healthmedicinet

A 35 year old woman with a history of intermittent rhinitis presented with a 5 day
history of urticaria, fever, headaches, myalgia and arthralgia. She developed hives
and erythematous maculae in her trunk, back, abdomen and limbs (Figures 1, 2); they were pruriginous and painful, with a burning sensation, and had more than
1 cm in diameter. The lesions lasted more than 24 hours, altering the pigmentation
of the area. Angioedema was present in hands, fingers, ankles and feet, and left no
pitting.

Figure 1. Wheals and erythematous maculae in trunk, back and abdomen were found.

Figure 2. Wheals and erythematous maculae also can be found in ankle.

Severe headaches and myalgia impaired the patient’s ability to conduct her daily routine
and fever spiked as high a 39.5 C.

The patient had been taking OTC diet pills eighteen days before, and six days previously
consulted for dehydration and violaceous hives in her palms; after that she suspended
the pills.

Physical examination revealed large confluent areas of wheals and maculae in her trunk,
limbs and abdomen, scored 6/10 in intensity of the pruritus by the patient, whom also
complained of muscular pain. The rest of the examination was unremarkable. She had
a normal hemoglobin concentration and lymphopenia. The C-reactive protein concentration
was 7.5 mg/L (normally 5 mg/L); complement components, liver function test, urea
and creatinine, plasma sodium, glucose and thyroid hormones and antibodies were within
normal ranges. Antinuclear antibodies (ANA) were not detectable in blood.

The skin biopsy of one lesion was performed, in which a slight alteration of vacuolar
interface was observed, the papillary dermis presented edema and there was a moderate
superficial and perivascular infiltrate of lymphocytes and eosinophils with focal
fibrin deposits in blood vessel walls and extravasation of erythrocytes. After confirmation
of the diagnosis of UV, the patient was prescribed with oral corticosteroids and antihistamines,
achieving rash remission. Due to persistence of headaches, fever and myalgia, hydroxychloroquine
was added to the treatment, with remission of all the symptoms one month later.

Discussion about UV

UV is a condition that usually presents itself with wheals in the proximal areas of
the limbs and in the trunk, often more painful than pruriginous, with a duration of
symptoms of more than 24 hours, a violaceous shade to the lesions, and residual pigmentation
after resolution 4]. Two forms have been described: hypo-complementemic UV and normo-complementemic UV.
The hypo-complementemic form may as well manifest with or without systemic symptoms
2].

UV is in most of the cases idiopathic, but there is a wide variety of conditions,
such as infections, hematologic disorders, physical urticaria, exercise, drugs, etc.,
that have been associated with this disease. The most commonly linked disorders are
connective tissue diseases, particularly SLE and Sjögren’s syndrome. UV is thought
to represent a type III hypersensitivity reaction due to the circulation immune complexes
that may be found in up to 75% of patients 5].

UV lesions damage the capillary and post-capillary venules. Histopathological findings
include perivascular neutrophilic or lymphocytic infiltrates with fibrinoid necrosis,
evidence of fully developed leukocytoclastic vasculitis with injury and swelling of
the nuclei of endothelial cells of postcalpillary venules and extravasation of erythrocytes
6].

Lymphocytes can predominate or be the only cell observed in older vasculitic lesions.
Fibrinoid changes or necrosis and particularly thrombosis are less common in UV than
in the fully developed lesions of palpable purpura. There is usually little vessel
wall disruption and only a mild degree of perivascular infiltrate, without red blood
cell extravasation, in young UV lesions. Such lesions can be difficult to distinguish
from true urticarial 2].

In our case report, the ingredients in the OTC diet pills were: synephrine HCL, synthetic
99% guggulsterones, thyroid stimulating matrix, Yohimbine HCL and phenylamine.

The unregulated use of synephrine in dietary supplements is arising controversy in
the scientific community, namely regarding to its safety and efficacy when it is used
in weight-loss products 7]. It is well known that the occurrence of severe cardiovascular toxicity related to
the consumption of synephrine-containing products determined the temporary prohibition
of synephrine in dietary products in Canada 8].

Yohimbine substantially increases the incidence of adverse drug side effects such
as: gastrointestinal discomfort (46%), tachycardia (43%), anxiety/agitation (33%),
and hypertension (25%). Yohimbine exposures were associated with a significantly higher
number of severe adverse reactions to drugs, and were more likely to require management
at a health-care facility (odds ratios [95% CIs] were 5.81 [4.43 to 7.64] and 2.35
[1.82 to 3.04], respectively 9]. Guggulsterones have been associated with fulminant hepatic failure, requiring emergency
liver transplants 10].

Although all of these ingredients have reported adverse side effect, this may be the
first report of them inducing vasculitis. We believe that the development of UV might
have been induced by the use of diet OTC pills, based on the temporal relationship
between the intake of the pills and the appearance of the dermatological lesions and
systemic manifestations in the lack of another trigger. The histologically proven
vasculitis and finally the reversal of the clinical signs after discontinuation of
the OTC diet pills also suggest an association.

UV is a manifestation of inflammatory injury of capillaries and post-capillary venules
in the skin. The ingredients found in these OTC diet pills have the capacity of inducing
IgG antibodies against the collagen-similar regions of C1q to form immune complexes,
initiating an inflammatory cascade that leads to mast cell degranulation. The substances
released thereby result in increased vascular permeability causing urticaria and/or
angioedema 2].

In our center, we have seen several patients who were using the same diet pills and
developed urticaria, but ethical considerations prevent the conduction of a challenge
test to confirm the association, due to the unpredictability of side effects that
may occur on patients.