Patchy dermal hypoplasia as a characteristic feature of Proteus syndrome.

BACKGROUND: The diagnostic criteria of Proteus syndrome include various lesions of localized overgrowth such as digital gigantism, hemihyperplasia with unilateral macrocephaly, epidermal nevus, and mesodermal hamartomas such as lipoma, lymphangioma, hemangioma, or fibroma. Hyperplasia of the plantar dermal tissue may result in a characteristic cerebriform appearance. However, hypoplastic lesions involving various tissues such as subcutaneous fat or muscles also may be observed in this syndrome. This paradoxical phenomenon has so far been underestimated, and the presence of circumscribed lesions of dermal hypoplasia has been entirely ignored. OBSERVATIONS: We report 4 cases of Proteus syndrome associated with large patches of dermal hypoplasia, resulting in a more prominent appearance of venous vasculature. CONCLUSIONS: Patchy dermal hypoplasia appears to be a characteristic feature within the spectrum of Proteus syndrome. The anomaly should not be confused with partial lipohypoplasia that may likewise be associated with this multisystem birth defect. From a review of the literature, we conclude that patchy dermal hypoplasia may have occurred in several previous cases. In the future, recognition of this cutaneous anomaly may help to establish the diagnosis in otherwise doubtful cases. To explain the coexistence of lesions of dermal hyperplasia and hypoplasia, we propose the genetic concept of "twin spotting." At the gene locus of Proteus syndrome the embryo would carry 1 allele giving rise to dermal overgrowth, whereas the corresponding allele would be responsible for a diminished proliferation of cutaneous fibroblasts. Somatic recombination may result in 2 different populations of cells homozygous for either allele.

Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): response to methotrexate and mercaptopurine.

We report a 3-year-old girl presenting with bilateral cervical lymph node enlargement persisting for > 3 months. Leukocytosis, elevated erythrocyte sedimentation rate, a marked hypergammaglobulinemia, and a moderate hepatosplenomegaly were also found. The diagnosis of sinushistiocytosis with massive lymphadenopathy (SHML), also known as Rosai-Dorfman disease, was established histologically by the demonstration of characteristic sinushistiocytosis with lymphocytophagocytosis. Treatment was started with high dose steroids, and a decline of lymph node size and a normalization of laboratory parameters occurred. However, when steroids were tapered, lymph node size rapidly reincreased. Chemotherapeutic treatment was started using etoposide, which was completely ineffective. Therefore, treatment was changed to a combinatory low dose methotrexate therapy and 6-mercaptopurine for 4 months. Whereas a prompt and complete remission was reached, single 6-mercaptopurine therapy was maintained and treatment has been discontinued after a total of 2 years. The child has remained healthy for 7 years. This case would recommend the use of methotrexate and 6-mercaptopurine for treatment of complicated SHML.

[Acute pancreatitis as an initial manifestation of hypercalcemia in primary hyperparathyroidism in childhood]. / Akute Pankreatitis als Erstmanifestation einer Hypercalcämie bei primärem Hyperparathyreoidismus im Kindesalter.

A 12-year-old girl was admitted to our hospital with signs of an acute abdomen with paralytic ileus. The previous and family history were without abnormalities. Abdominal pain and vomiting had started two days earlier. On palpation the swollen abdomen was painful and there was an increased tension in the left upper part. The clinical diagnosis of acute pancreatitis was confirmed by an increased serum level of lipase (4480 U/l). Clinical chemical investigations further revealed a permanent hypercalcemia in the range of 6.4 to 8.3 mval/l. This, together with concomitantly reduced levels of serum phosphate and a threefold increased level of parathyroid hormone (343 pg/ml, upper limit of reference = 100 pg/ml) were consistent with a hyperparathyroidism. In fact, sonography of the cervical organs revealed a solitary adenoma of the parathyroid glands. After surgery serum levels of calcium returned to normal. Hypercalcemia as a consequence of primary hyperparathyroidism has to be included in the differential diagnosis of acute pancreatitis in childhood.

[Neonatal septicemia and bacterial neonatal infection. Manifestation and course in early antibiotic therapy]. / Neugeborenensepsis und bakterielle Neugeboreneninfektion. Manifestation und Verlauf unter frühzeitiger Antibiotika-Therapie.

The authors studied in the Paediatric Department of the Leverkusen Municipal Hospital retrospectively the influence of an early dose of antibiotics (broad-spectrum penicillin combined with an aminoglycoside) in respect of the manifestation of bacterial newborn infections in infants with an increased risk of infection, during a period of 3 years (1981-1983). Among the infants born in the Gynaecological Department of the Leverkusen Municipal Hospital (exact data were available on the number of births and referrals) the incidence of bacterial newborn infections was 3.3% referred to the total number of deliveries (n = 3598); 0.7% of these newborn has sepsis. In the total group of children treated for newborn infection, the infection mortality was 5.5%; the mortality of the manifest newborn sepsis was 16.2%, i.e. lower than reported in literature. Early administration of antibiotics proved particularly effective in preventing purulent bacterial meningitis of newborn; this disease did not occur with any of the infants observed during the study period. Diagnosis of newborn infection included discolouration of the skin, respiratory disturbances, fever, shift to the left in the differential blood picture, and anaemia; these signs proved particularly suitable for arriving at a correct diagnosis. Identification of the pathogens was most frequently successful in gastric juice culture and anal smear. The latency period of more than 24 hours between rupture of the amnion and delivery does not represent an increased risk of infection for the newborn, as our results confirm, and this is, therefore, not an indication for initiating prophylaxis with antibiotics if there are no other abnormal findings.

[Lung functions in children with marked alpha 1-antitrypsin deficiency (Pi-Z type) (author's transl)]. / Die Lungenfunktion bei Kindern mit ausgeprägtem alpha 1-Antitrypsin-Mangel (Pi-Typ Z).

Various lung volumes and flows were measured in five children (aged 9-11 years), a male adolescent and one adult, all carriers of the homozygotic form of alpha 1-antitrypsin deficiency (Pi-Z type). In five patients lung function tests demonstrated overdistention, in three decreased CO diffusion capacity, as an expression of pulmonary emphysema at an early stage. Airway obstruction was not demonstrable in any of the patients (normal values for FEV 1, Tiffeneau test, peak flow and V25, V50 and V75). There was a correlation between the level of alpha 2-macroglobulin and the CO diffusion capacity, as well as between alpha 1-antitrypsin level and residual volumes. In one child there was evidence of minor liver involvement; in the other six patients, all liver-dependent serum enzymes were within normal limits. The findings suggest that the lung changes typical of adult homozygotic carriers of alpha 1-antitrypsin deficiency have their beginning in childhood.

The prognostic significance of specific IgG antibodies in insect sting allergy.

Specific IgG antibodies against bee venom and bee venom components were studied in the serum of 40 bee-sting patients, 60 bee keepers, and 31 control subjects. The highest titres were observed in successfully hypothesized patients and in bee keepers. Subclass-typing in bee-sting allergic patients showed the highest antibody levels in subclass IgG2, followed by IgG3, IgG 4 and IgG1. During hyposensitization, a rise in specific IgG antibodies in all subclasses and against bee venom and all its components was found. The allergic reaction to bee stings disappeared with the rise of specific IgG antibodies, as demonstrated by a bee-sting challenge. After 6 months of hyposensitization therapy, the specific IgG antibodies remained above, and the specific IgE antibodies fell below, the pretreatment levels.

Immunological studies on bee-keepers: specific IgG and subclass typing IgG against bee venom and bee venom components.

Specific IgE antibodies against bee venom and its components were studied in 23 bee-keepers. The highest IgG serum levels were observed for whole bee venom followed by phospholipase A. The serum levels of specific IgG antibodies against melittin and MCD-peptide were lower, the lowest serum levels being observed for apamin. After a 5 month absence from bee-keeping a fall in the serum levels of IgG antibodies was observed in all the bee-keepers studied. The investigation of the IgG subclass antibodies 1-4 against bee venom and phospholipase A demonstrated the highest serum levels for IgG 4 and IgG 2, the lowest levels were observed for IgG 1. The lowest IgG serum levels were associated with the least effective protection to bee stings. These findings support the concept that specific IgG antibodies prevent the development of allergic symptoms after bee sting.

[Recovery of hypothalamic-pituitary-adrenocortical axis after high-dose dexamethasone treatment (author's transl)]. / Untersuchungen zur Erholung der Hypothalamus-Hypophysen-Nebennierenrindenachse nach hochdosierter Dexamethason- Therapie.

High doses of dexamethasone (Fortecortin) for the prophylaxis of cerebral oedema were administered to 19 children aged 3 to 14 years because of head injury of varying degrees of severity. In order to assess possible suppression of the hypothalamic-pituitary-adrenocortical activity an insulin tolerance test and an intravenous tetracosactid (Synacthen) test was performed 1 to 26 weeks after the last dexamethasone dose. There was no evidence from the insulin tolerance test of inadequate cortisol excretion. After intravenous Synacthen injection satisfactory serum cortisol increase was found. However, from this test there was evidence of a lesser increase of serum cortisol depending on the time elapsed since cessation of dexamethasone. Investigation of circadian cortisol values showed 7 cases with subnormal serum cortisol at 18 o'clock independent of the time elapsed. The hypothalamic-pituitary-adrenocortical axis was functioning again during induced stress 7 days after withdrawal of dexamethasone. Subsequent stress situations do not require treatment with corticoids.

[The albumin-IgG ratio in the CSF in inflammatory diseases of the CNS (author's transl)]. / Das Albumin-IgG-Verhältnis im Liquor bei entzündlichen Erkrankungen des Zentralnervensystems.

Levels of albumin and IgG in the cerebrospinal fluid were determined in 69 children with infectious diseases of the central of the central nervous system in the years 1975 to 1978. The cerebrospinal fluid in 63 children without infectious diseases of the central nervous system, serving as a control, showed a close correlation between albumin and IgG levels. In the acute stages of serous and purulent meningitis (meningococci, streptococci, and hemophilus influenzae) however, IgG levels in the cerebrospinal fluid were overproportionately high. Very high yet correlating levels of IgG and albumin were found in purulent meningitis due to Escherichia coli. The determination of cerebrospinal fluid levels of albumin and IgG renders information about the function of the blood cerebrospinal fluid barrier, as well as about any significant production of IgG at these sites. In case of repeated determinations information about the course of inflammation and the efficacy of antibiotic therapy can be obtained. This technique is simple and inexpensive. For one determination only 50 microliter of cerebrospinal fluid is required.

[Suggestion for treatment of primarily inoperable omphalocele (author's transl)]. / Vorschlag zur konservativen Behandlung primär nicht operabler Omphalozelen.

Bending primarily inoperable omphalocele can be avoided by simply using Stülpa tube-dressing together with a spongering. Epithelising under the employment of tannin or Betaisodona becomes much easier if this method is used.

[Hyposensitisation treatment with pure bee venom (author's transl)]. / Die Hyposensibilisierungsbehandlung mit reinem Bienengift.

Hyposensitisation with pure bee venom was undertaken in eleven persons with proven allergy to bee stings. Rapid hyposensitisation led to side effects in seven of them during dosage increase. Serial determination of total IgA, IgG, IgM and alpha1-antitrypsin revealed no changes, while allergen-specific IgG and IgE and total IgE increased maximally after 30 days. All persons were exposed to one bee sting during the treatment: all tolerated it well without the allergic reactions which had previously been noted.

[Serum IgE in skin diseases of children (author's transl)]. / Serum-IgE bei Hauterkrankungen im Kindesalter.

Using the paper-radioimmunosorbens test (PRIST) normal values were obtained from 200 non-allergic children. The IgE level was aged-dependent, in part with significant differences between various age groups. These normal values were compared with those in children with seborrhoeic dermitis, constitutional neurodermatitis, parasitoses, urticaria, Quincke oedema, Schönlein-Henoch purpura, pityriasis rosea, multiform exudative erythema, erythema nodosum and infantile papular acrodermatitis. Half-life of IgE in neonates was 16.2 hours.

[Liver disease in homozygous alpha1-antitrypsin deficiency (author's transl)]. / Hepatopathie bei homozygotem alpha1-Antitrypsin-Mangel.

Among twelve patients with homozygous alpha1-antitrypsin deficiency (Pi-type Z), five cases of infantile liver disease were diagnosed. The course of the disease was extremely variable; only one patient died of liver cirrhosis at the age of fourteen. In four cases the clinical, biochemical and histological (2 cases) findings became normal over a follow-up period of one to fifteen years. The results of these observations demonstrate that in alpha1-antitrypsin deficiency even when associated with proven liver disease the prognosis need not be unfavorable.

[Prolonged jaundice by heterozygous alpha-1-antitrypsin-deficience? (author's transl)]. / Ikterus prolongatus durch heterozygoten Mangel an Alpha-1-Antitrypsin?

Of 28 newborns with prolonged jaundice and lowered or subnormal values of alpha-1-antitrypsin in the serum six patients were found to have a Pi-type MZ, three a Pi-type MS and one patient a Pi-type MP. One of the newborns had Pi-type SZ (double heterozygous), one infant was a homozygous carrier of the Pi-type S. It seems to the possible that one of the reasons for the not yet explained cases of prolonged jaundice of the newborns period can be found in the high frequency of homozygous or heterozygous genotype carriers of Pi-system.

[Allergy to insect stings (author's transl)]. / Die allergische Reaktion nach Insektenstich.

Generalised reactions after an insect bite call for an exact diagnosis: nonspecific general reactions must be distinguished from true allergic reactions. 12 children with allergic reactions to bee and/or wasp stings were investigated. The results of the skin tests and the allergen-specific IgE determinations were compared and found to vary distinctly in some cases. In addition to immediate therapy (emergency pharmacy), specific hyposensitization over several years is indicated. Observation of the course of IgE antibodies is presented.