International Journal of Research in Dermatology | October-December 2018 | Vol 4 | Issue 4 Page 605
International Journal of Research in Dermatology
Tammaro A et al. Int J Res Dermatol. 2018 Nov;4(4):605-606
Iron-deficiency and pruritus: a possible explanation
of their relationship
Antonella Tammaro1*, Camilla Chello1, Marco di Fraia1, Domenico Giordano1,
Francesca Magri1, Verdiana Zollo1, Francesca Romana Parisella2, Gabriella De Marco1
Itching is an unpleasant sensation related to a skin
eruption or irritation that frequently provokes scratching.
In contrast, generalized idiopathic pruritus is often not
associated with a primary elementary skin lesion. Most
importantly, generalized pruritus can represent the
manifestation of a systemic disease. Some studies report
that 14–50% of pruritic patients without a clear
dermatologic cause have an underlying internal cause for
their symptom, among which iron deficiency may act an
A 47-year-old woman was referred for a three-year
history of generalized pruritus associated to scratching
lesions of the trunk that had recently become more
severe. She had been treated with several antihistamine
drugs, with slight benefit. There was no familial or
personal history of atopy. The skin was normal except for
some scratch marks, the rest of the physical examination
was unremarkable. Laboratory examinations were all in
the normal range, except for low haemoglobin (9.6 g/dl),
serum iron (14 mg/dl) and ferritin (3.19 ng/ml) levels.
Her personal history was positive for atrophic gastritis
without Helicobacter pylori infection. A thorough search
was made to determine the cause for iron deficiency
anemia: peripheral blood smear showed microcythemia
and hypochromia; autoimmunity screening and
gastroesophageal endoscopy evaluation were negative for
celiac disease; also a bone marrow examination did not
show abnormalities due to iron deficiency. In addition,
we performed examinations to exclude diseases inducing
generalized itching. The total serum IgE levels were
normal; repeated test for occult blood and parasitic
infestation produced negative results; liver and renal
function tests, thyroid enzymes, copper serum and
Pruritus of unknown origin is defined as itching lasting for more than 3 weeks without a clear identifiable cause.
Aetiology of itching is wide ranging and includes chronic renal failure, cholestasis and internal malignancy. Iron
deficiency has been described to be causative of pruritus but the mechanism underlying this association remains
unclear. We report the case of a female patient with iron deficiency anemia and generalized pruritus, resolved after
intravenous administration of iron-complex supplements and we explained a possible mechanism between this
Keywords: Itch, Iron Deficiency, Anemia
1Department of NESMOS, Dermatology Unit, Sant’Andrea Hospital, Faculty of Medicine and Psychology University
of Rome “Sapienza”, Italy
2Faculty of Medicine, Towson University, Towson City, Maryland, USA
Received: 15 May 2018
Revised: 11 July 2018
Accepted: 19 July 2018
Dr. Antonella Tammaro,
Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under
the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial
use, distribution, and reproduction in any medium, provided the original work is properly cited.
Tammaro A et al. Int J Res Dermatol. 2018 Nov;4(4):605-606
International Journal of Research in Dermatology | October-December 2018 | Vol 4 | Issue 4 Page 606
immunoglobulin levels were in the normal range and
patch test to exclude contact allergy dermatitis was
Treatment was started with administration of iron-
complex supplements alone (5 ml/day for ten days); after
only two days of treatment, the patient referred an
improvement of hitching that completely disappeared at
the end of iron therapy.
Iron deficiency is reported to produce symptoms
unrelated to anemia, including headache, irritability,
exercise intolerance, hair thinning, soreness or burning of
the tongue, angular cheilitis, koilonychia, pica,
disturbances of gastrointestinal function, dysphagia,
chronic fatigue and muscular weakness.2
Iron deficiency appear also to be associated with an
abnormal T lymphocytes composition and therefore an
increased susceptibility to infection.3,4
The association of iron deficiency and pruritus has been
observed and studied as early as the 60s and in 1974
Vickers described the relationship of iron deficiency
generalized pruritus in 87 patients, but few data in
literature are reported to explain how low serum iron
levels can cause itching.5,6
It is well known that iron is a major constituent of several
tissue compounds, usually classified in: haem iron
compounds (contained in cytochromes, myoglobin,
catalase and peroxidase); iron-sulphur proteins and
metalloproteins; compounds requiring iron as a cofactor.7
Finally, there are some enzymes that are presumed to
contain iron, such as ribonucleotide reductase, involved
in DNA synthesis. Recently, it was also demonstrated
that iron deficiency had a pronounced negative effect on
elastic fibers development, downregulating the
expression of genes encoding fibrillin 1 and 3 that are
essential for the normal elastic fibers assembly.3,8
These data induced us to hypothesize that iron deficiency
could lead to a decreased synthesis of DNA with
consequent reduction of cutaneous cell turnover and
thinning of the skin. In addition, low iron serum levels
could affect the correct assembly of dermal elastic fibers,
with a consequent reduced skin elasticity. These features
can presumably be the basis of cutaneous xerosis, which
is already a well-known cause of itching symptoms.
We reported this interesting case to highlight how the
itching is a symptom that has not to be underestimated
because it can be light of underlying systemic diseases.
Funding: No funding sources
Conflict of interest: None declared
Ethical approval: Not required
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Cite this article as: Tammaro A, Chello C, Fraia
MD, Giordano D, Magri F, Zollo V. Iron-deficiency
and pruritus: a possible explanation of their
relationship. Int J Res Dermatol 2018;4:605-6.