Erythema induratum Erythema nodosum Granuloma annulare

What is the diagnosis?
Erythema induratum
Erythema nodosum
Granuloma annulare
Necrobiosis lipoidica
Pretibial myxedema
Necrobiosis lipoidica is a chronic granulomatous dermatitis of unknown cause that is most often
associated with diabetes mellitus. However, in about 25% of patients with this condition, lesions
develop before the onset of diabetes. The lesions appear as yellow-brown, telangiectatic plaques
with central atrophy and raised violaceous borders. They occur most frequently on the shins or the
dorsa of the feet. Ulcers, which exist in about 30% of lesions, are often induced by trauma.
Noduläre Vaskulitis
Erythema induratum
Erythema nodosum
Pretibial myxedema
Granuloma annulare
granulomatösen Hauterkrankungen
Necrobiosis lipoidica
Darmkrebs ist in Deutschland bei Männern und
Frauen die zweithäufigste Krebserkrankung, an
der mehr als sechs Prozent aller Deutschen im
Laufe ihres Lebens erkranken. Kolorektale
Karzinome verursachen zunächst sehr selten
Symptome, sie entstehen fast immer aus
anfangs gutartigen Darmpolypen. Die
Heilungschancen durch Operation und
Chemotherapie mit 5-Jahres-Überlebensrate
von 40 bis 60 % im Mittel hängen entscheidend
vom Krankheitsstadium ab, in dem der
Darmkrebs entdeckt wird. Seit 2002
übernehmen die Krankenkassen in Deutschland
für alle Versicherten ab dem 55. Lebensjahr im
Abstand von jeweils mindestens zehn Jahren die
Kosten einer Darmspiegelung („VorsorgeKoloskopie“), um durch Entfernung etwaiger
Polypen dem kolorektalen Karzinom
vorzubeugen.
Die einzelnen Darmabschnitte sind ungleich häufig betroffen, 60 % der Tumoren befinden sich
im linken Anteil des Dickdarms (jenseits der linken Colonflexur) und 25 % im Caecum und dem
übrigen rechten Dickdarm. Von den linksseitigen bösartigen Dickdarmtumoren sind etwa 55 %
in der Sigmaschlinge (Colon sigmoideum) und im Rectum lokalisiert. Die wichtigsten
Risikofaktoren sind hohes Alter und das Vorkommen von Darmpolypen. Diese entarten häufig.
Flexible sigmoidoscopy enables
the physician to look at the inside
of the large intestine from the
rectum through the last part of the
colon, called the sigmoid or
descending colon. Physicians may
use the procedure to find the
cause of diarrhea, abdominal pain,
or constipation. They also use it to
look for early signs of cancer in
the descending colon and rectum.
With flexible sigmoidoscopy, the
physician can see bleeding,
inflammation, abnormal growths,
and ulcers in the descending colon
and rectum. Flexible
sigmoidoscopy is not sufficient to
detect polyps or cancer in the
ascending or transverse colon
(two-thirds of the colon).
Colorectal-Cancer Incidence and Mortality with Screening Flexible
Sigmoidoscopy
The benefits of endoscopic testing for colorectal-cancer screening are uncertain. We evaluated
the effect of screening with flexible sigmoidoscopy on colorectal-cancer incidence and mortality.
From 1993 through 2001, we randomly assigned 154,900 men and women 55 to 74 years of age
either to screening with flexible sigmoidoscopy, with a repeat screening at 3 or 5 years, or to
usual care. Cases of colorectal cancer and deaths from the disease were ascertained. Colorectal
cancer is the second leading cause of cancer-related deaths in the United States.
Colorectal-cancer mortality and incidence are reduced with screening by means of fecal occultblood testing. Endoscopic screening with flexible sigmoidoscopy or colonoscopy is more
sensitive than fecal testing for the detection of adenomatous polyps, the precursor lesions of
colorectal cancer. Three European randomized trials of flexible sigmoidoscopy have been
performed. In the United Kingdom, one-time screening with flexible sigmoidoscopy significantly
reduced the incidence of colorectal cancer (by 23%) and associated mortality (by 31%). In Italy,
an 18% reduction in incidence and a nonsignificant 22% reduction in mortality were observed,
whereas in Norway, no benefit was observed after 7 years of follow-up
There were 3 bowel perforations, 2 by the same operator, in 107,236 flexible sigmoidoscopic examinations (2.8
per 100,000). Among participants with a positive flexible sigmoidoscopic examination and no cancer detected
on follow-up, there were 19 perforations during 17,672 subsequent diagnostic or therapeutic colonoscopic
examinations (107.5 per 100,000). False positive results of sigmoidoscopy, with no neoplasia identified at
subsequent diagnostic testing, were observed among 20% of men and 13% of women. Screening with flexible
sigmoidoscopy was associated with a significant decrease in colorectal-cancer incidence (in both the distal and
proximal colon) and mortality (distal colon only).
Sling Procedure for Stress Incontinence
You are considering or are scheduled for a surgical procedure called a vaginal or midurethral sling. The purpose of this procedure is to create a hammock of support and to
prevent the urethra from opening when you cough, laugh, or sneeze. The procedure
involves placing a piece of synthetic mesh (polypropylene mesh) under the urethra.
Depending on your particular symptoms and preference, the procedure can be performed
in one of two ways: just above the vagina on the lower abdomen (retropubic) or into the
groin creases (transobturator technique). Through a vaginal incision, a strip of mesh is
positioned under the urethra to create a supportive sling and to reduce or even eliminate
urinary incontinence.
A Midurethral Sling to Reduce Incontinence after Vaginal Prolapse Repair
Women without stress urinary incontinence undergoing vaginal surgery for pelvic-organ
prolapse are at risk for postoperative urinary incontinence. A midurethral sling may be placed at
the time of prolapse repair to reduce this risk. We performed a multicenter trial involving women
without symptoms of stress incontinence and with anterior prolapse (of stage 2 or higher on a
Pelvic Organ Prolapse Quantification system examination) who were planning to undergo
vaginal prolapse surgery. Women were randomly assigned to receive either a midurethral sling
or sham incisions during surgery. One primary end point was urinary incontinence or treatment
for this condition at 3 months. The second primary end point was the presence of incontinence
at 12 months, allowing for subsequent treatment for incontinence.
Adding a midurethral sling at the
time of vaginal-prolapse surgery
in women without preoperative
symptoms of stress urinary
incontinence reduces the
likelihood of urinary incontinence
at 3 and 12 months after surgery
but increases the likelihood of
adverse events. Counseling of
women who are planning to
undergo vaginal-prolapse surgery
should include attention to both
the benefits and the risks of sling
placement.
Der Begriff Hochaktive antiretrovirale Therapie, abgekürzt HAART, englisch Highly Active
Anti-Retroviral Therapy, bezeichnet eine 1996 eingeführte Kombinationstherapie aus mindestens
drei verschiedenen antiretroviralen Medikamenten (ARV) zur Behandlung der HIV-Infektion, die
unbehandelt fast immer zum Ausbruch von AIDS führt. Neuerdings wird anstatt HAART der
neutralere und damit korrektere Begriff cART (combined Anti-Retroviral Therapy) verwendet, in
Deutschland wird sie meistens nur Kombinations-Therapie oder kurz Kombi-Therapie genannt.
Zidovudin (auch Azidothymidin, kurz AZT) ist ein chemisches Derivat des Nukleosids Thymidin.
Pharmakologisch gehört es zu den nukleosidischen Reverse-Transkriptase-Inhibitoren (NRTI),
einer Gruppe antiretroviraler Substanzen. Zidovudin dient zur Behandlung HIV-1-infizierter
Patienten im Rahmen einer antiretroviralen Kombinationstherapie.
Ritonavir ist ein Arzneistoff aus der Gruppe der Proteaseinhibitoren und wird zur Therapie von
HIV-Infektionen und AIDS eingesetzt. Im Zuge einer sogenannten „highly active antiretroviral
therapy“ (HAART) wird es mit anderen Wirkstoffen (NRTI, NNRTI) kombiniert, um deren
Wirkstärke zu erhöhen.
Nevirapin bindet nicht-kompetitiv an die Reverse Transkriptase von HIV-I, nahe der
Substratbindungsstelle für Nukleoside. Dadurch wird die katalytisch aktive Bindungsstelle
blockiert. Es können nun weniger Nukleoside binden und die Polymerisation wird deutlich
verlangsamt.
Der HIV-Protease-Inhibitor Lopinavir hemmt die Weiterverarbeitung der durch das HI-Virus neu
gebildeten viralen Vorläuferproteine zu funktionstüchtigen Strukturproteinen und Enzymen und
somit die Vermehrung des Virus.
Nelfinavir (Handelsname: Viracept®, Hersteller: Hoffmann-La Roche), ist ein Arzneistoff aus der
Gruppe der HIV-Proteaseinhibitoren und wird zur Therapie von HIV-1-infizierten Patienten
eingesetzt. HIV-Proteaseinhibitoren werden im Zuge einer sogenannten „highly active
antiretroviral therapy“ (HAART) mit anderen antiviralen Wirkstoffen (NRTI, NNRTI) kombiniert.
Three Postpartum Antiretroviral Regimens to Prevent Intrapartum HIV Infection
The safety and efficacy of adding antiretroviral drugs to standard zidovudine prophylaxis in
infants of mothers with human immunodeficiency virus (HIV) infection who did not receive
antenatal antiretroviral therapy (ART) because of late identification are unclear. We evaluated
three ART regimens in such infants. Within 48 hours after their birth, we randomly assigned
formula-fed infants born to women with a peripartum diagnosis of HIV type 1 (HIV-1) infection to
one of three regimens: zidovudine for 6 weeks (zidovudine-alone group), zidovudine for 6 weeks
plus three doses of nevirapine during the first 8 days of life (two-drug group), or zidovudine for 6
weeks plus nelfinavir and lamivudine for 2 weeks (three-drug group). The primary outcome was
HIV-1 infection at 3 months in infants uninfected at birth.
Intrapartum: occurring
during labor and delivery
In neonates whose mothers did not receive ART during pregnancy, prophylaxis with a two- or
three-drug ART regimen is superior to zidovudine alone for the prevention of intrapartum HIV
transmission; the two-drug regimen has less toxicity than the three-drug regimen.
In neonates whose mothers did not receive ART during pregnancy, prophylaxis with a two- or
three-drug ART regimen is superior to zidovudine alone for the prevention of intrapartum HIV
transmission; the two-drug regimen has less toxicity than the three-drug regimen.
Nevirapine versus Ritonavir-Boosted Lopinavir for HIV-Infected Children
Nevirapine-based antiretroviral therapy is the predominant (and often the only) regimen
available for children in resource-limited settings. Nevirapine resistance after exposure to the
drug for prevention of maternal-to-child human immunodeficiency virus (HIV) transmission is
common, a problem that has led to the recommendation of ritonavir-boosted lopinavir in such
settings. Regardless of whether there has been prior exposure to nevirapine, the performance
of nevirapine versus ritonavir-boosted lopinavir in young children has not been rigorously
established. In a randomized trial conducted in six African countries and India, we compared
the initiation of HIV treatment with zidovudine, lamivudine, and either nevirapine or ritonavirboosted lopinavir in HIV-infected children 2 to 36 months of age who had no prior exposure to
nevirapine. The primary end point was virologic failure or discontinuation of treatment by study
week 24.
For infants and young children,
regardless of whether they were
previously exposed to nevirapine, we
now have evidence of the superiority
of ritonavir-boosted lopinavir–based
regimens over nevirapine-based
regimens in terms of both efficacy
and safety.
Antithrombin III (AT III) ist ein endogenes Serpin und einer der wichtigsten natürlichen
Hemmstoffe der Blutgerinnung. Es hemmt die Serinproteasen der plasmatischen Gerinnung,
baut Thrombin (Faktor IIa) proteolytisch ab und aktiviert an den Endothelzellen die Synthese des
t-PA (Plasminogenaktivator vom Gewebetyp).
Antithrombin ist der Gegenspieler des Thrombin. Es wird durch Heparin in seiner Wirksamkeit
verstärkt und beschleunigt (etwa 1000-fach). Ein Mangel an Antithrombin III kann also eine
Unwirksamkeit des Heparins oder einen hohen Heparinbedarf zur Folge haben. Nach
Operationen sinkt das AT III regelmäßig ab. Es ist daher nur eingeschränkt geeignet, eine
Verbrauchskoagulopathie nachzuweisen.
Zur Substitution wird AT III langsam intravenös verabreicht. AT III wird aus mittels Blutspende
gewonnenem menschlichen Plasmaprotein durch Fraktionierung gewonnen (Antithrombin aus
Humanplasma, hpAT) oder aus der Milch gentechnisch veränderter Säugetiere isoliert
(rekombinates humanes Antithrombin, rhAT).
Thrombosis from a Prothrombin Mutation Conveying Antithrombin
Resistance
We identified a novel mechanism of hereditary thrombosis associated with antithrombin
resistance, with a substitution of arginine for leucine at position 596 (p.Arg596Leu) in the gene
encoding prothrombin (called prothrombin Yukuhashi). The mutant prothrombin had moderately
lower activity than wild-type prothrombin in clotting assays, but the formation of thrombin–
antithrombin complex was substantially impaired. A thrombin-generation assay revealed that
the peak activity of the mutant prothrombin was fairly low, but its inactivation was extremely
slow in reconstituted plasma. The Leu596 substitution caused a gain-of-function mutation in the
prothrombin gene, resulting in resistance to antithrombin and susceptibility to thrombosis.
Genetic studies of hereditary thrombophilia have revealed two types of genetic defects: loss-offunction mutations in the natural anticoagulants antithrombin, protein C, and protein S, along
with gain-of-function mutations in procoagulant factors V (factor V Leiden) and II (prothrombin
G20210A).
Panel A shows the results of a
thrombin-generation assay of
normal plasma as well as
reconstituted plasma samples, with
recombinant prothrombins in
prothrombin-deficient plasma and
of human antithrombin (AT 50%) in
antithrombin-depleted plasma. The
heterozygous-mutant (mutanthetero) plasma contained 50%
each of wild-type and mutant
prothrombin. The table at the right
shows the total amount of thrombin
activity, which was assessed as
the area under the curve for
endogenous thrombin potential
(ETP), the maximum concentration
of thrombin (peak), and the total
duration of thrombin-generation
activity (start tail). Panel B shows
the results of a thrombingeneration assay of the respective
plasma samples after the addition
of excess antithrombin.
Human Babesiosis
Human babesiosis is an infectious disease caused by intraerythrocytic protozoa of the genus
babesia. The disease is named after Victor Babes, the Hungarian pathologist and microbiologist
who identified intraerythrocytic microorganisms as the cause of febrile hemoglobinuria in cattle in
1888. Five years later, Theobald Smith and Frederick L. Kilborne identified a tick as the vector for
transmission of Babesia bigemina in Texas cattle. This seminal observation established for the first
time that an arthropod could transmit an infectious agent to a vertebrate host.
Dark colors designate areas where human babesiosis is either endemic (solid pattern) or
sporadic, as defined by more than three tickborne cases reported in a country or state (stippled
pattern). Isolated cases of locally acquired babesiosis are depicted by circles. In the United
States, babesiosis caused by Babesia microti is endemic in the Northeast and the upper Midwest
(dark-red areas), where it is transmitted by Ixodes scapularis
The patient was born at a gestational age of 29 weeks at another hospital by cesarean section
for breech presentation, premature labor, and rupture of membranes of approximately 2 hours'
duration. He weighed 1275 g and appeared vigorous, with spontaneous respirations; the 1minute and 5-minute Apgar scores were 7 and 9, respectively. Shortly thereafter, subcostal
retractions developed. Analysis of umbilical arterial blood revealed a pH of 7.35, a partial
pressure of oxygen of 47 mm Hg, and a partial pressure of carbon dioxide of 22 mm Hg.
Continuous positive airway pressure (CPAP) was administered, and he was transferred to the
nursery. The temperature was 37.2°C under radiant heat, the blood pressure 58/44 mm Hg, the
pulse 119 beats per minute, and the oxygen saturation 94 to 96% while the patient was
breathing 50% oxygen with CPAP; the blood glucose level was 72 mg per deciliter (4.0 mmol per
liter).
On the patient's second day of life, the neonatal abstinence syndrome developed (characterized
by tremors, agitation, poor sleeping, and frantic behavior); screening of the urine for illicit drugs
was negative. Morphine was administered, resulting in improvement. Radiographs showed
improvement in the pulmonary opacities. The trachea was extubated, and nasal CPAP was
administered transiently. Results of testing conducted by the Massachusetts newborn screening
program were normal. Culture of blood drawn on admission was sterile, and the administration
of antibiotic agents was stopped.
Panel C (hematoxylin and eosin) shows adrenal
cortical infarcts (arrow), with viral inclusions in
adjacent cells (inset). Immunohistochemical
analysis of a specimen of the lung for HSV-1 and
HSV-2 (Panel D and inset, immunoperoxidase
stain for HSV-1 and HSV-2) shows staining of
the cells that have inclusions. I reported the
results of the postmortem examination to the
mother and suggested that she be checked for
HSV infection. She went to the clinic, asking to
be checked for herpes. Serologic samples were
drawn, but a physical examination was not
performed, so we do not know whether she had
a current lesion. She now seems to be doing
well emotionally.
Ultrasound-Guided Peripheral IV Placement
Suicide mortality in India: a nationally representative survey
WHO estimates that about 170 000 deaths by suicide occur in India every year, but few
epidemiological studies of suicide have been done in the country. We aimed to quantify suicide
mortality in India in 2010. The Registrar General of India implemented a nationally representative
mortality survey to determine the cause of deaths occurring between 2001 and 2003 in 1·1
million homes in 6671 small areas chosen randomly from all parts of India. As part of this survey,
fieldworkers obtained information about cause of death and risk factors for suicide from close
associates or relatives of the deceased individual. Two of 140 trained physicians were randomly
allocated (stratified only by their ability to read the local language in which each survey was
done) to independently and anonymously assign a cause to each death on the basis of electronic
field reports. We then applied the age-specific and sex-specific proportion of suicide deaths in
this survey to the 2010 UN estimates of absolute numbers of deaths in India to estimate the
number of suicide deaths in India in 2010.
The underlying cause of each death was sought by an enhanced form of verbal autopsy, known as the routine,
reliable, representative, re-sampled household investigation of mortality with medical evaluation (RHIME). The
RHIME method is a structured investigation of events before the death, including a written report in the local
language of the household.
Poisoning, mostly from pesticides (mainly
organophosphates) used in agriculture, was the leading
method of suicide in both men and women,
corresponding to about 92 000 deaths nationally in
individuals 15 years or older (figure 3). More than half
(679) of the 1276 poisonings in the 2001—03 survey
were classifiable (ICD-10 codes X60—X68) and 579
were unclassifiable (X69). Of classifiable poisonings,
the vast majority (535) were from pesticide poisoning
(X68).
Suicide death rates in India are among the highest in the world. A large proportion of adult suicide
deaths occur between the ages of 15 years and 29 years, especially in women. Public health
interventions such as restrictions in access to pesticides might prevent many suicide deaths in
India.
The benefits and harms of intravenous thrombolysis with recombinant tissue
plasminogen activator within 6 h of acute ischaemic stroke (the third
international stroke trial [IST-3]): a randomised controlled trial
Thrombolysis is of net benefit in patients with
acute ischaemic stroke, who are younger than
80 years of age and are treated within 4·5 h of
onset. The third International Stroke Trial (IST-3)
sought to determine whether a wider range of
patients might benefit up to 6 h from stroke
onset. In this international, multicentre,
randomised, open-treatment trial, patients were
allocated to 0·9 mg/kg intravenous recombinant
tissue plasminogen activator (rt-PA) or to
control. The primary analysis was of the
proportion of patients alive and independent, as
defined by an Oxford Handicap Score (OHS) of
0—2 at 6 months. they had symp-toms and
signs of clinically definite acute stroke; the time
of stroke onset was known; treatment could be
started within 6 h of onset; and CT or MRI had
reliably excluded both intracranial haemorrhage
and structural brain lesions.
Outcome at 6 months: Oxford Handicap Scale (OHS) by
treatment group
For the types of patient recruited in IST-3,
despite the early hazards, thrombolysis within 6
h improved functional outcome. Benefit did not
seem to be diminished in elderly patients. More
deaths occurred within 7 days in the rt-PA group
(163 [11%]) than in the control group (107 [7%].
Fatal or non-fatal symptomatic intracranial
haemorrhage within 7 days occurred in 104 (7%)
patients in the rt-PA group versus 16 (1%) in the
control group.
Recombinant tissue plasminogen activator for acute ischaemic stroke: an
updated systematic review and meta-analysis
Recombinant tissue plasminogen activator (rt-PA, alteplase) improved functional outcome in
patients treated soon after acute ischaemic stroke in randomised trials, but licensing is
restrictive and use varies widely. The IST-3 trial adds substantial new data. We therefore
assessed all the evidence from randomised trials for rt-PA in acute ischaemic stroke in an
updated systematic review and meta-analysis. We searched for randomised trials of
intravenous rt-PA versus control given within 6 h of onset of acute ischaemic stroke up to
March 30, 2012. We estimated summary odds ratios (ORs) and 95% CI in the primary analysis
for prespecified outcomes within 7 days and at the final follow-up of all patients treated up to 6
h after stroke.
The evidence indicates that intravenous rt-PA
increased the proportion of patients who were
alive with favourable outcome and alive and
independent at final follow-up. The data
strengthen previous evidence to treat patients as
early as possible after acute ischaemic stroke,
although some patients might benefit up to 6 h
after stroke.
Self-harm and suicide in adolescents
Self-harm and suicide are major public health problems in adolescents, with rates of selfharm being high in the teenage years and suicide being the second most common cause
of death in young people worldwide. Important contributors to self-harm and suicide
include genetic vulnerability and psychiatric, psychological, familial, social, and cultural
factors. The effects of media and contagion are also important, with the internet having an
important contemporary role. Prevention of self-harm and suicide needs both universal
measures aimed at young people in general and targeted initiatives focused on high-risk
groups. There is little evidence of effectiveness of either psychosocial or pharmacological
treatment, with particular controversy surrounding the usefulness of antidepressants.
Restriction of access to means for suicide is important. Major challenges include the
development of greater understanding of the factors that contribute to self-harm and
suicide in young people, especially mechanisms underlying contagion and the effect of
new media. The identification of successful prevention initiatives aimed at young people
and those at especially high risk, and the establishment of effective treatments for those
who self-harm, are paramount needs.
Suicide in young men
Suicide is second to only accidental death as the leading cause of mortality in young men
across the world. Although suicide rates for young men have fallen in some high-income and
middle-income countries since the 1990s, wider mortality measures indicate that rates remain
high in specific regions, ethnic groups, and socioeconomic groups within those nations where
rates have fallen, and that young men account for a substantial proportion of the economic cost
of suicide. High-lethality methods of suicide are preferred by young men: hanging and firearms
in high-income countries, pesticide poisoning in the Indian subcontinent, and charcoal-burning
in east Asia. Risk factors for young men include psychiatric illness, substance misuse, lower
socioeconomic status, rural residence, and single marital status. Population-level factors
include unemployment, social deprivation, and media reporting of suicide. Few interventions to
reduce suicides in young men have been assessed. Efforts to change help-seeking behaviour
and to restrict access to frequently used methods hold the most promise.
Population-level factors shown to affect
rates of suicide in young men in
specified parts of the world include
unemployment, social deprivation, and
the media's reporting of suicide. This
review underlines the importance of the
development of regionally and
nationally tailored approaches to
reducing suicide, and remaining
abreast of key mortality indicators to
identify the groups at highest risk of
premature death.
Means restriction for suicide prevention
Limitation of access to lethal methods used for suicide—so-called means restriction—is an
important population strategy for suicide prevention. Many empirical studies have shown that such
means restriction is effective. Although some individuals might seek other methods, many do not;
when they do, the means chosen are less lethal and are associated with fewer deaths than when
more dangerous ones are available. We examine how the spread of information about suicide
methods through formal and informal media potentially affects the choices that people make when
attempting to kill themselves. We also discuss the challenges associated with implementation of
means restriction and whether numbers of deaths by suicide are reduced.
Hanging, jumping from heights (particularly from individuals’ own apartments or houses), and fatal
shooting with firearms in countries with relatively non-restrictive gun laws such as the USA cannot
be readily restricted.
The Media: For example, the media introduced and quickly disseminated reports on the burning of
charcoal in a confined space in Hong Kong and Taiwan, which then rapidly increased and spread to
other Asian regions in the late 1990s.
The increased use of pesticides during the second half of the 20th century was associated with an
increase in suicides in many agrarian societies.
A 19-year-old woman from a rural village, with poor education and very limited income, presented
to our dermatology clinic in Phnom Penh. She complained of persistent blue and brown patches
on her skin, bleeding gums, lethargy, and malaise. The patient denied any physical trauma,
insect bites, or general diseases. Medical history was unremarkable. Examination of the skin
showed numerous ecchymotic patches with diameters between 1 cm and 5 cm; the colour range
was dark blue, brown, green, and yellow. There were also many perifollicular purpuric petechiae
Petechiae were also seen on the
buccal mucosa, particularly on the
frontal upper and lower gums; these
lesions were friable and bled easily.
No other abnormalities were found on
general clinical examination, in
particular no hyperkeratosis and no
oedema. Further questioning of our
patient revealed a diet consisting
mainly of rice and dried fish with an
almost complete absence of
vegetables and fruits.
Measurement of the ascorbic acid concentration is usually not helpful to ascertain a diagnosis of
scurvy because values tend to reflect recent intake rather than actual tissue stores of vitamin C.
Typical symptoms, along with a history of dietary deficiency of vitamin C, are usually sufficient to
establish the diagnosis. Nevertheless, guidelines suggest that a fasting serum vitamin C
concentration above 34·1 µmol/L rules out scurvy and those less than 11·4 µmol/L show
deficiency.
Die meisten Symptome des Skorbut gehen auf die fehlerhafte Biosynthese des Kollagens
zurück. Vitamin C ist ein wichtiger Cofaktor bei der Modifizierung der Aminosäuren Prolin und
Lysin zu Hydroxyprolin und Hydroxylysin (Hydroxylierung). Bei fehlender Hydroxylierung
werden nur schadhafte Kollagenmoleküle gebildet, die ihrer Funktion als Strukturprotein nicht
nachkommen können. Die bei schwerem Skorbut auftretende Depression hingegen könnte mit
der gestörten Bildung von Noradrenalin, sekundär Adrenalin sowie Serotonin
zusammenhängen, da deren Synthese durch die Dopamin-β-Hydroxylase (im Falle des
(Nor-)Adrenalins) Vitamin-C-abhängig erfolgt. In Röntgenaufnahmen zeigen sich deutliche
Abhebungen der Knochenhaut durch Blutungen (subperiostale Hämorrhagien), besonders an
den Metaphysen. Bei Kindern und Jugendlichen sind die Wachstumsfugen verbreitert und
unregelmäßig, oft mit einer zusätzlichen weißen Linie metaphysär (Frankl-Linie) und einer
hypodensen „Trümmerfeld“-Zone darunter, die sog. „Skorbut-Linie“. Das Knochenalter ist meist
ein oder zwei Jahre hinter dem biologischen Alter zurück
Vitamin C ist ein Radikalfänger und hat eine antioxidative Wirkung (es wirkt also als
Reduktionsmittel). Weiterhin stellt Vitamin C ein wichtiges Coenzym für die Prolyl-4-Hydroxylase
dar. Dieses Enzym wird bei der Biosynthese des Proteins (Eiweißes) Kollagen benötigt. Es
wandelt integrierte Prolinreste in 4-Hydroxyprolyl-Seitenketten unter Verbrauch von molekularem
Sauerstoff um. Hydroxyprolin ist für den stabilen Kollagenaufbau unerlässlich. Ebenfalls innerhalb
der Biosynthese von Kollagen, aber auch weiterer Proteine, findet mithilfe von Ascorbinsäure und
des Enzyms Lysylhydroxylase die Hydroxylierung von L-Lysin zum Hydroxylysin statt. Im
Kollagen erfüllt dieses eine Funktion in der kovalenten Quervernetzung benachbarter Moleküle.
Darüber hinaus kann Hydroxylysin im Kollagen und weiteren Proteinen glykosyliert werden, was
zur Bildung von Glykoproteinen führt.
Mangel an Vitamin C führt zu einer verminderten Aktivität der Prolyl-Hydroxylierung und der LysylHydroxylierung und damit zur Instabilität von Kollagen (Ehlers-Danlos-Syndrom). Da Kollagen in
praktisch allen Organen und Geweben des menschlichen und tierischen Organismus vorkommt,
vor allem aber im Bindegewebe, wird bei Mangel von Vitamin C Skorbut ausgelöst. Auch bei der
Hydroxylierung von Steroiden ist Vitamin C ein wichtiger Cofaktor. Darüber hinaus spielt es eine
wichtige Rolle beim Aufbau von Aminosäuren wie beispielsweise dem L-Tyrosin. Auch bei der
Umwandlung von Dopamin zu Noradrenalin, im Cholesterin-Stoffwechsel und bei der
Carnitinbiosynthese wird Ascorbinsäure benötigt. Mit Niacin und Vitamin B6 steuert Vitamin C die
Produktion von L-Carnitin, das für die Fettverbrennung in der Muskulatur benötigt wird. Weiterhin
begünstigt es die Eisenresorption im Dünndarm.