Biomedical subjects
Publications and source records attributed to D Zillikens.
We report the case of an 80-year-old woman who developed pemphigus foliaceus while taking penicillamine for rheumatoid arthritis. On the basis of this new case, we discuss fresh insights into the pathogenesis of drug-induced pemphigus. In addition, having reviewed the literature, we give a list of drugs that have been reported to induce this disease.
The interleukin-2 receptor (IL-2R) is mainly expressed on activated T cells. Depending on its rate of synthesis, a portion is released from the cell surface as soluble IL-2R (sIL-2R). Since the role of mononuclear cells in the pathology of bullous pemphigoid (BP) is not well understood, we determined the sIL-2R in both blister fluid and serum of 15 BP patients with generalized disease before initiating systemic treatment. In addition, we obtained both lesional and perilesional skin biopsies and examined the mononuclear infiltrate with a panel of monoclonal antibodies. In BP blisters, sIL-2R levels were significantly increased (2070 +/- 350 U/ml), (+/- SEM) compared with serum samples taken at the time of blister puncture (1340 +/- 290 U/ml). In six patients with blisters due to second-degree burns or friction and in five suction blister volunteers, sIL-2R levels were normal in both blisters and serum. In BP, elevated serum levels decreased to normal during therapy, correlating with disease activity. The immunohistology showed that 30% of mononuclear cells in the dermal infiltrate of lesional skin expressed the IL-2R, whereas only 15% were positive in perilesional skin. IL-2R-positive cells are the most likely source of the shed receptor in BP blisters. Our results indicate the presence of activated T cells in lesions and peripheral blood of BP and thus underline the importance of cell-mediated immune mechanisms in the pathology of this disease.
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In bullous pemphigoid, autoantibodies alone are not capable of blister formation. In addition, they need complement and various inflammatory cells. The role of mononuclear cells, however, is poorly understood. Therefore, we studied the inflammatory infiltrate in 21 patients with bullous pemphigoid and 11 controls (normal skin, n = 5; eczematous skin, n = 6) using a panel of monoclonal antibodies. In bullous pemphigoid, 60% of the mononuclear infiltrate consists of CD3+ T-lymphocytes, while 25% represents monocytes/macrophages (MOMA); B-lymphocytes are absent. In the area of the basement zone (BMZ), which was studied separately, MOMA predominate. In 30% of bullous pemphigoid biopsies we found a close, almost linear attachment of MOMA to the BMZ. Along the BMZ, lymphocytes belong to the CD3+, CD4+ T-helper subset. CD8+ T-cytotoxic-suppressor cells, however, are rarely encountered there, and other cytotoxic lymphocytes are not found at all. All lymphocytes along the BMZ are memory cells. In small, early bullous pemphigoid lesions, MOMA are frequently the only effector cells. Eosinophilic granulocytes are rare in these lesions. Our findings suggest that mononuclear cells, and particularly MOMA, may be more important than believed hitherto in the inflammatory process resulting in separation of the BMZ.
Incontinentia pigmenti is a rare genodermatosis typically involving three stages: vesiculae, verrucous lesions, and hyperpigmentation. We clinically and pathologically documented a case from shortly after birth until the age of 17 years. Although the first two stages took a regular course, the third stage of the disease was characterized by hypopigmented streaks on the legs in addition to axillary hyperpigmentation. Similar hypopigmented areas were found in the patient's mother. Because pathological investigations of hypopigmented areas have been extremely rare, we performed light and electron microscopic studies and compared these with our findings in hyperpigmented regions. Light microscopy showed the hypopigmented streaks with slight epidermal atrophy and a reduced number of melanocytes and skin appendages. However, the main finding was round eosinophilic bodies in the upper dermis. Electron microscopic examination of these bodies demonstrated amorphous material that resembled colloid, suggesting degeneration of basal keratinocytes. Confirming previous reports, in hyperpigmented areas we found a reduction of pigment in those parts of the basal layer overlying melanophages located in the upper dermis.
A 41-year-old woman presented with the typical clinical and pathohistological features of acute febrile neutrophilic dermatosis (AFND). The disease had been preceded by diarrhoea and vomiting for 2 weeks. Stool cultures proved positive for Salmonella typhimurium infection. Antibiotic therapy and tapering oral steroids led to a complete remission of skin lesions within 2 weeks. To our knowledge, this is the first report of Sweet's syndrome associated with salmonellosis.
Since 1989 there has been an increasing number of reports on the association of L-tryptophan (LT) and eosinophilia-myalgia syndrome (EMS). It has now become evident that the clinical picture of EMS can vary. We report two further cases reflecting the clinical spectrum of the disease. The first patient had been taking LT for 8 years before the onset of myalgia. Subsequently, this patient developed an illness clinically and histologically resembling eosinophilic fasciitis. The second patient had been taking LT for 8 months before the onset of symptoms, which included myalgia, severe oedema of the lower extremities and induration of the skin involving arms, lower legs and abdomen. Discontinuation of LT and administration of oral steroids resulted in little improvement of the skin changes in the first patient. However, in the second patient skin involvement improved rapidly, whereas the neurological disorders have become more prominent.
The treatment of granuloma annulare is still unsatisfactory. A number of topical and systemic therapies have been tried, some of which can improve the condition, but serious side effects are possible with those reported so far. We treated a patient with disseminated granuloma annulare by local application of a vitamin E emulsion and achieved a marked improvement within as little as 12 days.
An 84-year-old male with a 4-week history of vesiculobullous eruptions was diagnosed clinically and pathologically to suffer from pemphigus foliaceus. Amazingly, direct immunofluorescence demonstrated intercellular IgA deposits in the whole epidermis. The patient did not respond to a regimen of fluocortolone and azathioprine but rapidly improved under dapsone. The few reported dermatoses with intraepidermal IgA deposits do not form a homogeneous group. In the following, their spectrum will be outlined. It is important to distinguish these dermatoses from IgG pemphigus, since they require a different therapy.
We present the case of an 81-year-old women with progressive systemic scleroderma. In addition to the typical manifestations of diffuse (truncal) scleroderma, including involvement of the esophagus, lungs and muscles, there were two unusual findings: large, non-sclerosing areas on the trunk simulating the disabling type of circumscribed scleroderma and high titers of anticentromere antibodies, while there were no anti-Scl-70 antibodies. The disease responded to treatment with griseofulvin.
A sensitive radioimmunoassay for human parathyroid hormone (hPTH) to diagnose hypoparathyroid conditions is described. The antiserum was raised in goats against extracted hPTH. Synthetic human PTH fragment (53-84) is used as a standard and 125I-Tyr52hPTH (53-84) as a tracer. After a two-step incubation (24 h + 24 h) at 4 degrees C, the bound and free fractions are separated by a mixture of second antibody and polyethylene glycol solution. The detection limit for hPTH (53-84) is 2 pmol/L hPTH (53-84) (2 mol/tube). The PTH level in 36 healthy subjects was 5-12 pmol/L. Of 14 patients with hypoparathyroidism 11 patients had PTH concentrations below normal, two patients had levels on the lower limit of the normal range (5 pmol/L). The concentration of one patient with pseudohypoparathyroidism was markedly elevated. This assay is suitable for detecting low PTH levels and for studying changes of PTH concentration within the normal range.