A Case of Multicentric Reticulohistiocytosis,Systemic Sclerosis and Sjögren Syndrome

We report the case of a 42-year-old Japanese woman who developed multicentric reticulohistiocytosis (MR) complicated by systemic sclerosis (SSc) and Sjögren syndrome (SS). The patient complained of tender nodules on the left hand, polyarthralgia in the finger joints and knees, and xerostomia. The skin nodules were distributed mainly on her hands and fingers with skin sclerosis. The serum anti-nuclear test revealed anti-centromere antibody and the discrete speckled pattern of anti-nuclear antibody. The biopsy specimens from the finger nodule and the sclerotic finger skin showed a perivascular infiltration of multinucleated giant cells with ground-glass cytoplasm and dermal thick collagen proliferation, respectively. The lip biopsy and sialography specimens showed periductal lymphocyte infiltration and apple tree-like changes. Systemic corticosteroid treatment improved the polyarthritis, xerostomia, and skin sclerosis rapidly but suppressed the nodular lesions only gradually. This is the first report of a combined case of MR, SSc and SS. This multiple autoimmune complication suggests the involvement of an immunological disturbance in the pathogenesis of MR.     

Clinical Analysis of Recurrent Hypergammaglobulinemic Purpura Associated with Sjögren Syndrome

Recurrent purpuric lesions are occasionally seen in patients with Sjögren syndrome. Hypergammaglobulinemia is one of the underlying precipitating factors of this condition. Clinical and histopathological analyses were performed on 5 cases of hypergammaglobulinemic purpura associated with Sjögren's syndrome, and the effects of immunomodulatory therapy were evaluated with regards to these conditions. Three out of 5 cases were successfully treated with oral gold compound (Auranofin) and one case with a low dose of cyclophosphamide. Episodic purpura subsided two months after initiation of therapy with improved serum IgG levels. Salivary flow and serum amylase levels also improved in some cases. Immunomodulatory therapy may be useful in managing recurrent purpura based on hypergammaglobulinemia associated with Sjögren syndrome.     

Clinical and Histological Analysis of Labial Lip Biopsy in Sjögren Syndrome

Labial lip biopsy findings from 52 patients with Sjögren syndrome (SjS) and cutaneous manifestations were clinically analyzed. Findings of the labial lip biopsy with more than one focus (a cluster of at least 50 lymphocytes) were positive in 52% (28/52). Sixteen patients who presented with oral dryness had negative labial lip biopsy findings with less than one focus score and five patients without oral dryness had positive results. Cells infiltrating into the salivary gland were categorized as plasma cell rich (Group 1), lymphocyte rich (Group 3), intermediate (Group 2), or no gland in biopsied specimens (Group 4). Sicca complaint and the grade of lip biopsy score were significantly higher in Group 3 than in Group 1; no differences were observed in laboratory findings between Groups 1 and 3. The patterns of age distribution and salivary flow rate were also not statistically significant in these two groups. The patients with plasma cell rich infiltrate presented oral dryness, although their clinical and grade of lip biopsy scores were relatively low; most of these patients have secondary SjS. Some of the patients in Group 4 showed an advanced stage of the disease though their lip biopsy score was grade 1 with atrophic or no gland. These data suggest that labial lip biopsy is a useful screening method for the diagnosis of Sjögren syndrome and that clinical manifestations may differ in parallel with the type of infiltrating cell.     

Lymphocyte Response to Staphylococcal Enterotoxin B in Patients with Annular Erythema Associated with Sjögren Syndrome

Lymphocyte response to staphylococcal enterotoxin B (SEB) was analysed in 11 cases with Sjögren syndrome (SjS) who developed annular erythema during the course. Increased lymphocyte response against SEB was observed on day 5 in those patients who developed annular erythema at the time of examination. A similar reaction pattern was observed when Con A and PWM, but not protein A, were used as the mitogen. No significant lymphocyte response was observed in the patients in the inactive stage without annular erythema or in normal controls. Furthermore, peripheral blood lymphocytes express LFA-1 after SEB stimulation. These results suggest that lymphocytes from SjS patients react to various types of antigenic or mitogenic stimulation and that they express cell adhesion molecules, especially in patients with active annular erythema.     

Asymptomatic Primary Sjögren's Syndrome in a Patient with Penicillin Drug Eruption

A 20-year-old woman visited our clinic because of acral numbness and skin eruptions after administration of oral penicillin. Serological tests revealed an increase of immunoglobulins (G & M), positive rheumatoid factor, anti-nuclear factor, anti-SSA and -SSB antibodies. Ophthalmologic and otolaryngological studies were consistent with those of Sjögren's syndrome. However, a skin biopsy specimen failed to show any specific changes for Sjögren's syndrome and the diagnosis of penicillin drug eruption was considered to be more preferable. We briefly discussed the coexistence of a drug allergy and asymptomatic connective tissue disease.     

ICAM-1 and LFA-1 Expressions in the Lesional Skin of Annular Erythema Associated with Sjögren Syndrome

ICAM-1 and LFA-1 expression was studied in the lesional skin of ten cases of annular erythema associated with Sjögren syndrome. Most of the infiltrating mononuclear cells around blood vessels expressed LFA-1 in addition to its strong expression on vascular endothelial cells and focal expression on the epidermal basal cell layer in 3 cases. ICAM-1 expression on vascular endothelial cells was similar to LFA-1, although relatively focal and weak expression was observed on mononuclear cells. ICAM-1 expression on keratinocytes was focal and limited to the basal cell layer in annular erythema. These findings suggest that strong expression of ICAM-1 on endothelial cells but not keratinocytes and LFA-1 on mononuclear cells might play some role in the induction of skin lesions in annular erythema associated with Sjögren syndrome.     

Primary Sjögren's Syndrome and Psoriasis Vulgaris in a Case of OKT4 Epitope Deficiency

We report a 29-year-old female OKT4 epitope deficiency patient with primary Sjögren's syndrome and psoriasis vulgaris. Immunological investigations during the prolonged clinical course of her herpes zoster revealed that she has OKT4 epitope deficiency and primary Sjögren's syndrome. She had been treated for psoriasis vulgaris for 17 years without systemic immunosuppressive therapy. Flow cytometric study revealed that her OKT4 deficiency is heterogeneous and excluded interference with the OKT4 epitope by anti OKT4 autoantibodies. The rare coexistence of primary Sjögren's syndrome and psoriasis implicates an immune disturbance due to an unusual phenotype of CD4.     

Spongiotic Annular Erythema in SS-A/SS-B Antibody Negative Sjögren's Syndrome

We reported four cases of Sjögren's syndrome (SjS) who manifested a new type of annular erythema that differs from the previously described annular erythema seen in anti-SS-A/SS-B antibody positive SjS in both clinical and histological findings. Characteristic histological features are the presence of spongiotic changes around the acrosyringium and perivascular lymphocytic infiltration without liquefaction degeneration or epidermal change, suggesting lupus erythematosus. No complement or immunoglobulin depositions are demonstrated along the basement membrane zone or around blood vessels. Clinically, this type of erythema usually appears on the trunk or extremities with itchy sensations, especially in summer, which contrasts with the preferential occurrence of the previously reported SjS related annular erythema on the facial skin in winter. Immunologically, all four cases lacked anti-SS-A and anti-SS-B antibodies, but possessed positive anti-microsome antibodies or thyroid tests. In three cases, metal allergy was demonstrated by patch test, which might suggest that the sweat duct is the primary target of excreted metals in this condition and that underlying SjS might play some role in the higher prevalence of metal allergy or in induction of sweat duct injury, similar to the interstitial nephritis which is now thought to be an exocrine manifestation of SjS.     

Recurrent Annular Erythema in a Case of Seronegative Sjögren's Syndrome

We describe a case of Sjögren's syndrome who repeatedly developed annular erythema on her extremities. Her anti-nuclear antibody, anti-SSA/Ro antibody, and anti-SSB/La antibody were all negative. Characteristics of the annular erythema included a tendency to appear on the extremities especially in summer, spontaneous regression after 1–2 weeks, and residual slight pigmentation. The histological findings revealed dermal perivascular lymphocytic infiltration admixed with some neutrophils. Slight exsudative changes were found in the upper dermis. There were no epidermal changes. This case suggests the existence of annular erythema which may not be related to the anti-SSA/Ro or anti-SSB/La antibody. Unknown factors other than those antibodies may be involved in the pathogenesis of the annular erythema.     

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, anti-hepatitis 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.     

Primary Sjögren's Syndrome Followed by Chronic Myelogenous Leukemia: A Case Report with a Ten Year History

We describe a female patient with primary Sjögren's syndrome who subsequently developed chronic myelogenous leukemia. The patient received a bone marrow transplant (BMT) from a genotypically HLA-identical brother after pre-transplant preparation with busulfan and cyclophosphamide. Eighteen weeks later, cutaneous and mucosal chronic graft-versus-host disease developed, followed by death 11 months after transplantation. Anti-Ro/SS-A antibodies disappeared within 6 months post-BMT, but antinuclear antibodies remained positive through the post-transplant course.     

Acral Ichthyosiform Mucinosis in Association with Sjögren's Syndrome: A Peculiar Form of Pretibial Myxedema?

Two Japanese women developed well-dermarcated ichthyosiform plaques on the lateral aspect of their lower legs. Deposition of mucin was demonstrated throughout the papillary dermis, unlike the site of mucin deposition seen in pretibial myxedema. Their thyroid function was normal. The condition of both women was complicated by Sjögren's syndrome. One of them who presented with positive anti-microsomal and anti-thyroglobulin antibodies had goiter, suggesting that her malady was also complicated by Hashimoto's thyroiditis. Their skin manifestations differed from those described in cutaneous mucinosis including pretibial myxedema, specifically with regard to the well-demarcated ichthyosiform appearance, the mucin deposition in the papillary dermis, and the association with Sjögren's syndrome. To the best of our knowledge, our cases may thus be considered to be a previously undescribed form of cutaneous mucinosis associated with Sjögren's syndrome.     

Hypergammaglobulinemic Purpura Associated with Sjögren's Syndrome and Chronic C Type Hepatitis

Although hypergammaglobulinemic purpura usually occurs secondarily on the lower legs in several disorders, purpura has also recently been reported to be associated with chronic C type hepatitis (HCV). To define the differences in the clinical, histological and laboratory findings and the prognosis of hypergammaglobulinemic purpura associated with those two disorders, we examined ten patients with hypergammaglobulinemic purpura, 6 patients with hypergammaglobulinemic purpura associated with Sjögren's syndrome (SjS) and 4 patients with hypergammaglobulinemic purpura with chronic C type hepatitis. Five of 6 patients with SjS were female. Attacks of purpura occurred in the pretibial area in all cases. Triggering factors included long walks and prolonged standing. The mean duration of attacks was 6.4 days. No systemic manifestations were associated. Anti-Ro/SS-A and anti-La/SS-B antibodies were expressed in one case. Spontaneous regression was noted in all cases; however, recurrence was noted in one. On the other hand, all the 4 patients with hypergammaglobulinemic purpura associated with HCV were men. Purpura was indurated in a few cases. Involved sites included the knee, forearm, abdomen and thigh in addition to the lower leg. The mean duration of attacks was 12.6 days. Recurrent purpura was noted in one case. Cryoglobulin was positive in three cases. In one patient with severe recurrent purpura, attacks stopped with prednisolone 10 mg/day. Histologically, leukocytoclastic vasculitis was detected in three cases associated with SjS and two cases with HCV. In conclusion, hypergammaglobulinemic purpura associated with HCV appears to occur unilaterally with a sex predilection for men and the manifestations last longer than those associated with SjS. Severe palpable purpura was also noted in association with HCV; systemic prednisolone resulted in good control.     

Postmenopausal frontal fibrosing alopecia in a Japanese woman with Sjögren's syndrome

Postmenopausal frontal fibrosing alopecia (PFFA) is a rare alopecia that develops in the frontoparietal scalp of postmenopausal women. Etiology of PFFA is unknown. Most of cases of PFFA have been reported in European and North American countries. Herein, we report a Japanese case of PFFA associated with Sjögren's syndrome. A 66‐year‐old woman had had slowly progressive, band‐like, scarring alopecia on her frontoparietal scalp. Hair follicles on the margin showed follicular keratosis. Histologically, fibrosis and lymphocytic infiltration were mild. This case suggests that PFFA may show mild inflammatory reaction and mild fibrosis in Japanese women. The association with immunological disorders including Sjögren's syndrome should be studied further.     

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.     

Interstitial type granuloma annulare associated with Sjögren’s syndrome

We describe a case of granuloma annulare (GA) associated with Sjögren’s syndrome (SS) in a 69‐year‐old woman. She complained of erythematous plaques on the left forearm and neck in addition to dry eyes and mouth. The laboratory and clinical findings also fulfilled the criteria for diagnosis of SS. Histopathological examination revealed the features of interstitial type GA. It is not rare that granulomatous diseases are associated with autoimmune diseases. This case indicated that granulomatous diseases and SS are closely related and that GA should be recognized as a cutaneous manifestation associated with autoimmune diseases, including SS.     

Lupus miliaris disseminatum faciei in a patient with systemic lupus erythematosus and Sjögren’s syndrome

We herein report a rare case of lupus miliaris disseminatus faciei on the chin and neck in a patient with systemic lupus erythematosus and Sjögren’s syndrome. Histopathological features showed focal aggregates of epithelioid granulomas accompanied by mononuclear cell infiltration in the upper dermis. Immunohistological examination showed enhanced expression of CD68 and CD163. Recent findings have implicated a key role of innate immunity in the pathogenesis of systemic lupus erythematosus, and alteration in M1 and M2 macrophage profile has been suggested. Increased expression of CD163 in the affected skin and other organs, and elevated serum levels of soluble CD163, are reported in systemic lupus erythematosus. Our results may suggest that activated M2 macrophages participated in the induction of lupus miliaris disseminatus faciei in a patient with systemic lupus erythematosus and Sjögren’s syndrome.