Metastatic Crohn's disease. Report of 3 cases with special reference to histopathologic findings.

BACKGROUND: Metastatic Crohn's disease is a rare, often unrecognized cutaneous disorder lacking definite histopathologic criteria. The purpose of this study was to document clinicopathologic and immunologic findings in 3 patients with metastatic Crohn's disease. The histopathologic findings are evaluated in correlation to those reported in the literature in an attempt to better define the histopathologic features. OBSERVATIONS: None of the patients showed signs of depressed cell-mediated immune response as evaluated with skin tests and T-cell subtyping of blood samples. One of the patients had antineutrophil cytoplasmic antibodies. Polymerase chain reaction, a highly efficient method of amplifying low levels of specific DNA sequences, did not show mycobacterial DNA in the samples studied. Granulomas of the sarcoid type with numerous foreign body and Langhans giant cells were the dominating features. In accordance with previous results, we found vascular involvement in 2 cases, manifested as granulomatous perivasculitis in both. We also found necrobiotic areas in all 3 cases. CONCLUSIONS: We propose that both necrobiosis and granulomatous perivasculitis be added to the histopathologic characteristics of metastatic Crohn's disease. Patients may even have a positive antineutrophil cytoplasmic antibody test result.

Antiphospholipid antibodies and anetoderma: are they associated?

BACKGROUND: Macular atrophy or anetoderma is a rare skin disease of unknown pathogenesis, characterised by wrinkled or flaccid skin. OBJECTIVE: The finding of anetoderma in 5 patients followed up because of false-positive seroreactions of syphilis prompted us to study the occurrence of antiphospholipid (aPL) antibodies in anetoderma. METHODS: 14 unselected patients with primary anetoderma (PA) were collected from hospital records and clinical, immunological and histological findings were compared in the two patient groups. RESULTS: Of the 5 patients, 3 fulfilled the criteria for antiphospholipid syndrome. In two cases, it was secondary to systemic lupus erythematosus (SLE). Of the 14 PA patients 1 had aPL antibodies and 4 had borrelia antibodies. Two patients had thyroid antibodies; 1 of them developed SLE. In several biopsy specimens, microthromboses were seen in both patient groups. CONCLUSION: On the basis of this study and our previous findings, it seems that anetoderma is more often associated with aPL-positive SLE or lupus-like disease than with aPL-negative disease. Immunological mechanisms play an important role in both primary and secondary anetoderma. The meaning of false-positive serological tests for syphilis or borrelia and aPL antibodies is not clear, but they may be reacting to some still unidentified antigen. Probably, various systemic as well as local inflammatory and non-inflammatory processes, e.g. microthromboses, can trigger anetoderma via still unknown pathomechanisms.

HLA antigens and complement C4 allotypes in patients with chronic biologically false positive (CBFP) seroreactions for syphilis: a follow-up study of SLE patients and CBFP reactors.

We report a follow-up of our previous study of HLA markers in 118 unrelated patients: 49 with definite systemic lupus erythematosus (SLE) (group 1), 32 with definite or probable SLE and chronic biologically false positive (CBFP) seroreactions for syphilis (group 2), and 37 CBFP reactors (group 3). Definite SLE was confirmed in 28 (90.3%) of the patients in group 2, equally in HLA B8- and HLA B7-positive patients. Three of the CBFP reactors developed SLE, two (40%) out of five HLA B8-positive as compared to one (6.6%) out of 15 HLA B7-positive CBFP reactors (P = 0.07). Fourteen patients died (groups 1 and 2). Eight of the 24 HLA B8-positive patients died in contrast to one of the 20 HLA B7-positive patients (P < 0.02). Of the CBFP reactors, 70.9% had complement C4 null alleles as compared to 47.9% in controls (P = 0.05) and 50% had C4A null alleles as compared to 17.8% in controls (P < 0.05). C4B null alleles were found in 28.6% (28.6% in controls, P is not significant). The null alleles for C4A were not solely in a linkage disequilibrium with the HLA B8 DR3 haplotype. CBFP reactors with C4A null alleles had a higher risk of developing SLE, lupus-like disease or symptoms such as photosensitivity, cutaneous vasculitis and/or autoantibodies than did those with no C4A null alleles (P < 0.02).

Lupus anticoagulant and the skin. A longterm follow-up study of SLE patients with special reference to histopathological findings.

Skin manifestations were described in lupus anticoagulant (LA) positive and in LA negative SLE patients. Necrotic ulcers appearing at the beginning of the disease process characterized the 33 LA positive patients. Thirteen patients had a "peripheral vascular syndrome"; small leg ulcers of livedoid vasculitis type following deep venous thromboses, in 3 patients developing into pyoderma gangrenosum like ulcers and in 2 patients into pseudo-sarcoma Kaposi. The lesions were histologically characterized by capillary angiogenesis with extravasated red blood cells, sparse inflammatory cell infiltrates and microthromboses. Three patients had ulcers clinically and histologically resembling those seen in Degos' disease. Five patients had anetoderma showing elastic tissue depletion and microthromboses histologically. A different pattern of skin changes was seen in the LA negative patients. Our findings suggest that antiphospholipid antibodies play a pathogenetic role in the described skin manifestations of LA positive SLE patients.

Depressed cutaneous cell-mediated immunity in early rheumatoid arthritis.

To study the role of cellular immunity in recent-onset rheumatoid arthritis (RA), 26 patients with early RA were examined by skin testing with seven common recall antigens. The skin test was performed before the administration of second-line antirheumatic therapy and was repeated after six months of medication. Controls included healthy individuals and patients without known immunological abnormalities or malignancies. 50% of the RA patients were classified as anergic compared to 7% of the controls. In the RA patients, depression of cell-mediated immunity was related to gender but not to disease activity. Anergic and reactive patients showed similar clinical improvement after six months of therapy. The frequency of anergy at six months was not statistically different from that before therapy. HLA-DR4 was more frequent in the reactive patient group (92%) compared with anergic patients (53%). We conclude that cell-mediated immunity is impaired in early RA but the impairment does not correlate with disease activity or with the response to treatment and does not return to normal during treatment with second-line antirheumatic drugs.

DNA skin tests in patients with definite or suspected systemic lupus erythematosus and in dermatological control patients. A long-term follow-up study.

This study presents a long-term clinical and immunological follow-up of 62 patients during 1971 and 1973, tested intradermally with DNA derived from calf thymus. The DNA skin test is positive in almost all clear-cut cases of SLE. In addition, the DNA skin test was positive in 16 patients, but the criteria for SLE were not met at the time of testing. During the follow-up, 7 out of these 16 patients developed definite SLE, 2 developed subacute cutaneous LE and 3 developed ANA-negative SLE. This suggests that a positive DNA skin test may precede the development of SLE or some of its subtypes. All our SLE patients with skin test reactivity presented cutaneous disease manifestations suggesting that similar pathogenetic mechanisms may be involved in DNA tests and natural SLE skin lesions. Because the positive DNA skin test showed correlation with ANA, anti-DNA antibodies, cryoglobulins, lupus anticoagulant and depressed C3 and C4 values, humoral factors may be partly responsible. However, DNA skin test reactivity was also positive in ANA-negative SLE, suggesting that other mechanisms may also be involved.