[Diagnostic image (107). A man with weight loss and skin nodes]. / Diagnose in beeld (107). Een man met gewichtsverlies en huidknobbeltjes. Huidmetastasen van een longcarcinoom.

A 63-year-old man who presented with loss of weight and skin nodes on head and hands was diagnosed with pulmonary carcinoma.

[The pathophysiology and treatment of cholestatic pruritus]. / De pathofysiologie en behandeling van cholestatische jeuk.

Pruritus is a frequent, distressing and sometimes disabling symptom of liver and biliary tract disorders. Results of treatment are sometimes disappointing and the pathophysiology is still largely unknown. It was recently discovered that endogenous opioids contribute to the perception of itching and that opiate receptor antagonists can reduce the overstimulation of these receptors and thereby attenuate the itching. A stepwise treatment strategy focusing successively on ion exchange resins, rifampicin and opiate receptor antagonists leads to effective alleviation of itching in most patients.

Hepatitis in a patient with SLE: is it autoimmune hepatitis?

In a patient with systemic lupus erythematosus (SLE), we considered the diagnosis of autoimmune hepatitis (AIH) in view of raised serum aminotransferases, hypergammaglobulinaemia, antinuclear antibodies (titre 1:10,240), seronegativity of markers for viral hepatitis and absence of recent hepatotoxic drug usage. The diagnosis of AIH was supported by using the scoring system, recently developed by the International Autoimmune Hepatitis Group and the excellent response to treatment with prednisone. Liver histology, however, showed no characteristic features of AIH. The relevance of liver histology and scoring for AIH in SLE with hepatic involvement is discussed.

The importance of different components of normal human serum and lysozyme in the rapid immobilisation of purified Treponema pallidum, Nichols strain.

OBJECTIVES: To study the role of different components in normal human serum and the role of lysozyme in rapid immobilisation of Percoll purified T pallidum (Nichols). MATERIALS AND METHODS: The immobilisation of Percoll purified T pallidum was studied after pre-incubations with different serum fractions (Fr) of normal human serum (Fr 1, containing IgM; Fr 2, containing IgG and a low level of haemolytic complement, and Fr 1 (abs), depleted of IgG). A guinea-pig serum pool was used as a complement source in the immobilisation experiments. The influence was studied of removal of lysozyme from guinea-pig serum on the immobilisation reactions. Further experiments were performed, using a fluorescence technique, to detect C3b depositions on fixed treponemes and treponemes in suspension. RESULTS: Rapid immobilisation of Percoll-purified treponemes by the NHS serum fractions occurred only after preincubation with Fr 1 and Fr 2 simultaneously. This was largely dependent on the presence of a small amount of haemolytic C in Fr 2. Removal of lysozyme reduced this rapid rate of immobilisation. In fluorescence experiments it was demonstrated that C3b deposition on fixed (that is damaged) treponemes occurred upon their incubation with Fr 2 or the combination of Fr 1 and 2. However, on treponemes in suspension C3b deposition occurred only after incubation with the combination of Fr 1 and 2. CONCLUSION: The rapid immobilisation of Percoll purified treponemes by serum fractions from normal human serum requires antibodies of the IgM and IgG class, together with complement and lysozyme. Omission of one of these reactants slows immobilisation. Our experiments suggest that the reactants act in sequence: the loss of integrity of the outer membrane by an attack by IgM and C offers the opportunity for lysozyme to hydrolyse the peptidoglycan layer surrounding the cytoplasmic membrane of the treponemes, which then is accessible for attack by antibodies and C.

The localisation of treponemes and characterisation of the inflammatory infiltrate in skin biopsies from patients with primary or secondary syphilis, or early infectious yaws.

OBJECTIVE: To study the localisation of treponemes and to analyse the inflammatory infiltrate in biopsy specimens from patients with primary or secondary syphilis, or early infectious yaws. MATERIALS AND METHODS: Skin biopsies originating from human lesions of primary (29x) or secondary (15x) syphilis (Rotterdam), or early yaws (18x) (West Sumatra) were studied. Different histochemical and immunohistochemical detection methods were used in this study. RESULTS AND CONCLUSION: The histochemical silver staining method according to Steiner revealed the presence of T. pallidum in all cases of primary syphilis studied. In 10 out of 14 cases of secondary syphilis, treponemes were demonstrated. With an immunofluorescence staining technique (IF) using anti-T. pallidum antiserum raised in rabbits (a-Tp), T. pallidum was demonstrated in 28 out of 29 cases of primary syphilis, and in 14 out of 14 studied cases of secondary syphilis. The silver staining method and IF showed identical localisations of T. pallidum (mainly in the dermal-epidermal junction zone or throughout the dermis). Using a-Tp antiserum in the indirect immunofluorescence technique, T. pertenue could be demonstrated in the dermis more often than with Steiner silver staining. However, epidermotropism of T. pertenue in yaws specimens was remarkable, compared with more mesodermotropism of T. pallidum; numbers of T. pertenue in the dermis were limited in all specimens. The dermal inflammatory infiltrate in primary and secondary syphilis was composed mainly of lymphocytes and plasma cells. In most cases more T (CD3 positive) cells than B (CD22 positive) cells were present. Regarding T cell subpopulations, in primary syphilis, T helper/inducer (CD4 positive) cells predominated in 86% of cases. In secondary syphilitic lesions, numbers of T helper/inducer cells were less frequent than or equal to T-suppressor/cytotoxic (CD8 positive) cells in 60% of cases. Remarkably, in yaws specimens the inflammatory infiltrate consisted mainly of IgG, but also IgA and IgM producing plasma cells. T or B lymphocytes were scarce, which is in sharp contrast with findings in syphilitic lesions.

The influence of different sera on the in vitro immobilisation of Percoll purified Treponema pallidum, Nichols strain.

OBJECTIVES: Investigation of sera, especially rabbit serum, in preventing in vitro immobilisation of Percoll purified T. pallidum. MATERIALS AND METHODS: The immobilisation of Percoll purified T. pallidum (Nichols) was studied after pre-incubations with basal reduced medium (BRM), heat-inactivated serum of seven different species of animals, heat-inactivated normal human serum (NHS) and rabbit sera containing a different level of antitreponemal antibodies. Also increasing percentages of heat-inactivated normal rabbit serum (NRS) were studied. RESULTS: The rapid immobilisation of purified treponemes by NHS is delayed by pre-incubation with NRS in a dose-dependent manner. The treponemes from 5-day infections were immobilised significantly more slowly than treponemes from 7- and 8-day infections. Compared with NRS, pre-incubations with a high-titred, low-titred and "autologous" serum resulted in significantly more rapid immobilisation of the treponemes. With most other animal sera resistance to immobilisation was slight compared with that produced by NRS. Immunofluorescent studies revealed that the treponemes were covered with a layer of the human third complement factor (C3b), within an hour of incubation. With two sequential pre-incubations, a delay of the immobilisation was only noted in those test mixtures in which NRS had been present in both preincubations. CONCLUSION: Rabbit serum delays the rapid in vitro immobilisation of Percoll purified treponemes by normal human serum. There was no evidence that this was caused by preventing access of antibodies (in vivo as well as in vitro) to, or preventing the activation of complement on, the treponemal surface. The evidence points to a mechanism in the fluid phase, suggesting participation of a third factor in the immobilisation process, for instance an enzyme, which can be partially inhibited by rabbit serum component(s).

A small yaws survey on the island of Sumatra, Indonesia.

Yaws (framboesia tropica), caused by Treponema pallidum subspecies pertenue, is a chronic infectious disease, found in tropical rural regions. As a result of mass treatment campaigns conducted in the 1950s and 1960s the prevalence of yaws and the other endemic treponematoses (pinta and endemic syphilis) has decreased greatly. However, in several tropical regions in the world resurgence of yaws was reported in the 1980s. In this article we present the results of a small survey on yaws in six health centres in the Pariaman region in West Sumatra, Indonesia. A general conclusion from this small survey is that yaws is far from being eradicated and that in this region the disease is on the increase again. Some major findings of T. pertenue research are presented here.

Case report 724. Yaws.

A 15-year-old girl presented with the typical clinical, serological, and pathological lesions of yaws. The patient was a native of Sumatra. The important diagnostic criteria and the relationship to venereal syphilis were discussed.

Ultrastructural aspects of infection with Treponema pallidum subspecies pertenue (Pariaman strain).

OBJECTIVE: To study ultrastructural aspects of infection with Treponema pertenue (Pariaman strain), originating from West Sumatra, Indonesia. MATERIALS AND METHODS: Biopsy material originating from skin lesions in ten young children suffering from early infectious yaws in Indonesia, and rabbit testicular tissue inoculated with T pertenue. Human skin as well as rabbit testicular tissue was examined by means of conventional electron microscopy. RESULTS: In human skin, treponemes were found in interepidermal spaces in 5 out of 10 specimens. In two of five positive specimens, treponemes were also seen in the dermis. In one out of five specimens from rabbit testicular tissue a profusion of treponemes was found lying in the interstitial myxomatous tissue. Microorganisms showed no adhesion to fibroblasts. CONCLUSION: This ultrastructural study of T pertenue demonstrated the scarcity and focal distribution of treponemes in tissue and did not reveal any morphological differences from the Gauthier strain of T pertenue. No differences from the ultrastructure of T pallidum were observed either.

Primary and secondary syphilis: a histopathological study.

We present a study of biopsies taken from skin lesions of 44 patients presenting with primary or secondary syphilis. In most primary lesions erosion or, more often, ulceration was present, with a dense inflammatory infiltrate. In secondary syphilis a wide variety of histological changes was present. Blood vessels were frequently involved, with marked endothelial swelling and often proliferation. Treponemes were demonstrated with the Steiner staining method in all investigated cases of primary syphilis and in 71% of secondary syphilis cases. Treponemes were present throughout the dermis, particularly perivascularly, and in the dermal-epidermal junction zone. In two specimens of secondary syphilis treponemes were located predominantly in the epidermis, but there were always some microorganisms demonstrable in the dermis. The inflammatory infiltrate was often located in a perivascular coat-sleeve-like arrangement. In this study plasma cells and lymphocytes were present in all specimens of primary and secondary syphilis. Syphilitic lesions differed from yaws lesions mostly in the location of treponemes and the affection of blood vessels. In this histopathological study of early syphilis, treponemes did not show the epidermiotropic character of yaws, and blood vessel changes were more pronounced than in yaws. Unfortunately, due to the protean histopathological manifestations described in venereal syphilis and in yaws, these two treponemal diseases cannot always be differentiated on histological grounds alone.