its appearance after a diagnosis of lymphoma. This case suggests that dermatitis herpetiformis may be induced by anaplastic large cell lymphoma.

Characterization of infiltrating T cells in human scalp explants from alopecia areata to SCID nude mice: possible role of the disappearance of CD8+ T lymphocytes in the process of hair regrowth.

T cells may play a role in the pathogenesis of alopecia areata (AA). We attempted to elucidate the linkage between infiltrating T cells and hair regrowth processes by grafting scalp skin from the affected region of patients with AA onto severe combined immune deficiency (SCID) nude mice. When the AA scalp was grafted into the mice, the grafts were accepted, and normal hair regrowth was observed. Before grafting, CD4+ and CD8+ T cells had infiltrated into the peribulb area. After grafting, the telogen hair shifted to anagen hair, and the CD4+ and CD8+ T cell infiltrates in the bulb area decreased in all cases. CD8+ T cells had almost disappeared from all portions of the follicles. It has been suggested that CD8+ T cells play a crucial role in the pathogenesis of AA. The absence of CD8+ T lymphocytes that responded to follicular autoantigens may induce hair regrowth in the grafted skin. In addition, the CD4+ human T cells that had infiltrated or still remained in the upper-middle portions including the bulge area accompanied the HLA-DR expression after grafting. Infiltrating or surviving T cell phenotypes and locations changed during the hair cycle in the grafts. These results indicate that the location of infiltrated T cells and their phenotypes may participate not only in hair loss but also in regrowth of hair in AA.

Transfusion-associated graft-versus-host disease: an in situ hybridization analysis of the infiltrating donor-derived cells in the cutaneous lesion.

BACKGROUND: Acute graft-versus-host disease (GVHD) can occur after a blood transfusion. OBJECTIVE: In order to elucidate the pathomechanisms responsible for transfusion-associated GVHD, infiltrating donor-derived cells in a cutaneous lesion were analyzed. METHODS: A skin sample obtained from a 69-year-old woman who developed fatal GVHD after blood transfusions from male donors was studied by performing in situ hybridization (ISH) with a Y-chromosome-specific probe. RESULTS: The cell infiltrates comprised mainly CD3+ T lymphocytes. Immunohistochemistry and ISH in combination demonstrated that 99% (182/184) of the Y-body-positive cells were CD3+. Y bodies were observed in 80% of the CD8+ cells in the epidermis and dermoepidermal junction and in 77 and 45% of the CD8+ and CD4+ cells, respectively, in the dermis. CONCLUSION: These findings suggest that both CD4+ and CD8+ cells of donor origin were involved in the development of cutaneous GVHD.

Induction of eczematous skin reaction in experimentally induced hyperplastic skin of Balb/C mice by monoclonal anti-DNP IgE antibody: possible implications for skin lesion formation in atopic dermatitis.

Biphasic skin reaction with peak response at 1 and 24 h with prominent mast cell degranulation was induced by intravenous application of a monoclonal anti-DNP IgE antibody and subsequent skin test. This reaction was hapten-specific and mast-cell-dependent because no reaction was observed when oxasolone was used as an elicitation antigen or skin test was elicited in genetically mast-cell-deficient mice (W/Wvv). A partial spongiotic reaction and mononuclear cell infiltration into the epidermis were observed in mice with hyperplastic epidermis induced by topical retinoic acid. Cotransfer of DNFB-sensitized lymph node cells with anti-DNP IgE antibodies failed to enhance the skin test reaction in unsensitized mice. These results suggest that, to some degree, IgE antibody may play some role in the development of eczematous skin lesions in the rodent system without the involvement of cellular hypersensitivity.

[Six cases of Sjögren's syndrome with lichen mucosae--studies on the histopathology of salivary gland and clinical manifestation of sicca features in the patients with lichen mucosae].

A case of a 54-year old man with lichen mucosae and Sjögren's syndrome was reported. Clinical and histopathological analysis was made on the presence of sicca features in 6 patients with lichen mucosae. All patients complained either xerophthalmia or xerostomia and 5 out of 6 cases showed specific lymphocytic foci seen in Sjögren's syndrome in addition to lichenoid tissue reaction in the specimen obtained from buccal mucosae. Objective keratoconjunctivitis sicca was demonstrated in 3 cases. Immunologically, abnormal laboratory findings were observed in 5 cases (4 cases with a positive ANA and 3 cases with a positive anti microsome antibody). These findings suggest that lichen mucosae might develop in a close association with Sjögren's syndrome and relationship between these two disease was discussed in this article.