CED
Clinical dermatology • Concise report
Clinical and Experimental Dermatology
Generalized pustular psoriasis following allogeneic stem cell transplantation L. George,1 V. Mathews,2 B. George,2 M. Thomas3 and S. A. Pulimood1 Departments of 1Dermatology, 2Haematology and 3Pathology, Christian Medical College, Vellore, Tamil Nadu, India doi:10.1111/ced.12508
Summary
Development of psoriasis following allogeneic stem cell transplantation (SCT) is rare, and has been described once previously, following SCT from a sibling donor with psoriasis. This condition should be differentiated from psoriasiform graft-versus-host disease (GvHD) by histopathology. We describe a 9-year-old boy who developed generalized pustular psoriasis 2 months after allogeneic SCT from an HLA-identical sibling donor with no history of psoriasis. Diagnosis was confirmed by clinical features and multiple skin biopsies, which helped to exclude GvHD. The skin lesions responded well to treatment with acitretin. Psoriasis should be considered in the differential diagnosis of skin rash following SCT.
Psoriasis following allogeneic stem cell transplantation (SCT) is rare, and has been described only once previously, following a sibling transplant from a donor with psoriasis,1 although psoriasiform eruption as part of graft-versus host disease (GvHD) occurring after SCT has been reported.2,3 We report a boy who developed generalized pustular psoriasis (GPP) 2 months after allogeneic SCT from a sibling donor.
Report A 9-year-old boy with relapsed acute myeloid leukaemia received an allogeneic SCT from his human leucocyte antigen (HLA)-identical sister (HLA haplotypes A3, A68, B18, B62, DR13, DR15). He was conditioned with intravenous fludarabine and busulfan from the fifth to the second day before SCT, using peripheral blood stem cells as the graft source. GvHD prophylaxis consisted of tacrolimus and short pulses of methotrexate. Post-SCT, the patient received penicillin and aciclovir prophylaxis from day 20, and twice-weekly cotrimoxazole, which he Correspondence: Dr Leni George, Department of Dermatology, Venereology and Leprosy, Christian Medical College, Vellore, Tamil Nadu, 632004, India E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest Accepted for publication 7 June 2014
ª 2014 British Association of Dermatologists
received on days 21, 22, 28 and 29 post-SCT. On day 30 post-SCT, the patient developed an erythematous maculopapular skin rash. Histological examination of a skin biopsy revealed acute GvHD grade 2. The rash slowly resolved after treatment with oral prednisolone (0.5 mg/kg/day), mycophenolate mofetil 250 mg twice daily and topical mometasone. On day 45 post-SCT, the patient developed high-grade fever, along with erythema and crops of sterile pustules on his face, trunk and extremities (Fig. 1a). Empirical broad-spectrum antibiotics (teicoplanin on days 47–49 and vancomycin and imipenem on days 49–57) were initiated. Intravenous amphotericin B was also administered on days 49–77 for presumed fungal infection. There was no neutrophilia or eosinophilia at the onset of rash (total white cell count 6.3 9 109/L; normal range 4–11 9 109/L; N64, L20, E4, M12). Possibilities considered included drug-induced rash, psoriasiform GvHD, acute generalized exanthematous pustulosis (AGEP) and GPP. Histological examination of a skin biopsy revealed hyperkeratosis with subcorneal neutrophil-rich bulla, acanthosis, spongiosis and focal basal cell vacuolation, with lymphocytic and neutrophilic exocytosis. The dermis showed oedema, telangiectasia, and a mild perivascular inflammatory infiltrate of lymphocytes, histiocytes, neutrophils and scanty eosinophils. These features were suggestive of AGEP/pustular psoriasis, but resolving GvHD could not be excluded.
Clinical and Experimental Dermatology
1
Psoriasis after transplant L. George et al.
(a)
(b)
(c)
Figure 1 (a) Crops of sterile pustules on erythematous skin; (b,c):
pustules with desquamation.
The patient continued to develop recurrent crops of pustules with erythema and desquamation during the subsequent weeks (Fig. 1b,c). A repeat skin biopsy revealed subcorneal pustules, consistent with psoriasis, with no evidence of GvHD. There was also psoriasiform hyperplasia with parakeratosis, suprapapillary thinning and dilatation of dermal blood vessels, with mild perivascular inflammatory infiltrate consisting predominantly of lymphocytes, as well as scanty eosinophils and a few neutrophils. No interface changes, necrotic keratinocytes, satellite cell necrosis or tissue eosinophilia were seen, thus excluding GvHD and drug reactions (Fig 2). The clinical presentation of recurrent waves of pustulation along with the histological features were more suggestive of pustular psoriasis. No precipitating factors could be identified, and there was no personal or family history of psoriasis. HLA CW6 was negative in both donor and patient. The patient was started on methotrexate 10 mg once a week with narrowband ultraviolet B (NB-UVB) phototherapy. Acitretin 0.4 mg/kg was added on day 119, owing to inadequate response at 3 weeks, and NB-UVB was discontinued. With this, there was rapid improvement in the skin lesions. On day 168 post-SCT, the patient developed arthropathy involving both ankle joints, along with nail pitting and distal onycholysis of all fingernails. There were a few erythematous scaly lesions around his ankles, and a repeat biopsy showed features of psoriasis with no evidence of GvHD. Although the patient’s skin
2
Clinical and Experimental Dermatology
Figure 2 Subcorneal pustule with spongiform areas in the
superficial epidermis (haematoxylin and eosin, original magnification 9 200).
lesions remained in partial remission, he had a relapse of leukaemia 9 months after SCT and died. GPP is an uncommon variant of psoriasis, in which an acute eruption of sterile pustules occurs after steroid withdrawal or other extraneous factors. Although a clinical diagnosis of AGEP was initially considered for our patient because he was on multiple antibiotics, the prolonged course of the illness with the characteristic clinical and histopathological features favoured the diagnosis of GPP. Psoriasiform GvHD was also excluded by subsequent biopsies. Our patient fulfilled the diagnostic criteria for GPP suggested by Umezawa et al.,4 including (i) multiple sterile pustules on erythematous skin, (ii) systemic symptoms of fever and malaise, (iii) presence of histopathologically confirmed spongiform pustules, and (iv) recurrence of clinical and histological findings. Development of psoriasis following syngeneic bone marrow transplantation from a donor with psoriasis was previously quoted as evidence for the passive transfer of causative autoimmune T cells.5 Development of other autoimmune diseases such as systemic lupus erythematosus, ulcerative colitis and paraneoplastic pemphigus following autologous SCT has been
ª 2014 British Association of Dermatologists
Psoriasis after transplant L. George et al.
described previously.6,7 The first case of psoriasis following autologous transplantation was reported by Wahie et al.,8 with no adoptive transfer of autoimmunity, and was believed to occur as a result of myeloablative chemotherapy. Psoriasis has also been reported following cord blood SCT.9 GPP following SCT has not been previously reported. There are several reasons why our patient might have developed psoriasis. High-dose chemotherapy for conditioning may have initiated an autoimmune process by damaging the keratinocytes, and exposing or modifying the autoantigens, thus predisposing to an immune process. Immune imbalance could also result from differences in regulatory T cells, which are implicated in autoimmunity. Immune reconstitution after SCT occurs initially by adoptive transfer of memory cells in the graft, then proliferation of donor T-cell clones occurs, which could result in GvHD or psoriasis. Transfer of abnormal T cells from the donor, as well as other factors, including other immune cells (such as host lymphocytes and keratinocytes), and other stimuli (such as infections, physical and psychological stress during SCT and environmental factors) might also induce psoriasis. In conclusion, psoriasis should be considered in the differential diagnosis of skin lesions after allogeneic SCT. Skin biopsy can be used to differentiate psoriasis from GvHD. It is noteworthy that SCT-linked immunosuppression did not prevent the onset of this disease in our patient, and it responded only to acitretin.
Learning points This is the first case of GPP to be reported after
References 1 Gardembas-Pain M, Ifrah N, Foussard C et al. Psoriasis after allogeneic bone marrow transplantation. Arch Dermatol 1990; 126: 1523. 2 Kawakami Y, Oyama N, Nakamura K et al. Psoriasiform eruption associated with graft-versus-host disease. Acta Derm Venereol 2007; 87: 436–8. 3 Sirinoglu Demiriz I, Tekgunduz E, Tetik A et al. Steroid refractory psoriasiform cutaneous graft versus host disease successfully treated by extracorporeal photopheresis: a case report. Transfus Apher Sci 2013; 48: 109–11. 4 Umezawa Y, Ozawa A, Kawasima T et al. Therapeutic guidelines for the treatment of generalized pustular psoriasis (GPP) based on a proposed classification of disease severity. Arch Dermatol Res 2003; 295 (Suppl.): S43–54. 5 Snowden JA, Heaton DC. Development of psoriasis after syngeneic bone marrow transplant from psoriatic donor: further evidence for adoptive autoimmunity. Br J Dermatol 1997; 137: 130–2. 6 Steinbach WJ, Sandborg CI. Development of systemic lupus erythematosus following autologous bone marrow transplant for acute lymphocytic leukaemia. J Rheumatol 2001; 28: 1467–8. 7 Koike K, Kohda K, Kuga T et al. Ulcerative colitis after autologous peripheral blood stem cell transplantation for non-Hodgkin’s lymphoma. Bone Marrow Transplant 2001; 28: 619–21. 8 Wahie S, Alexandroff A, Reynolds NJ et al. Psoriasis occurring after myeloablative therapy and autologous stem cell transplantation. Br J Dermatol 2006; 154: 194–5. 9 Hubiche T, Leaute-Labreze C, Lepreux S et al. Psoriasis after cord blood stem cell transplantation. Br J Dermatol 2007; 156: 386–8.
allogeneic haematopoietic SCT. Psoriasis should be considered in the differential
diagnosis of papulosquamous skin lesions after SCT. Biopsy distinguishes SCT-associated psoriasis
from psoriasiform GvHD. The donor should be screened for a personal
and family history of psoriasis. Transfer of abnormal donor T cells and other
immune cells during transplant may play a role in acquiring psoriasis. In our case, retinoids in addition to SCT-linked immunosuppression were required to control the GPP.
ª 2014 British Association of Dermatologists
Clinical and Experimental Dermatology
3
Clinical dermatology • Concise report
Clinical and Experimental Dermatology
Generalized pustular psoriasis following allogeneic stem cell transplantation L. George,1 V. Mathews,2 B. George,2 M. Thomas3 and S. A. Pulimood1 Departments of 1Dermatology, 2Haematology and 3Pathology, Christian Medical College, Vellore, Tamil Nadu, India doi:10.1111/ced.12508
Summary
Development of psoriasis following allogeneic stem cell transplantation (SCT) is rare, and has been described once previously, following SCT from a sibling donor with psoriasis. This condition should be differentiated from psoriasiform graft-versus-host disease (GvHD) by histopathology. We describe a 9-year-old boy who developed generalized pustular psoriasis 2 months after allogeneic SCT from an HLA-identical sibling donor with no history of psoriasis. Diagnosis was confirmed by clinical features and multiple skin biopsies, which helped to exclude GvHD. The skin lesions responded well to treatment with acitretin. Psoriasis should be considered in the differential diagnosis of skin rash following SCT.
Psoriasis following allogeneic stem cell transplantation (SCT) is rare, and has been described only once previously, following a sibling transplant from a donor with psoriasis,1 although psoriasiform eruption as part of graft-versus host disease (GvHD) occurring after SCT has been reported.2,3 We report a boy who developed generalized pustular psoriasis (GPP) 2 months after allogeneic SCT from a sibling donor.
Report A 9-year-old boy with relapsed acute myeloid leukaemia received an allogeneic SCT from his human leucocyte antigen (HLA)-identical sister (HLA haplotypes A3, A68, B18, B62, DR13, DR15). He was conditioned with intravenous fludarabine and busulfan from the fifth to the second day before SCT, using peripheral blood stem cells as the graft source. GvHD prophylaxis consisted of tacrolimus and short pulses of methotrexate. Post-SCT, the patient received penicillin and aciclovir prophylaxis from day 20, and twice-weekly cotrimoxazole, which he Correspondence: Dr Leni George, Department of Dermatology, Venereology and Leprosy, Christian Medical College, Vellore, Tamil Nadu, 632004, India E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest Accepted for publication 7 June 2014
ª 2014 British Association of Dermatologists
received on days 21, 22, 28 and 29 post-SCT. On day 30 post-SCT, the patient developed an erythematous maculopapular skin rash. Histological examination of a skin biopsy revealed acute GvHD grade 2. The rash slowly resolved after treatment with oral prednisolone (0.5 mg/kg/day), mycophenolate mofetil 250 mg twice daily and topical mometasone. On day 45 post-SCT, the patient developed high-grade fever, along with erythema and crops of sterile pustules on his face, trunk and extremities (Fig. 1a). Empirical broad-spectrum antibiotics (teicoplanin on days 47–49 and vancomycin and imipenem on days 49–57) were initiated. Intravenous amphotericin B was also administered on days 49–77 for presumed fungal infection. There was no neutrophilia or eosinophilia at the onset of rash (total white cell count 6.3 9 109/L; normal range 4–11 9 109/L; N64, L20, E4, M12). Possibilities considered included drug-induced rash, psoriasiform GvHD, acute generalized exanthematous pustulosis (AGEP) and GPP. Histological examination of a skin biopsy revealed hyperkeratosis with subcorneal neutrophil-rich bulla, acanthosis, spongiosis and focal basal cell vacuolation, with lymphocytic and neutrophilic exocytosis. The dermis showed oedema, telangiectasia, and a mild perivascular inflammatory infiltrate of lymphocytes, histiocytes, neutrophils and scanty eosinophils. These features were suggestive of AGEP/pustular psoriasis, but resolving GvHD could not be excluded.
Clinical and Experimental Dermatology
1
Psoriasis after transplant L. George et al.
(a)
(b)
(c)
Figure 1 (a) Crops of sterile pustules on erythematous skin; (b,c):
pustules with desquamation.
The patient continued to develop recurrent crops of pustules with erythema and desquamation during the subsequent weeks (Fig. 1b,c). A repeat skin biopsy revealed subcorneal pustules, consistent with psoriasis, with no evidence of GvHD. There was also psoriasiform hyperplasia with parakeratosis, suprapapillary thinning and dilatation of dermal blood vessels, with mild perivascular inflammatory infiltrate consisting predominantly of lymphocytes, as well as scanty eosinophils and a few neutrophils. No interface changes, necrotic keratinocytes, satellite cell necrosis or tissue eosinophilia were seen, thus excluding GvHD and drug reactions (Fig 2). The clinical presentation of recurrent waves of pustulation along with the histological features were more suggestive of pustular psoriasis. No precipitating factors could be identified, and there was no personal or family history of psoriasis. HLA CW6 was negative in both donor and patient. The patient was started on methotrexate 10 mg once a week with narrowband ultraviolet B (NB-UVB) phototherapy. Acitretin 0.4 mg/kg was added on day 119, owing to inadequate response at 3 weeks, and NB-UVB was discontinued. With this, there was rapid improvement in the skin lesions. On day 168 post-SCT, the patient developed arthropathy involving both ankle joints, along with nail pitting and distal onycholysis of all fingernails. There were a few erythematous scaly lesions around his ankles, and a repeat biopsy showed features of psoriasis with no evidence of GvHD. Although the patient’s skin
2
Clinical and Experimental Dermatology
Figure 2 Subcorneal pustule with spongiform areas in the
superficial epidermis (haematoxylin and eosin, original magnification 9 200).
lesions remained in partial remission, he had a relapse of leukaemia 9 months after SCT and died. GPP is an uncommon variant of psoriasis, in which an acute eruption of sterile pustules occurs after steroid withdrawal or other extraneous factors. Although a clinical diagnosis of AGEP was initially considered for our patient because he was on multiple antibiotics, the prolonged course of the illness with the characteristic clinical and histopathological features favoured the diagnosis of GPP. Psoriasiform GvHD was also excluded by subsequent biopsies. Our patient fulfilled the diagnostic criteria for GPP suggested by Umezawa et al.,4 including (i) multiple sterile pustules on erythematous skin, (ii) systemic symptoms of fever and malaise, (iii) presence of histopathologically confirmed spongiform pustules, and (iv) recurrence of clinical and histological findings. Development of psoriasis following syngeneic bone marrow transplantation from a donor with psoriasis was previously quoted as evidence for the passive transfer of causative autoimmune T cells.5 Development of other autoimmune diseases such as systemic lupus erythematosus, ulcerative colitis and paraneoplastic pemphigus following autologous SCT has been
ª 2014 British Association of Dermatologists
Psoriasis after transplant L. George et al.
described previously.6,7 The first case of psoriasis following autologous transplantation was reported by Wahie et al.,8 with no adoptive transfer of autoimmunity, and was believed to occur as a result of myeloablative chemotherapy. Psoriasis has also been reported following cord blood SCT.9 GPP following SCT has not been previously reported. There are several reasons why our patient might have developed psoriasis. High-dose chemotherapy for conditioning may have initiated an autoimmune process by damaging the keratinocytes, and exposing or modifying the autoantigens, thus predisposing to an immune process. Immune imbalance could also result from differences in regulatory T cells, which are implicated in autoimmunity. Immune reconstitution after SCT occurs initially by adoptive transfer of memory cells in the graft, then proliferation of donor T-cell clones occurs, which could result in GvHD or psoriasis. Transfer of abnormal T cells from the donor, as well as other factors, including other immune cells (such as host lymphocytes and keratinocytes), and other stimuli (such as infections, physical and psychological stress during SCT and environmental factors) might also induce psoriasis. In conclusion, psoriasis should be considered in the differential diagnosis of skin lesions after allogeneic SCT. Skin biopsy can be used to differentiate psoriasis from GvHD. It is noteworthy that SCT-linked immunosuppression did not prevent the onset of this disease in our patient, and it responded only to acitretin.
Learning points This is the first case of GPP to be reported after
References 1 Gardembas-Pain M, Ifrah N, Foussard C et al. Psoriasis after allogeneic bone marrow transplantation. Arch Dermatol 1990; 126: 1523. 2 Kawakami Y, Oyama N, Nakamura K et al. Psoriasiform eruption associated with graft-versus-host disease. Acta Derm Venereol 2007; 87: 436–8. 3 Sirinoglu Demiriz I, Tekgunduz E, Tetik A et al. Steroid refractory psoriasiform cutaneous graft versus host disease successfully treated by extracorporeal photopheresis: a case report. Transfus Apher Sci 2013; 48: 109–11. 4 Umezawa Y, Ozawa A, Kawasima T et al. Therapeutic guidelines for the treatment of generalized pustular psoriasis (GPP) based on a proposed classification of disease severity. Arch Dermatol Res 2003; 295 (Suppl.): S43–54. 5 Snowden JA, Heaton DC. Development of psoriasis after syngeneic bone marrow transplant from psoriatic donor: further evidence for adoptive autoimmunity. Br J Dermatol 1997; 137: 130–2. 6 Steinbach WJ, Sandborg CI. Development of systemic lupus erythematosus following autologous bone marrow transplant for acute lymphocytic leukaemia. J Rheumatol 2001; 28: 1467–8. 7 Koike K, Kohda K, Kuga T et al. Ulcerative colitis after autologous peripheral blood stem cell transplantation for non-Hodgkin’s lymphoma. Bone Marrow Transplant 2001; 28: 619–21. 8 Wahie S, Alexandroff A, Reynolds NJ et al. Psoriasis occurring after myeloablative therapy and autologous stem cell transplantation. Br J Dermatol 2006; 154: 194–5. 9 Hubiche T, Leaute-Labreze C, Lepreux S et al. Psoriasis after cord blood stem cell transplantation. Br J Dermatol 2007; 156: 386–8.
allogeneic haematopoietic SCT. Psoriasis should be considered in the differential
diagnosis of papulosquamous skin lesions after SCT. Biopsy distinguishes SCT-associated psoriasis
from psoriasiform GvHD. The donor should be screened for a personal
and family history of psoriasis. Transfer of abnormal donor T cells and other
immune cells during transplant may play a role in acquiring psoriasis. In our case, retinoids in addition to SCT-linked immunosuppression were required to control the GPP.
ª 2014 British Association of Dermatologists
Clinical and Experimental Dermatology
3
