Dermatitis herpetiformis: an evaluation of diagnostic criteria

Forty-two patients in whom a clinical diagnosis of dermatitis herpetiformis (DH) had been, made, were studied. All patients had a small intestinal biopsy, a biopsy of uninvolved skin for detection of the presence of IgA deposits by immunofluorescence, serum and red cell folate estimations and examination of the serum for anti-reticulin antibody. The response of the skin eruption to dapsone was noted. Thirty patients had biopsies of skin lesions for routine histological examination. IgA deposits were found in the uninvolved skin of thirty-five of the forty-two patients. Evidence of an enteropathy was found in thirty-four of those thirty-five patients. Of the seven patients who did not have IgA in the uninvolved skin, only one showed evidence of enteropathy, which was slight, and this patient was shown subsequently to have pemphigus and not DH. Of the thirty biopsies of skin lesions, only five showed all the features usually considered to be characteristic of DH. And-reticulin antibody was found in eight patients, and in all of these IgA was present in the uninvolved skin. Low red cell folate levels were found in eleven patients (all of whom had an enteropathy and IgA in the uninvolved skin). Low serum folate levels were found in thirty-four patients, thirty-one of whom had IgA deposits in the uninvolved skin and an enteropathy; in the other three patients who did not have IgA deposits or an enteropathy, all were on dapsone and this may have accounted for the abnormal result. In forty-one of the forty-two patients the rash was dapsone responsive. The patient who showed no response to dapsone had no IgA in the uninvolved skin and no evidence of enteropathy. Follow-up showed that of the seven patients with no IgA in the skin, one had pemphigus, and in three the rash eventually cleared spontaneously and the patients no longer required treatment. There was no evidence of spontaneous remissions in the patients with IgA in the uninvolvcd skin. It would appear that the presence of IgA deposits in the uninvolved skin is part of the syndrome of DH and that the diagnosis should not be made unless these deposits are found.     

Comparison of immunoglobulin and complement deposition in multiple biopsies from the uninvolved skin in dermatitis herpetiformis

The distribution of immunoglobulins and C3 component of complement (C3) in the skin of twenty-four patients with dermatitis herpetiformis was studied. Skin biopsies were taken from three sites, the extensor surface of the elbow, the flexor surface of the forearm and from the thigh. Twenty-two (90%) patients showed variation in deposits of immunoglobulins and C3 at the three sites. IgA was present in all patients, but differed in quantities deposited at the three sites in nineteen (80%) patients. Similar variation between sites was observed with IgG, IgM and C3. There was variation within three biopsies, IgA being absent from some sections and present in others. Three patients had a continuous pattern of IgA deposition. One had both continuous and papillary deposits within a single section. There was no difference in the incidence or quantity of immunoglobulin and C3 between the elbow, forearm and thigh. There was observed to be a diminution in quantity of IgA and incidence of C3 in patients taking a gluten-free diet. Deposition of IgA, IgM, IgG and C3 is not uniform throughout the skin and conclusions drawn from the quantity of immunoglobulin and C3 in a single biopsy may not be reliable.     

Group A streptococcal antigen-specific T lymphocytes in guttate psoriatic lesions

A strong association exists between guttate psoriasis and group A, β-haemolytic streptococcal infections. To demonstrate the presence of streptococcal-specific T cells in psoriatic skin, T-cell lines (TLs) were established from biopsies of lesions from five patients with guttate psoriasis, and compared with TLs from five patients with eczema, five with lichen planus, two with pityriasis rosea and three with nickel contact dermatitis. TLs from purified protein derivative (PPD)-induced delayed hypersensitivity sites in three normal individuals were also studied. All five of the psoriatic TLs responded in a proliferation assay to heat-killed isolates of group A streptococci, compared with only one eczema, two lichen planus and one pityriasis rosea. The response of one nickel contact dermatitis and two PPD TLs to group A streptococci was markedly less than to nickel and PPD, respectively. One of the psoriatic TLs was cloned in the presence of type 5 streptococcal M protein. The nine clones obtained were all CD3⁺, CD4⁺, CD45RO⁺, TCR α,β⁺, γ,δ^?. However, they were all unreactive with antibodies to TCR V β 5, 6, 8 or 12. Eight of the nine clones reacted, to a varying extent, to one or two of three preparations of group A streptococci expressing different M proteins. The streptococcal response of four consistently reactive clones from this patient was HLA-DR-restricted and inhibited by anti-HLA-DR antibody in a dose-dependent manner. On stimulation these four clones secreted high levels of γ-interferon and detectable levels of IL-2, IL-10 and granulocyte/macrophage colony stimulating factor (GM-CSF) depending upon the nature of the stimulus, but no IL-4 or TNF-α production was detected. This study has demonstrated, for the first time, that T lymphocytes specific for group A streptococcal antigens can be consistently isolated from guttate psoriatic lesions. The role of streptococcal-specific T cells in the pathogenesis of psoriasis remains to be determined.     

Congenital Chylothorax and Persistent Pulmonary Hypertension of the Neonate

ABSTRACT. In this case of congenital chylothorax, an associated persistent pulmonary hypertension was a severe complication which has not hitherto been described. Recurrence of the chylothorax with the introduction of regular formula is also reported.     

Immunofluorescent studies in ocular cicatricial pemphigoid

Twenty nine patients with cicatrizing conjunctivitis were studied; 17 with a clinical diagnosis of cicatricial pemphigoid, five with a clinical diagnosis of pseudopemphigoid caused by long-term application of topical medication and seven who had a cicatrizing conjunctivitis from other causes. Biopsies from clinically uninvolved bulbar conjunctiva were taken for direct immunofluorescence and blood was taken for indirect immunofluorescence using normal human conjunctiva, oral mucosa and skin as substrates. On direct immunofluorescence, in vivo bound immunoglobulins were found along the basement membrane in 10 of the 17 patients with cicatricial pemphigoid, one of the five with pseudopemphigoid and two of the seven with a cicatrizing conjunctivitis associated with other diseases. Circulating anti-basement membrane zone antibodies were found only when conjunctiva was used as a substrate. These were present in seven of the patients with cicatricial pemphigoid, three of those with pseudopemphigoid and two of those with a cicatrizing conjunctivitis caused by other diseases. These results indicate that direct immunofluorescence is a useful, but not absolute diagnostic marker for ocular cicatricial pemphigoid. The results in the pseudopemphigoid group argue that this is an immunologically mediated disorder indistinguishable from spontaneous cicatricial pemphigoid and probably triggered by the drugs. The presence of circulating antibodies should allow for precise identification of the antigen involved in cicatricial pemphigoid using SDS electrophoresis and Western blot analysis.     

Synthesis,biological activity and conformational analysis of cyclic GRF analogs

A novel cyclic GRF analog, cyclo(Asp⁸-Lys¹²)-[Asp⁸,Ala¹⁵]-GRF(1-29)-NH₂, i.e. cyclo^8.12[Asp⁸,Ala¹⁵]-GRF(1-29)-NH₂, was synthesized by the solid phase procedure and found to retain significant biological activity. Solid phase cyclization of Asp⁸ to Lys¹² proceeded rapidly (～2h) using the BOP reagent. Substitution of Ala¹² with d -Ala² and/or NH₂-terminal replacement (desNH₂-Tyr¹ or N-MeTyr¹) in the cyclo^8.12[Asp⁸,Ala¹⁵]-GRF(1-29)-NH₂ system resulted in highly potent analogs that were also active in vivo. Conformational analysis (circular dichroism and molecular dynamics calculations based on NOE-derived distance constraints) demonstrated that cyclo^8.12[Asp⁸,Ala¹⁵]-GRF(1-29)-NH₂ contains a long α-helical segment even in aqueous solution. A series of cyclo^8.12 stereoisomers containing d -Asp⁸ and/or d -Lys¹² were prepared and also found to be highly potent and to retain significant α-helical conformation. The high biological activity of cyclo^8.12[N-MeTyr¹,d -Ala²,Asp⁸,Ala¹⁵]-GRF(1-29)-NH₂ may be explained on the basis of retention of a preferred bioactive conformation.     

Pemphigus controlled by sulphapyridine

A patient with an II-year history of a generalized blistering eruption is described. The eruption was completely controlled within I week of taking sulphapyridine and recurred within 4 days of with-drawal of this drug. On account of these observations a diagnosis of dermatitis herpetiformis was made. Histological, immunological (and small intestinal) studies now show that this patient had pemphigus.     

Disodium cromoglycate in dermatitis herpetiformis

Eleven patients with dermatitis herpetiformis, all requiring dapsone to control their rash and taking a normal diet, were given disodium cromoglycate (DSCG) 1.5–1.6 g daily. Eight out of the eleven patients continued to take DSCG for periods varying from 6–11 months, the other three patients chose to discontinue the DSCG before 6 months. Of the eight patients taking DSCG for at least 6 months, none was able to stop taking dapsone. In three of the eight, the dapsone requirements were unaltered, whilst in two it decreased and in three it increased. The mean daily dose of dapsone was 105 mg/day before DSCG and 141 mg/day after DSCG. In the eight patients who took DSCG for at least 6 months, intestinal biopsies were performed before and after this drug. The macroscopic appearance was unchanged in four, improved in two and worse in two. The mean interepithelial lymphocyte count was 346 before and 342 after DSG.