Expert: Ivan Goldberg, M.D. - 11/24/2009

Question
I read a two year old article in which you mentioned a connection between lithium and psoriatic arthritis. Is the psoriasis or the lithium that is the cause of the arthritis? Do you know of any studies that identify this link?

http://en.allexperts.com/q/Bipolar-Disorder-2192/Lithium-Related-Psoriosis.htm

Answer
Psoriasis is a skin disease that is sometimes complicated by arthritis. The arthritis can be quite severe and crippling. Psoriasis is made induced or exacerbated by lithium treatment. The situation is especially difficult since in many instances, when lithium exacerbates psoriasis (and possibly psoriatic arthritis) these conditions progress even if the lithium is discontinued. Below are a few abstracts on the subject.

Best regards . . .

Ivan
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1. Arch Dermatol Res. 2006 Dec;298(7):309-19. Epub 2006 Oct 5.

The importance of disease associations and concomitant therapy for the long-term
management of psoriasis patients.

Mrowietz U, Elder JT, Barker J.

Department of Dermatology, University of Kiel, Schittenhelmstrasse 7, 24105 Kiel,
Germany. umrowietz@dermatology.uni-kiel.de

It is well established that several inflammatory-type conditions, such as
arthritis, diabetes, cardiovascular disease, and irritable bowel disease exist
comorbidly and at an increased incidence in patients with psoriasis. Psoriasis
and other associated diseases are thought to share common inflammatory pathways.
Conditions such as these, with similar pathogenic mechanisms involving cytokine
dysregulation, are referred to as immune-mediated inflammatory diseases (IMIDs).
Considerable evidence for the genetic basis of comorbidities in psoriasis exists.
The WHO has reported that the occurrence of chronic diseases, including IMIDs,
are a rising global burden. In addition, conditions linked with psoriasis have
been associated with increasing rates of considerable morbidity and mortality.
The presence of comorbid conditions in psoriasis patients has important
implications for clinical management. QoL, direct health care expenditures and
pharmacokinetics of concomitant therapies are impacted by the presence of
comorbid conditions. For example, methotrexate is contraindicated in hepatic
impairment, while patients on cyclosporin should be monitored for kidney
function. In addition, some agents, such as beta blockers, lithium, synthetic
antimalarial drugs, NSAIDs and tetracycline antibiotics, have been implicated in
the initiation or exacerbation of psoriasis. Consequently, collaboration between
physicians in different specialties is essential to ensuring that psoriasis
treatment benefits the patient without exacerbating associated conditions.

PMCID: 1705513
PMID: 17021761 [PubMed - indexed for MEDLINE]


2. Adv Exp Med Biol. 1999;455:221-5.

Triggered psoriasis.

Wolf R, Ruocco V.

Department of Dermatology, Tel-Aviv Sourasky Medical Center, Ichilov Hospital,
Israel. wolf_r@netvision.net.il

There are conflicting reports in the literature concerning the use of
antimalarials in psoriatic patients with arthropathy or coexisting systemic lupus
erythematosus. On the basis of a review of 18 publications in English, it was
estimated that up to 18% of patients with psoriasis would develop an exacerbation
of their disease following antimalarial therapy. In contrast to lithium and
beta-blockers, antimalarials do not induce psoriasis de novo, but they only
trigger already existing psoriasis, via a pharmacologic mechanism, probably due
to an alteration of the activity of enzymes involved in the epidermal
proliferation process. The chemical structure of the antimalarials is very
similar to dansylputrescine, a potent transglutaminase (TGase) inhibitor. We
suggested therefore that antimalarials trigger psoriasis through the modulation
of the TGase activity. To verify this hypothesis, we examined the effect of
hydroxychoroquine sulphate (HCQS) on cultured human skin and on TGase activity in
vitro. Significant changes of epidermal morphology were seen in all explants
cultured in the presence of HCQS. HCQS showed a concentration-dependent
inhibition of TGase activity. We suggest that HCQS caused an initial break in the
barrier function of the epidermis by inhibiting TGase activity; this was followed
by a physiologic response of the epidermis aimed at barrier restoration. This
rather non-specific stimulus to epidermal proliferation is probably sufficient to
trigger psoriasis in predisposed individuals. Drug eruption is an age-old but
timeless and fascinating subject. Of particular interest are those drug eruptions
that may mimic idiopathic skin diseases. Apart from their obvious practical
importance they are also of theoretical interest, because they provide an
opportunity to investigate possible pathogenic mechanisms of the mimicked
disease. In this paper, I would like to review briefly the characteristics of
drug-induced psoriasis, and then propose a hypothesis concerning the pathogenesis
of this phenomenon. In all, we found 258 reported cases of drug-induced psoriasis
[1]. The drugs mainly involved are the antimalarials, lithium, beta blockers, and
a large group of miscellaneous drugs. Three out of the four groups of drugs
(lithium, beta blockers and miscellaneous drugs) can both induce or trigger
psoriasis with almost equal frequency, namely they induce psoriasis de novo or
they exacerbate an already existing psoriasis in 30-50% of the reported cases.
Only one group of drugs, the antimalarials is an exception. In contrast to
lithium and beta blockers, antimalarials do not induce psoriasis de novo, but
only trigger already existing psoriasis. There are only three reported cases of
psoriasis induced by antimalarials in patients who did not have the disease
previously. Of these three patients, one had a seronegative arthritis and a
family history of psoriasis, and, as stated by the author, there is evidence that
the patient had pre-existing latent psoriasis. We believe that the other two
cases may also have had latent psoriasis. That antimalarial drugs only trigger
latent psoriasis and do not induce psoriasis de novo can be suspected from the
fact that psoriasis cleared up completely after withdrawal of the drug in only
30% of patients on antimalarials, as compared with more than 60% of those
receiving lithium and nearly 50% of those receiving beta blockers. This is
probably also why the incubation period of the cases induced by antimalarial
drugs is much shorter than that of lithium and beta blockers. Possibly, in
triggered psoriasis (as in antimalarials) the drug only sets off with a chain of
pathologic events previously programmed and ready to be set off, whereas in true
drug-induced cases (as in some cases of lithium and betablockers) the drug is
supposed to cause more profound changes and, therefore, more time is needed for
these changes to occur.

PMID: 10599347 [PubMed - indexed for MEDLINE]


3. Aust N Z J Psychiatry. 1987 Dec;21(4):601-4.

Psoriatic arthritis during lithium therapy.

Skerritt PW.

Department of Psychiatry, Royal Perth Hospital, WA.

A case is presented of psoriasis occurring de novo during lithium therapy and
progressing to psoriatic arthritis. Exacerbation of pre-existing psoriasis during
lithium treatment has often been described, as has the disease occurring de novo.
This would seem to be the first description of psoriatic arthritis apparently
related to lithium.

PMID: 3130043 [PubMed - indexed for MEDLINE]


4. J Invest Dermatol. 1980 Feb;74(2):81-4.

Increased granulocyte adherence in psoriasis and psoriatic arthritis.

Sedgwick JB, Bergstresser PR, Hurd ER.

Circulating polymorphonuclear leukocytes (PMN) from patients with psoriasis and
psoriatic arthritis were found to be significantly more adherent to nylon fiber
columns when compared with both normal and nonpsoriatic patient control groups.
The increased adherence correlated positively with the extent of disease and was
highest in those patients with psoriatic arthritis. Total leukocyte and PMN
counts were increased in psoriasis patients and were highest in the psoriatic
arthritis group. No increase in cell counts was found for mononuclear leukocytes.
PMN adherence was not increased in lithium-treated patients or a nonpsoriatic
patient control group although such patients did have significant granulocytosis.
PMN's are frequently present in lesions of psoriasis as are activated complement
components and abnormal keratinocyte cyclic nucleotide levels. These factors or
others may cause a generalized activation of PMN's in psoriasis leading to
migration of neutrophils into the skin lesion. The present study demonstrates a
systemic effector cell alteration in psoriasis and contradicts the general
concept that uncomplicated psoriasis is limited to the skin.

PMID: 7351502 [PubMed - indexed for MEDLINE]