Psoriasis in the transplant population

Abstract

Solid organ and stem cell transplants are increasingly common, and dermatologists will more frequently encounter and need to manage common skin diseases, such as psoriasis, in transplant patients. This review explores psoriasis remission and occurrence in recipients of solid organ and stem cell transplants. Hematopoietic and mesenchymal stem cell transplants may show potential for treating psoriasis in patients with leukemia or who have other medical conditions requiring stem cell transplant. The effects of solid organ transplant are less clear, partly due to limitations in the breadth of the literature. De novo psoriasis has been reported in recipients of solid organ transplants, but the reasons for this development have yet to be fully understood. Overall, the literature on this subject is limited to primarily case reports. Feasibility of studies on the subject may be a considerable barrier to further research assessing the use of transplant for treating psoriasis, but there is potential benefit from transplant for psoriasis patients. This subject should receive further exploration to fully understand these benefits.

Introduction

Transplantation is becoming increasingly prevalent. From 2015 to 2019, the number of organ donors and organ transplants performed in the USA each increased by approximately 28%, with new records set every year [1]. In addition to solid organ transplantation, stem cell transplantation (including mesenchymal stem cells (MSC) and hematopoietic stem cell transplantation (HSCT)) has shown promise as a curative modality for several diseases. Worldwide, use of HSCTs has increased by over 7% each year in recent decades [2]. As the number of transplants increases, clinicians are increasingly faced with the challenges of diagnosing and treating skin diseases in solid organ transplant and stem cell recipients.

Psoriasis is an inflammatory skin condition with no known cure. Psoriasis affects about 3% of the US adult population [3, 4]. Despite recent advances, much of the etiology of psoriasis is still unclear; however, known risk factors include genetic, environmental, and behavioral factors, with genetic factors being the largest contributor [5]. The pathogenesis of psoriasis is complex and has yet to be fully described. Plaque psoriasis, the most common variant, involves a feed-forward mechanism of inflammation, primarily including the T-helper cell type 17 pathway [5]. The medical community continues to learn more about the pathogenesis of psoriasis as new treatments are developed.

Since both solid organ transplants and stem cell transplants result in patients who are chimeras to some degree, the evolution of psoriasis in these unique patients has interesting implications for the pathogenesis of the disease. In this review, we synthesize literature on the relationship between psoriasis and solid organ transplant and stem cell transplant to identify considerations dermatologists need to address when treating patients who have undergone these procedures.

Psoriasis in stem cell recipients

Stem cell therapy includes HSCT and MSC. In a standard HSCT regimen, the patient’s native bone marrow, including stem cells, is ablated via aggressive chemotherapy and/or radiation prior to transplantation in a procedure called “myeloablation” or “conditioning.” Cell sources for HSCT are allogeneic (from a donor) or autologous (from the patient). Sources for stem cells include bone marrow, peripheral blood, and umbilical cord blood. The goal is for the transplanted cells to replace the ablated cells. Cases have been reported both of patients experiencing remission and, conversely, of developing psoriasis after HSCT.

In contrast to HSCT, MSC transplants involve isolation and preparation of stem cells which are subsequently injected locally or intravenously without any preceding myeloablation or conditioning. The tissues from which MSCs are harvested include, but are not limited to, human gingival tissue, umbilical cord, and adipose tissue. MSC is most commonly used for regenerative medicine or as therapy for cancer or autoinflammatory diseases. These transplants are often allogeneic, though autologous MSC harvest and transplantation is also possible. Our review of the literature failed to show any cases of psoriasis developing after MSC transplantation, though a growing number of cases describe patients who have cleared their psoriasis after MSC transplantation.

Psoriasis remission following stem cell transplant

From a literature review of sources from PubMed and further review for relevant articles, we identified 29 cases of psoriasis remission after allogeneic stem cell transplant and 17 cases of psoriasis remission following autologous stem cell transplant were identified by the authors; these cases are noted in Table 1. Such cases incite speculation about the mechanisms behind remission, implications about the pathophysiology of psoriasis, and the central role that stem cells play in psoriasis.

Table 1.

Reported cases of psoriasis in remission following stem cell transplant

No	Age/gender	Type of txpa	Indication for txp	Length of psoriasis remission post-txpb	Relapses	Notes on psoriasis severity (as described by the authors) and course	Year reported	References
Allogeneic
1	36/M	BMT	AML	4.5 years	None	Severe psoriasis before txp that remitted after txp	1990	Eedy et al. [44]
2	35/M	BMT	CML	3 years	None	History of moderately severe psoriasis with psoriatic arthropathy that cleared after txp	1990	Jowitt and Yin [45]
3	35/M	BMT	CML	5 years	None	Moderately severe psoriasis with psoriatic arthropathy that remitted after txp	1992	Yin and Jowitt [12]
4	36/M	BMT	Aplastic anemia	3 years	None	Before txp, psoriatic plaques and nail involvement; plaques disappeared and nails improved after txp	1996	Yokota et al. [46]
5	40/M	BMT	AML	2 years	None	Developed palmoplantar pustular psoriasis after receiving three courses of chemotherapy for AML, but this remitted after txp	1997	Kishimoto et al. [47]
6	54/M	BMT	CML	1 year	Relapse after 1 year	Plaques on elbows and inguinal regions as well as nail pitting; psoriatic symptoms remitted three months after txp	1998	Snowden et al. [48]
7	55/F	BMT	CML	2.4 years (died 2.4 years after txp)	None	Psoriatic plaques involved over 2/3 of the patient’s BSA; these started to clear after commencing the conditioning regimen that included busulfan and cyclophosphamide; there was minimal evidence of plaques by the time of txp and these remitted by seven days post-txp	2000	Adkins et al. [49]
8	38/M	BMT	CML	2 years	Reactivation at day +32; resolved by day +78 concurrent with development of GVHD after cyclosporine withdrawal	Before txp, there was “extensive psoriasis on the forehead and most of the skull, neck, chest wall, both hands and arms, legs, genitals, and nails”; by day +21, symptoms of psoriatic polyarthritis had cleared and cutaneous psoriasis was progressively improving	2000	Slavin et al. [13]
9	50/M	PBSCT	Non-Hodgkin’s lymphoma	1.42 years	None	At txp, psoriasis involved nails and 90% of BSA; psoriatic lesions disappeared after four weeks post-txp and nails improved by 90% with some changes in the toenails still present after the 17 months of follow-up	2001	Chakrabarti et al. [6]
10	49/M	BMT	CML	2.5 years	None	Psoriasis for 20 years was treated with topical corticosteroids, but this progressed to injection-site lesions after receiving interferon treatment for CML before txp; psoriasis cleared after txp	2002	Kanamori et al. [50]
11	67/M	RIST	AML	0.58 years	Reactivation at day +42; resolved by day +105 concurrent with development of GVHD after cyclosporine withdrawal	Moderate psoriasis determined using PASI score; lesions cleared after using fludarabine from days −8 to −3 before txp and remained clear at discharge on day +34 post-txp, but psoriasis returned by day +42	2003	Kojima et al. [9]
12	31/M	BMT	AML	17 years	None	Severe psoriasis was treated with razoxane and led to frequent hospitalizations over 20 years; remitted after txp	2004	Windrum et al. [51]
13	36/F	PBSCT	AML	Not specified	None	Severe chronic plaque psoriasis before txp; remitted after txp	2005	He et al. [15]
14	34/F	BMT	AML	0.5 years	None	Severe chronic plaque psoriasis before txp; remitted after txp	2005	He et al. [15]
15	46/M	BMT	AML	2 years	None	Severe chronic plaque psoriasis before txp; remitted by 71 days after txp	2005	He et al. [15]
16	29/M	HSCT (unspecified)	Aplastic anemia	20 years	1 year	“Extensive psoriasis” and severe polyarthritis, though these improved after using high-dose steroids, antithymocyte globulin, and cyclosporine before txp; psoriasis rapidly improved within six months after txp and remained clear for 12 months, with mild symptoms again by five years post-txp	2006	Woods and Mant [10]
17	27/M	BMT	Aplastic anemia	10 years	None	Psoriatic plaques on pretibial regions, knees, elbows and scalp before txp; gradually remitted post-txp	2006	Masszi et al. [7]
18	54/M	BMT	Myelodysplastic syndrome 0.67 years	None	Psoriasis persisted for ten years pre-txp; remitted after txp		2012	Mori et al. [52]
19	56/M	RIST	DLBCL	2 years	None	Psoriasis BSA coverage was 10% but remitted by 15 days post-txp	2013	Kaffenberger et al. [53]
20	35/M	UCMSC	DLBCL	5 years	Reactivation at day +42 HSCT; patient later underwent UCMSC transplant resulting in improvement without reactivation	Two previous autologous HSCTs did not improve psoriasis (described as “numerous erythematous plaques with adherent silvery scales symmetrically distributed throughout the patient’s body”); UCMSC cleared the psoriasis within 12 months	2016	Chen et al. [18]
21	26/F	UCMSC	Psoriasis	4 years	None	Psoriatic plaques with scales pre-txp; after three infusions of UCMSC for three successive weeks and then two infusions of UCMSC three months later, psoriasis remitted	2016	Chen et al. [18]
22	55/F	HSCT (unspecified)	AML	Median follow-up of 5.3 years in the study	None	Moderate psoriasis on elbows and knees as well as psoriatic arthritis pre-txp; these cleared by 37 days post-txp	2019	Ciurea et al. [54]
23	21/M	HSCT (unspecified)	AML	Median follow-up of 5.3 years in the study	None	Mild-to-moderate psoriasis on bilateral elbows and neck pre-txp; cleared by 64 days post-txp	2019	Ciurea et al. [54]
24	59/M	RIST	DLBCL	Median follow-up of 5.3 years in the study	None	Severe psoriasis on scalp, elbows, arms, and knees with psoriatic arthritis pre-txp; these cleared by 60 days post-txp	2019	Ciurea et al. [54]
25	65/M	RIST	AML	Median follow-up of 5.3 years in the study	None	Severe psoriasis including nail involvement and psoriatic arthritis pre-txp; psoriatic lesions cleared by day +41 post-txp, though psoriatic arthritis improved more slowly with pain and swelling resolving by about nine weeks post-txp	2019	Ciurea et al. [54]
26	30/F	RIST	Follicular lymphoma/DLBCL Median follow-up of 5.3 years in the study		None	Moderate psoriasis affecting the nails and skin; these remitted by 30 days post-txp	2019	Ciurea et al. [54]
27	65/M	HSCT (unspecified)	Chronic neutrophilic leukemia Median follow-up of 5.3 years in the study		None	Moderate psoriasis affecting the upper and lower extremities; remitted by 71 days post-txp	2019	Ciurea et al. [54]
28	19/M	MSC	Psoriasis	3 years	None	Severe plaque psoriasis pre-txp; after two successive weekly infusions of MSC, the psoriatic lesions started to clear, and they fully cleared after three additional MSC infusions that were given five weeks later	2020	Wang et al. [21]
Autologous
30	35/M	PBSCT	Burkitt’s lymphoma	1.83 years	Relapse after 1.83 years; more severe	Fifteen-year history of intermittent mild plaque psoriasis, though no active lesions four months pre-txp; psoriasis and possible psoriatic arthritis requiring nonsteroidal anti-inflammatory drugs and intraarticular corticosteroid injections occurred almost two years post-txp	1997	Cooley et al. [8]
31	53/M	BMT	AML	1.17 years	Relapse after 1.17 years	Psoriasis was treated with topicals pre-txp; psoriasis cleared after txp but returned, requiring dithranol and psoralen ultraviolet A therapy for treatment	1997	Cooley et al. [8]
32	40/F	PBSCT	Plasma cell leukemia	0.67 years	Relapse after 0.67 years	Long-term “widespread” psoriasis cleared after the third cycle of chemotherapy pre-txp; psoriasis cleared over six months post-txp but returned on the legs by eight months post-txp	1997	Cooley et al. [8]
33	34/M	PBSCT	Psoriasis, monoclonal gammopathy of undetermined significance	1.33 years	None	Psoriatic arthropathy with some skin lesions pre-txp; within three days after cyclophosphamide treatment, the psoriatic arthritis and skin lesions resolved, though mild polyarthritis returned 16 months post-txp	2004	Mohren et al. [55]
34	50/M	BMT	Non-Hodgkin’s lymphoma	1.75 years	Relapse after 1.75 years	Psoriasis on elbows and scalp pre-txp; cleared after txp, though eventually returned with smaller, less scaly, and thinner lesions	2006	Masszi et al. [7]
35	35/M	PBSCT	Multiple myeloma	1.25 years	None	Psoriatic arthropathy, nail involvement, and skin involvement of 50% of BSA pre-txp; remission after txp	2008	Braiteh et al. [25]
36	9/M	HSCT (unspecified)	Autologous stem cell rescue after chemotherapy for Ewing’s sarcoma	1.25 years	None	Severe guttate psoriasis affecting approximately 100% of BSA pre-txp; psoriasis was almost completely clear by day +20 and was clear 15 months post-txp	2012	Held et al. [56]
37	48/F	HSCT (unspecified)	Multiple myeloma	13 years	Relapse after 13 years	Moderate-to-severe plaque psoriasis pre-txp; remission for 13 years, after which mild flares occurred	2015	Sung and Kimball [57]
38	58/M	MSC	Psoriasis	Did not achieve complete clearance, though relapsed after 2 years	Relapse after 2 years	“Generalized” psoriasis, nail involvement, and arthritis pre-txp; received two MSC infusions with a PASI score of 21.6 on the day of first infusion that declined to 8.9 after 40 days, though psoriasis relapsed after the patient developed pulmonary tuberculosis two years post-txp	2016	De Jesus et al. [26]
39	28/F	MSC	Psoriasis	Did not achieve complete clearance, though relapsed after 0.8 years	Relapse after 0.8 years	PASI of 24 on day of first MSC infusion, 18.3 on day of second infusion, and 9.4 on day of third infusion; 45 days after the third infusion, the PASI score was 9.6 and then declined further to 8.3 on day +231, though a recurrent flare occurred after day +292	2016	De Jesus et al. [26]
40	54/M	PBSCT	Multiple myeloma	3.25 years	None	Severe psoriasis pre-txp; gradually cleared over three months post-txp	2017	Azevedo et al. [58]
41	53/M	HSCT (unspecified)	Hodgkin’s lymphoma	1 year	None	Psoriasis that partly improved on topical steroids before txp; lesions were mostly clear at three months post-txp and then were clear at one year post-txp	2018	Kaloyannidis et al. [59]
42	58/M	HSCT (unspecified)	Immunoglobulin light chain amyloidosis	7 years	None	Psoriasis affecting over 50% of the patient’s BSA pre-txp; gradually cleared after txp	2018	Chen et al. [60]
43	65/M	BMT	Multiple myeloma	2.17 years	None	PASI score of 2.4 before txp and 0.0 after txp	2021	Ugur and Gediz [61]
44	67/F	BMT	Multiple myeloma	1.58 years	None	PASI score of 4.7 before txp and 0.0 after txp	2021	Ugur and Gediz [61]
45	65/F	BMT	Multiple myeloma	1.25 years	None	PASI score of 13.4 before txp and 2.4 after txp, though psoriasis remission occurred 15 months post-txp	2021	Ugur and Gediz [61]
46	55/F	BMT	Multiple myeloma	1.83 years	None	PASI score of 33.3 before txp and 0.0 after txp	2021	Ugur and Gediz [61]

AML acute myeloid leukemia; BMT bone marrow transplant; BSA body surface area; CML chronic myeloid leukemia; DLBCL diffuse large B cell lymphoma; GVHD graft-versus-host disease; HSCT hematopoietic stem cell transplant; MSC mesenchymal stem cell; PASI Psoriasis Area and Severity Index; PBSCT peripheral blood stem cell transplant; RIST reduced-intensity stem cell transplantation; Txp transplant; UCMSC umbilical cord-derived mesenchymal stem cells

^aBased on what was mentioned as the txp by the articles’ authors. More specific categories were used where possible, though not all articles offered specifics on type of stem cell transplant

^bAmount of time between txp and the time of publication unless time between txp and recurrence or end of follow-up was specified in the article

Allogeneic stem cell transplant and psoriasis remission

Psoriasis improvement during HSCT is due at least in part to the profound immunosuppression achieved during conditioning [6] and after transplant as prophylaxis against graft-versus-host disease (GVHD) [7]. The immunosuppressive drugs used in these regimens also suppress the pathogenic cells responsible for causing psoriasis [8]. Encouragingly, the clearance that develops after allogeneic transplant is potentially durable [9], with reported remissions of up to 20 years without further immunosuppression [10], thus suggesting an additional mechanism yet to be discovered. This phenomenon stands in contrast to autologous HSCT, as the autologous cases more commonly result in relapse of psoriasis after initial improvement (as shown in Table 1).

In allogeneic transplant, pre-transplant myeloablation eliminates most of the host’s lymphocytes, including those that cause psoriasis, contributing to initial remission [11]. Any regimen that does not achieve complete myeloablation risks repopulation of the bone marrow with the patient’s own lymphocytes and thus relapse [12]. However, even patients with partial chimerism—with T cells of both donor and host origin—may experience improvement in psoriasis, suggesting that even in the presence of pathogenic lymphocytes, the general immunologic milieu may influence the disease’s progression [6, 9].

One target of donor lymphocytes may be remaining host-derived lymphocytes [13]. Donor lymphocytes in GVHD, particularly CD8+ T cells, play a key role in the recovery and remission of malignancies as well as of inflammatory diseases such as psoriasis [14]. Studies report that patients who experience even mild GVHD also experience remissions of inflammatory conditions, including psoriasis and rheumatoid arthritis, possibly due to a “graft-versus-autoimmunity” effect [6, 8, 11]. Alternatively, disease improvement could be due to the continued, aggressive immunosuppression used to control these patients’ GVHD [7].

While HSCT is not a primary therapy for psoriasis [6], patients may be able to expect improvement in their psoriasis following HSCT performed for another reason. For patients with both severe psoriasis and leukemia, allogeneic HSCT, rather than chemotherapy, may be a treatment of choice [15]. However, even for severe psoriasis patients without leukemia, the risks and financial costs of the transplantation procedure (including pre-transplant myeloablation) outweigh the potential curative benefits, especially given the efficacy and safety of current psoriasis biologic medications.

Mesenchymal stem cell transplant and psoriasis remission

Several reports show that MSCs may have potential as an alternative treatment for psoriasis [16–20]. One of the first observations of this phenomenon was described in 2016 by Chen and colleagues [18]. In this case, a 35-year-old man with lymphoma developed psoriasis prior to an autologous HSCT. The distribution of plaques decreased after the conditioning regimens for HSCT, but new psoriasis lesions appeared within six weeks. The patient was given one dose of allogeneic umbilical cord-derived mesenchymal stem cells (UCMSCs) to support the engraftment. Unexpectedly, his skin lesions (as well as the engraftment) slowly improved with complete remission of his psoriasis by six months [18]. In contrast to HSCT, MSC therapy does not require a cytotoxic conditioning regimen. This makes MSC therapy safer than HSCT. Additionally, MSCs have been used in other autoinflammatory diseases [19]. These findings have led to two subsequent reports of patients receiving allogeneic MSC transplants with the primary indication being to cure psoriasis, both of which are described in Table 1 [21, 22]. In both cases, psoriasis lesions fully resolved with no recurrence. The therapeutic effect of these cells is thought to be a result of their potent anti-inflammatory and immunomodulatory effects as well as their immunoevasive properties [19, 23]. These initial observations suggest that MSCs may be a safe and effective treatment for psoriasis. As such, several phase I–II clinical trials are now in process using allogeneic MSCs as a treatment for psoriasis, a list of which can be found in a review article by Lwin and colleagues [20]. In one phase 1/2a single-arm trial, 8 of 17 patients had at least 40% improvement in PASI scores after six months of UCMSC infusions, and 3 of 17 had more than 90% improvement in PASI scores [24]. Additionally, all responders showed significant increase in Tregs and CD4+ memory T cells, further illustrating the immunomodulatory properties of MSCs in psoriasis [24].

Autologous stem cell transplant and psoriasis remission

In the rare and transient remissions following autologous transplantation, one proposed mechanism is the “resetting of immunologic memory” [25], or “altered immune reconstitution” [8]. In this scenario, pre-transplant conditioning ablates the pathogenic lymphocytes. Following autologous transplantation, de novo naïve lymphocytes repopulate the bone marrow; this new population exhibits the self-tolerance that the original population lacked. Several hypotheses might explain the near-total failure of autologous HSCT to result in durable remissions of autoimmune disease. The patient’s own pathogenic cells may be transplanted along with healthy cells [7]. The patient’s immune milieu may be exposed to similar triggers—endogenous or exogenous—that triggered psoriasis originally [7]. One report posits that post-HSCT treatment with interferon-α provoked a relapse [8]. In addition, autologous “cures” may be primarily due to aggressive immunosuppression and myeloablation [6]. These treatments are transient, and thus, so are the remissions. Even though the initial improvement in psoriasis with autologous HSCT is commonly followed by a relapse, in most cases the relapsed psoriasis displays a milder course compared with the pre-transplant disease [20].

As far as psoriasis clearing after autologous MSC, only one report was found in the literature: Two patients were each given autologous lipoaspirate-derived MSCs in conjunction with other systemic therapies for psoriasis and psoriatic arthritis, such as etanercept and methotrexate. Both patients experienced relapses of psoriasis after MSC therapy, with only one patient experiencing a durable response. The patient whose response was not durable experienced a transient response due to a tuberculosis infection after MSC transplantation. However, the clinical benefit of systemic therapies increased after MSC therapy, implying that autologous MSC transplantation may show utility when used together with other standard psoriasis medications. Interestingly, the patient who demonstrated a durable response to autologous MSC transplantation was found to have a significant decrease in reactive oxygen species levels after transplantation, implying that oxidative stress may be involved, whether directly or indirectly, to observations made after transplantation of autologous MSCs [26].

Psoriasis appearing after HSCT

A more limited body of research reports the development of psoriasis in patients after receiving HSCTs (Table 2). (Of note, we found no cases of new onset psoriasis after MSCs.) Several autoimmune diseases, including autoimmune thyroiditis and autoimmune hemolytic anemia, have been reported after autologous HSCT [27]. In one retrospective study of 347 patients who had received autologous HSCTs for primary autoimmune diseases, 29 developed at least one secondary immune-mediated disease, one being psoriasis [27].

Table 2.

Reported cases of psoriasis occurring following allogeneic or autologous stem cell transplant

No	Age/gender	Type of txpa	Indication for txp	Presence of psoriasis in donor?	Time post-txp that psoriasis developed	Method of psoriasis diagnosis	Notes on psoriasis severity (as described by the authors) and course	Year reported	References
Allogeneic
47	24/F	BMT	Non-Hodgkin’s lymphoma	Yes	175 days	Skin biopsy	No psoriasis pre-txp, but post-txp, developed plaques on the elbows, neck, face, and shoulders and punctuate dimpling occurred on the nail plate	1990	Gardembas-Pain et al. [30]
48	40/M	BMT (syngeneic)	CML	Yes	10 days	Clinical	Patient did not have a history of rash or arthropathy pre-txp, but developed psoriasis on the back, neck, trunk, and legs	1997	Snowden and Heaton [31]
49	43/M	BMT	CML	Yes	1 year	Unreported	Developed psoriatic lesions on the scalp and nails as well as psoriatic arthritis post-Txp	1999	Daikeler et al. [28]
50	12/F	CBT	Acute lymphoblastic leukemia	Unknown	185 days	Skin biopsy	Diagnosed with erythrodermic psoriasis five days after stopping immunosuppressive treatment post-txp	2007	Hubiche et al. [29]
51	24/F	PBSCT	Non-Hodgkin’s lymphoma (diffuse small cell)	No	10 years	Skin biopsy	Psoriatic plaques developed on the extremities, trunk, and head post-txp	2012	Mabuchi et al. [62]
52	9/M	PBSCT	AML	No	45 days	Skin biopsy	Generalized pustular psoriasis was eventually diagnosed, though two biopsies were needed to help distinguish between psoriasis and graft-versus-host disease	2015	George et al. [63]
53	35/M	BMT	AML	Yes	1 year	Skin biopsy and clinical	Psoriatic lesions developed on back, chest, and all four limbs after ceasing immunosuppression post-txp	2015	Li et al. [64]
54	14 pediatric patients in a cross-sectional study of outcomes post-txp	HSCT (unspecified)	Not reported	Not reported	Not reported	Cutaneous observation	Eleven of the patients were diagnosed with sebopsoriasis; five had psoriasis affecting the face, and one had psoriasis on other body areas	2018	Huang et al. [65]
55	13/F	CBT	Precursor B cell lymphoblastic leukemia	Unknown	19 months	Skin biopsy	Developed psoriatic arthritis and psoriatic lesions on the head, trunk, and extremities	2021	Terui et al. [66]
56	9/M	CBT	AML	Unknown	7 years	Clinical	Psoriasis on the head, trunk, and extremity	2021	Terui et al. [66]
Autologous
57	33/M	HSCT (unspecified)	Non-Hodgkin’s lymphoma (T cell origin)	No	12 weeks	Skin biopsy and clinical	Developed psoriasis on the extremities and axillae 12 weeks post-txp with arthropathy developing later as well	2006	Wahie et al. [32]
58	Patient from a retrospective study	HSCT (unspecified)	Rheumatoid arthritis	No	Not reported	Not reported	347 autologous HSCT recipients; one patient developed psoriasis, though there was no mention of severity	2011	Daikeler et al. [27]

AML acute myeloid leukemia; BMT bone marrow transplant; CBT cord blood transplant; CML chronic myeloid leukemia; HSCT hematopoietic stem cell transplant; NBUVB narrowband ultraviolet B; NIS Nationwide Inpatient Sample; PBSCT peripheral blood stem cell transplant; Txp transplant

^aBased on what was mentioned as the txp by the articles’ authors. More specific categories were used where possible, though not all articles offered specifics on type of stem cell transplant

Several proposed mechanisms may explain the development of psoriasis following allogeneic HSCT. Among the six reported cases in Table 2 in which the donor’s status is known, in four (67%), the donor had psoriasis—a fact that underscores the importance of hematopoietic cells in the pathogenesis of psoriasis. This observation suggests the transfer of autoreactive T cells from donor to recipient as a probable cause [28]. Similarly, the transfer of autoreactive stem cells, rather than mature lymphocytes, may be responsible [29]. Of the four instances of donors with psoriasis, three of the recipients had family histories of psoriasis and received donated cells from siblings with psoriasis [28, 30, 31], so a genetic predisposition may be partially responsible for psoriasis in these cases as well.

The myeloablative regimens preceding HSCT necessitate a reconstitution of the patient’s immune system. Thymic function decreases in adulthood, so the negative selection of new T cells in adults—including most patients discussed in this review—may be less stringent, allowing the maturation of autoreactive T cells. The literature contains one case report and an observational study reporting the development of psoriasis after autologous HSCT (Table 2). From these reports, it seems possible that chemotherapy and conditioning may initiate autoimmune or autoinflammatory disease by damaging keratinocytes and exposing autoantigens or by altering the thymic environment and thus influencing positive and negative selection [27, 32, 33]. Alternatively, these procedures could directly and differentially affect stem cells or regulatory T cells [32].

Clinicians should also be aware that GVHD can mimic psoriasis and should be considered in patients who develop psoriatic lesions after transplantation [34–36]. Psoriasiform manifestations, which may develop the histology and presentation of both psoriasis and GVHD, can occur even if the host and donor do not have a history of psoriasis or other skin disease [34–36]. Special consideration is needed for treating this reaction; as described in two case reports, topical steroids, topical vitamin D analogs, and systemic agents such as cyclosporine and methotrexate do not appear to be effective for psoriasiform manifestations related to GVHD [34, 35]. Alternative treatment courses include topical psoralen ultraviolet A therapy.

Psoriasis in solid organ transplant recipients

Reports of patients with psoriasis and solid organ transplants are commonly limited to patients who had psoriasis both prior to and following their transplantation, with fewer cases of relapse-free psoriasis remission post-transplant [37, 38] and de novo psoriasis following transplantation [38–41]. This phenomenon is not unexpected given the low transfer of lymphocytes from donor to recipient during solid organ transplantation. In these de novo cases, it is unclear whether the new psoriasis can be attributed to the transplant procedure itself, the immunosuppressive drugs taken after the transplant, psychological stress that may act as a trigger, or if the co-occurrence is purely coincidental. For example, a kidney transplant patient developed de novo psoriasis in close association with their transplant but also in association with a change in their immunosuppressive maintenance therapy from tacrolimus to belatacept (due to tacrolimus toxicity) [41]. This patient’s psoriasis improved rapidly after removal of the belatacept, which suggests a potential causal association between the psoriasis and the immunosuppressive medication rather than with the organ transplant itself [41]. One hypothesis for this phenomenon suggests that belatacept (a CTLA4-IG fusion protein) specifically could dysregulate immunity by inhibiting regulatory T cells via its antagonist effects on CD80/86, the ligand for CD28 (essential for Treg maintenance and generation) and CTLA-4 (required for Treg functioning) [42].

Table 3 describes 30 cases of psoriasis occurring after solid organ transplant. The National Psoriasis Foundation recently provided recommendations for selecting appropriate psoriasis treatment in transplant patients [43].

Table 3.

Reported cases of psoriasis occurring after solid organ transplant

No	Age/gender	Type of txp	Indication for txp	Notes on psoriasis severity (as described by the authors) and course	Year reported	Reference
59	24/M	Kidney	Minimal change glomerulo-nephropathy	Flare of pre-existing generalized pustular psoriasis twice after withdrawal of steroids to treat graft rejection; long-term remission achieved with methotrexate	1988	Coulson et al. [67]
60	5 adult patients	Kidney	Unspecified	Five patients suffered from psoriasis (no explanation of severity) both before and after kidney transplant	2005	Formicone et al. [68]
61	31/F	Kidney	Chronic nephropathy	Erythematous and pustular lesions developed 31 months post-txp and were eventually diagnosed as pustular psoriasis via skin biopsy	2007	Kaaroud et al. [69]
62	63/M	Liver	Cryptogenic cirrhosis	Severe exacerbation of long-standing psoriasis that covered 50% of BSA at presentation five years after txp	2007	Hoover [70]
63	49/M	Liver	Hepatocellular carcinoma	Patient had a history of psoriasis and psoriatic arthritis and developed a severe exacerbation of psoriasis covering 30% of BSA as well as worse psoriatic arthritis one year after txp	2008	Collazo, Gonzalez, and Torres [71]
64	42/M	Combined kidney and pancreas and then pancreas retransplantation	Goodpasture syndrome and type 1 diabetes mellitus; later retransplantation of pancreas after chronic dysfunction of original allograft	Severe exacerbation of refractory plaque psoriasis one year after pancreas retransplantation	2012	Brokalaki et al. [72]
65	50/M	Kidney	Focal segmental glomerulosclerosis	Exacerbation of psoriasis post-txp; psoriasis covered 20.2% of BSA, with a PASI score of 15.5	2013	Mansouri et al. [73]
66	55/F	Liver	Primary biliary cirrhosis	Eight-year history of psoriasis pre-txp; remission occurred within three weeks post-txp, but a relapse of psoriasis, attributed to an immune-related process dependent on immunosuppression changes, occurred a year after txp with a PASI score of 11.2	2014	Foroncewicz et al. [38]
67	52/F	Liver	Primary biliary cirrhosis	De novo psoriasis with lesions on the knees and elbows three years after txp	2014	Foroncewicz et al. [38]
68	49/F	Liver	Autoimmune hepatitis	Twenty-year history of psoriasis pre-txp; psoriasis initially cleared but relapsed after six months post-txp with a PASI score of 26.6	2014	Foroncewicz et al. [38]
69	2/M	Liver	Progressive liver disease	De novo psoriasis in a child two years after txp	2015	Sheu et al. [40]
70	55/M	Kidney	Chronic kidney disease	Thirty-seven-year history of severe and refractory psoriasis before txp, believed to have gone into remission immediately prior to txp; psoriasis relapsed on the trunk and limbs two months after txp	2015	Wei and Lai [74]
71	52/M	Liver	Not reported	Plaque psoriasis began five years before txp and continued for five years post-txp	2015	Madankumar et al. [75]
72	49/M	Kidney	Not reported	Whether the patient had psoriasis before txp was not reported; the patient had pustular psoriasis post-txp	2016	Garrouste et al. [76]
73	56/M	Liver	Alcoholic cirrhosis	Psoriasis for possibly one year before txp; severe psoriasis with a PASI score of 26.2 three years post-txp, and etanercept treatment led to a reduced PASI score of 3.5	2016	De Simone et al. [77]
74	63/M	Kidney	Chronic kidney disease	Psoriasis prior to txp; psoriasis was clear by two months post-txp, though psoriatic lesions returned two years after txp	2016	Cicora and Roberti [78]
75	53/M	Kidney	End-stage renal failure	Psoriasis prior to txp; psoriasis present at 15 months post-txp	2016	Cicora and Roberti [78]
76	47/M	Kidney three times	End-stage renal disease	First symptoms of psoriasis appeared between first and second txp and progressed, with a PASI score of 7.8 and flares common after the second txp; the patient developed spondylitic psoriatic arthritis after the third txp, but treatment with belatacept improved psoriasis and psoriatic arthritis symptoms, with an improved PASI score of 2.1 and less frequent and less severe psoriasis symptoms over the following four years	2017	Meneghini et al. [39]
77	51/M	Liver	Not reported	Psoriasis with PASI score of 46 and relapse of psoriasis about two years after txp; remission achieved with sirolimus	2017	Zhou et al. [37]
78	55/F	Liver	Not reported	Psoriasis with PASI score of 41 and relapse of psoriasis about two years after txp; remission achieved with sirolimus	2017	Zhou et al. [37]
79	39/M	Kidney	Chronic kidney disease	Mild psoriasis since childhood, but psoriasis was aggravated post-txp with lesions eventually expanding to the entire body; cyclosporine, corticosteroids, and methotrexate were unsuccessful, and the patient died on day +57 from multiorgan failure	2018	Dedemadi et al. [79]
80	42/M	Kidney	End-stage renal disease	De novo psoriasis eight months after txp; psoriasis cleared after stopping belatacept and re-introducing mycophenolic acid	2018	Ville and Cantarovich [41]
81	54/M	Liver	Hepatitis C cirrhosis	Patient with history of psoriasis experienced a psoriasis flare with a PASI score of 15 at 10 years after txp	2019	Lora et al. [80]
82	67/M	Kidney	Chronic tubulointerstitial nephritis	Patient with psoriasis before txp had severe psoriasis (PASI 15) after txp; his psoriasis cleared with etanercept	2020	García-Zamora et al. [81]
83	35/M	Kidney	Likely chronic renal failure	Treated for severe flare of long-standing plaque psoriasis that started to clear on ixekizumab before txp; no further mention of severity post-txp, but ixekizumab use continued after txp	2020	Di Altobrando et al. [82]
84	50/M	Liver	Hepatitis C cirrhosis	Fifteen-year history of moderate-to-severe plaque psoriasis and psoriatic arthritis; 40% of BSA was affected post-txp	2021	Singh et al. [83]

BSA body surface area; PASI Psoriasis Area and Severity Index; Txp transplant

Limitations of current literature

Much of the literature found for this paper was type D, meaning case reports or small case series. Evidence from larger studies could formally assess the effects of transplantation on psoriasis as well as the incidence of psoriasis remission and new-onset psoriasis in this population. However, significant challenges exist regarding this type of research. Though the number of solid organ transplants and stem cell transplants is increasing, this population is still relatively small [1, 2]. Further, patients are susceptible to other complications due to the nature of existing conditions and the medications and procedures they must undergo for transplantation.

Conclusions

As the field of transplant medicine expands and transplant needs continue to grow in number, dermatologists will increasingly face the challenge of treating and evaluating patients with both psoriasis and a history of transplantation. The cases presented in this review emphasize several observations. First, the clearance of psoriasis that develops after allogeneic transplant is potentially durable, and as such, it is reasonable to consider allogeneic HSCT as a treatment for patients with both severe psoriasis and hematologic malignancies. Second, a growing number of patients experience durable remission of their psoriasis after MSC transplantation. Due to its relative safety and growing evidence of efficacy, MSC transplantation shows potential as a treatment for psoriasis, though more data are needed. Finally, the relationship between psoriasis and transplantation procedures provides clues about the pathogenesis of psoriasis. The cases presented in this review suggest that immunologic self-tolerance, hematopoietic stem cells, immunomodulation, and viability of host lymphocytes all appear to play a role.

Abbreviations

AML

Acute myeloid leukemia

BMT

Bone marrow transplant

BSA

Body surface area

CBT

Cord blood transplant

CML

Chronic myeloid leukemia

DLBCL

Diffuse large B cell lymphoma

GVHD

Graft-versus-host disease

HSCT

Hematopoietic stem cell transplant

MGUS

Monoclonal gammopathy of undetermined significance

MSC

Mesenchymal stem cells

NBUVB

Narrowband ultraviolet B

NIS

Nationwide Inpatient Sample

PASI

Psoriasis Area and Severity Index

PBSCT

Peripheral blood stem cell transplant

RIST

Reduced-intensity stem cell transplantation

Txp

Transplant

UCMSC

Umbilical cord-derived mesenchymal stem cells

Availability of data and material

Not applicable.