Late neonatal lupus erythematosus onset in a child born of a mother with primary Sjögren's syndrome.

BACKGROUND: The neonatal lupus syndrome can be present as congenital heart block (CHB) or as neonatal lupus erythematosus (NLE), both seldom passively acquired autoimmune diseases. CHB starts around week 20 of pregnancy and is a lifelong event, whereas NLE is self limiting and usually starts at the 6th week of the child's age-the maximum recorded up to week 20. CASE REPORT: An asymptomatic mother with primary Sjogren's syndrome and anti-SSA/Ro52, anti-SSA/Ro60, and anti-SSB/La autoantibodies is described who, at gestational week 23 during her first pregnancy, was diagnosed as having a male fetus with CHB due to third degree atrioventricular block. The boy from the second pregnancy developed skin eruptions which clinically and by biopsy were compatible with NLE at week 20+1 post partum. CONCLUSIONS: Our case of NLE, starting at week 20+1 of age, seems to be the latest reported clinical case of NLE. Development of CHB and NLE in two consecutive boy pregnancies is unusual.

Systemically induced photoallergy to quinine in the mouse can be elicited topically--and vice versa.

Groups of female albino mice were photosensitized and photochallenged to quinine using protocols for either systemic or epicutaneous administration. Compared with control groups, statistically significant inflammatory reactions, measured as wet weight increase in ear tissue, could be obtained both with systemic and epicutaneous administration. Topically induced photoallergy to quinine could be elicited not only by topical, but also by intraperitoneal administration of the drug, and vice versa. The strongest response at challenge was obtained when the induction was performed topically and the challenge by the systemic route. These data suggest that epicutaneous and systemic photoallergy to quinine have mechanisms in common, and that the route of introduction of the sensitizer into the skin is not the crucial factor. This experimental model may be useful in the elucidation of the mechanisms of systemic photoallergy.

Quinine and quinidine cross-react after systemic photosensitization in the mouse.

Using a protocol for induction of photoallergy in the mouse after systemic administration, quinine was shown to be just as potent a photosensitizer as its d-isomer, quinidine. The dose-response curves for the two isomers followed a similar course both for induction and elicitation. Cross-reaction experiments, where induction and challenge were performed with different isomers, indicated that quinine and quinidine cross-react. Traces of the isomer as a contaminant in the test compound are not likely to account for this cross-reactivity. For practical purposes, photosensitization to one of these two quinoline methanol isomers seems to exclude the future use of the other.

Dynamics of systemic quinidine photoallergy in the mouse.

Photoallergy to systemically administered quinidine was induced in the mouse, and the minimal time for sensitization as well as the duration of the allergy were studied. When groups of female albino mice, pretreated with cyclophosphamide, were exposed to quinidine 100 mg/kg i.p. followed by 0.1 J/cm2 UVB and 5.0 J/cm2 UVA, a positive challenge reaction, measured as ear edema, could be registered as early as the third day after induction and peaked on days 5-12. When animals photosensitized as above were photochallenged after 7 days, and again after 2 and 8 months, strong reactions were obtained on all 3 occasions, suggesting a duration of systemically induced photoallery to quinidine of more than 8 months. In the absence of quinidine, no photosensitivity could be demonstrated with UVA only. Phototoxicity controls were negative. These results suggest that photoallergy induced by systemic administration behaves similarly to contact and photocontact allergy.

Photoallergy to systemic quinidine in the mouse: dose-response studies.

Photoallergic dermatitis was induced in the mouse following the systemic administration of quinidine in combination with UVB and UVA. The reaction was recorded as ear wet weight, ear thickness and tail wet weight. Statistical calculations showed ear wet weight to be the most sensitive evaluation technique. By varying the quinidine dose administered in induction (2.5-100 mg/kg) and challenge (10-100 mg/kg), dose-response conditions were established. It was shown that the induction dose necessary to obtain a statistically significant reaction was considerably lower than the minimal challenge dose (25 mg/kg). This method is well suited for studies of the dynamics of the induction and elicitation phases of systemically induced photoallergy.

Phototoxic properties of quinine and quinidine: two quinoline methanol isomers.

Clinical photoreactions have been reported for quinine and quinidine after systemic and topical administration. We have investigated the phototoxic properties of these two quinoline methanol isomers in vitro using the Candida albicans inhibition test and photohemolysis, and in vivo with the mouse tail phototoxicity test. Both isomers were phototoxic in the hemolysis model, quinine being the more potent compound. In the Candida test only quinidine was phototoxically active. In the mouse tail model, measuring edema, the phototoxic activity of quinidine was comparatively low, causing a 7.3% wet weight increase of tail tissue at a dose of 150 mg/kg intraperitoneally of drug and 54 J/cm2 of UVA. In spite of its structural similarity to quinidine, quinine was not phototoxic in the mouse. These studies support the assumption, based on clinical data, that quinine photoreactions probably have a non-phototoxic mechanism. For quinidine, however, light-induced reactions based on phototoxicity can not be ruled out, since low-grade phototoxic properties were demonstrated in vivo.

Photoallergy to systemic quinidine in the mouse.

Using the mouse, photoallergy to the antiarrhythmic agent quinidine could be induced following systemic administration. After pretreatment with cyclophosphamide 150 mg/kg, groups of 5-10 mice were injected i.p. with quinidine chloride 100 mg/kg on 2 consecutive days, followed by exposure of shaved abdominal skin to UVB 0.1 J/cm2 and UVA 5.0 J/cm2. Five days later challenge was performed on the left ear and on the tail, using the same dose of quinidine and UVA 5.0 J/cm2. The reaction was elevated 24 h later by measuring the increase in ear thickness as well as the wet weight increase of ear and tail. Significant 24 h reactions could be measured using all three evaluation systems. Control animals treated according to the protocol, but not UV-exposed during induction, were negative, thus excluding a phototoxic reaction. The histology of the left ear at challenge showed a round cell infiltrate preferentially of the exposed outer face of the ear consistent with an immunologic reaction. The time course of the reaction showed a maximum at 24 h. Photosensitization to quinidine could be achieved with UVA alone during the induction phase. Quinidine photoallergy can be induced in the mouse after systemic administration, and the reaction measured both at ear and tail. These findings support the assumption that clinical photoreactions to quinidine may have an immunological basis.

Urinary excretion of 6-hydroxy-5-methoxyindole-2-carboxylic acid and 5-S-cysteinyldopa during PUVA treatment.

The urinary excretion of the eumelanin metabolite 6-hydroxy-5-methoxyindole-2-carboxylic acid and the pheomelanin metabolite 5-S-cysteinyldopa was followed during PUVA treatment for 6 weeks. They showed similar excretion patterns, with the highest values within 1-2 wk.

Urinary excretion of melanocytic metabolites in fertile women.

Pregnant women and women taking oral contraceptives show urinary excretion values of 5-S-cysteinyldopa and of 6-hydroxy-5-methoxyindole-2-carboxylic acid in the same range as nonpregnant women not taking oral contraceptives. The excretion of these melanoma markers can therefore be used in in the biochemical diagnosis of metastatic melanoma in pregnancy and in women taking oral contraceptives.

Oxidation of dopa in human albinism.

The urine of an albino woman contained small quantities of 5-S-cysteinyldopa; 6-hydroxy-5-methoxyindole-2-carboxylic acid, a melanin precursor metabolite, was lacking. The 5-S-cysteinyldopa excretion observed may reflect non-specific oxidation of dopa. Two other albino patients showed normal values for the excretion of 5-S-cysteinyldopa and of 6-hydroxy-5-methoxyindole-2-carboxylic acid.

Melanocyte metabolites in the urine of people of different skin colour.

The urinary excretion of 2 melanocyte metabolites was studied in normal people of different skin type. The sulphur-free indole derivative 6-hydroxy-5-methoxyindole-2-carboxylic acid was excreted in larger quantities by people with genetically dark skin, whereas the excretion of 5-S-cysteinyldopa was not related to pigment type. No correlation between 5-S-cysteinyldopa and 6-hydroxy-5-methoxyindole-2-carboxylic acid excretion emerged.