| dc.contributor.author | Polesie, Sam | |
| dc.date.accessioned | 2019-09-06T07:36:45Z | |
| dc.date.available | 2019-09-06T07:36:45Z | |
| dc.date.issued | 2019-09-06 | |
| dc.identifier.isbn | 978-91-7833-454-4 (PRINT) | |
| dc.identifier.isbn | 978-91-7833-455-1 (PDF) | |
| dc.identifier.uri | http://hdl.handle.net/2077/60781 | |
| dc.description.abstract | Methotrexate (MTX) is an anti-inflammatory
and immunosuppressive drug commonly
used to treat psoriasis, psoriatic arthritis
and rheumatoid arthritis. Cutaneous
malignant melanoma (CMM) is a common
and dangerous type of skin cancer and in
recent decades a noteworthy increase in
incidence has been observed. In Sweden,
CMM is the fifth most common form of
cancer in both men and women. This type
of cancer is more frequent among patients
with an impaired immune system such as
organ transplant recipients (OTRs) who are
treated with immunosuppressive drugs to
prevent rejection of the transplanted organ.
The use of MTX, has previously been associated
with an increased risk of CMM in an
Australian investigation.
The purpose of this thesis was to study the
association between MTX and the risk of
CMM.
In Paper I, a retrospective comparative cohort
study was conducted, comprising all
Swedish individuals over 18 years with at
least one filled MTX prescription in the
time period 2005-2014 (MTX-exposed).
For each MTX-exposed patient, five ageand
sex-matched MTX-unexposed individuals
were selected (MTX-unexposed). The
risk of CMM was elevated among MTX-exposed
subjects, but this risk increase was
lower than previously observed and hardly
relevant in clinical practice.
To further investigate a possible association
between MTX and CMM, a dose-response
analysis was performed. Paper II used the cohort
above and analyzed whether increased
MTX doses elevated the risk. In summary,
no conclusive dose-response relationship
between MTX and CMM was observed.
Paper III investigated whether CMM that
occurred in MTX-exposed patients caused
an increased mortality compared to CMM
occurring among the MTX-unexposed individuals.
MTX-exposed patients had an
increased risk of melanoma mortality. This
observation was robust, after adjusting for
melanoma stage at diagnosis.
Paper IV investigated patients who had already
had CMM and exposed to MTX after
the first CMM diagnosis. The risk of a
new CMM among these patients was not
increased compared to a corresponding
MTX-unexposed group.
Paper V was performed using individuals
from a cohort of psoriasis patients. Previously
cancer-free psoriasis patients who
developed CMM and psoriasis patients who
had not developed CMM at the corresponding
date were compared. The proportion exposed to MTX in each group did not differ
significantly.
In Paper VI, the dermoscopic appearance of
CMM that occurred in OTRs was investigated.
The melanoma-specific features
in this group were compared to age- and
sex-matched controls. When analyzing the
results, no differences could be observed.
Nevertheless, these results are limited due
to a small sample size and should instead be
regarded as an invitation to more investigations.
In conclusion, this thesis has shown that
CMM is unlikely to be associated with the
use of MTX and the dermoscopic appearance
of CMM in immunosuppressed patients
does not seem to differ from those of
immunocompetent individuals. | sv |
| dc.language.iso | eng | sv |
| dc.relation.haspart | I Polesie S, Gillstedt M, Sönnergren HH, Osmancevic A, Paoli J. Methotrexate treatment and risk for cutaneous malignant melanoma: a retrospective comparative registry-based cohort study. Br J Dermatol. 2017 Jun;176(6):1492-1499. ::PMID::27858996 | sv |
| dc.relation.haspart | II Polesie S, Gillstedt M, Paoli J, Osmancevic A.
Methotrexate Exposure and Risk of Cutaneous Malignant Melanoma: No Evidence of a Dose-response Relationship. Acta Derm Venereol. 2018 Oct 10;98(9):888-895. ::PMID::29972216 | sv |
| dc.relation.haspart | III Polesie S, Gillstedt M, Paoli J, Osmancevic A.
Methotrexate and melanoma-specific mortality.
J Eur Acad Dermatol Venereol. 2019 Mar;
33(3):e123-e125 Oct 25. ::PMID::30357928 | sv |
| dc.relation.haspart | IV Polesie S, Gillstedt M, Paoli J, Osmancevic A.
Methotrexate treatment in patients with a history of cutaneous melanoma and the risk of a consecutive primary melanoma: A national retrospective registry-based cohort study. J Am Acad Dermatol. 2017 Jul;77(1):161-163 ::PMID::28619553 | sv |
| dc.relation.haspart | V Polesie S, Gillstedt M, Paoli J, Osmancevic A.
Methotrexate treatment for psoriasis patients and risk of cutaneous melanoma: a nested case-control study. In manuscript (submitted) | sv |
| dc.relation.haspart | VI Polesie S, Gillstedt M, Zaar O, Osmancevic A, Paoli J. Dermoscopic Features of Melanomas in Organ Transplant Recipients. Acta Derm Venereol. 2019 Jul 12. [Epub ahead of print]. ::PMID::31304556 | sv |
| dc.subject | methotrexate | sv |
| dc.subject | cutaneous melanoma | sv |
| dc.subject | risk | sv |
| dc.subject | organ transplant recipients | sv |
| dc.subject | dermoscopy | sv |
| dc.title | Methotrexate and Risk of Cutaneous Melanoma | sv |
| dc.type | text | eng |
| dc.type.svep | Doctoral thesis | eng |
| dc.gup.mail | sam.polesie@vgregion.se | sv |
| dc.type.degree | Doctor of Philosophy (Medicine) | sv |
| dc.gup.origin | University of Gothenburg. Sahlgrenska Academy | sv |
| dc.gup.department | Institute of Clinical Sciences. Department of Dermatology and Venereology | sv |
| dc.gup.defenceplace | Torsdagen den 5 december 2019, kl. 09.00, hudklinikens föreläsningssal, Gröna stråket 16, Sahlgrenska universitetssjukhus/Sahlgrenska, Göteborg | sv |
| dc.gup.defencedate | 2019-12-05 | |
| dc.gup.dissdb-fakultet | SA | |
