Stage IV cutaneous acute graft-versus-host disease. Clinical and histological study of 15 cases

Goiriz, Rebeca; Peñas, P.F.; Pérez‐Gala, S.; Delgado‐Jiménez, Yolanda; Aragüés, Maximiliano; García‐Diez, Amaro; Fraga, Javier; Figuera, Á; Fernández‐Herrera, Jesús

doi:10.1111/j.1468-3083.2009.03326.x

Cited by 13 publications

(11 citation statements)

References 28 publications

(44 reference statements)

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“…More severe cases will require systemic immunosuppressive treatment 6 . Around 2% of cases 20 develop vesicles, epidermal necrosis with positive Nikoslky sign, and generalized erythroderma, resembling toxic epidermal necrolysis (stage IV disease) 21 …”

Section: Acute Graft‐versus‐host Diseasementioning

confidence: 99%

Many faces of graft‐versus‐host disease

Peñas

Zaman

2010

Aust J Dermatology

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Allogeneic haematopoietic stem cell transplantation is increasingly used in the treatment of malignant and non-malignant disorders. Despite ongoing advances in the field, morbidity and mortality related to graft-versus-host disease remains a major barrier to its application. Graft-versus-host disease is a difficult-to-diagnose disease. Dermatologists are involved due to its diverse cutaneous expression. In order to appropriately diagnose, classify and treat this complex disease, knowledge of its expanding cutaneous expression is required. This review provides a synopsis of the clinical manifestations of acute, lichenoid and sclerodermatous phases of graft-versus-host disease with a look at the current evidence surrounding its differential diagnosis.

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Section: Acute Graft‐versus‐host Diseasementioning

confidence: 99%

Many faces of graft‐versus‐host disease

Peñas

Zaman

2010

Aust J Dermatology

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“…Departments of Dermatology, 1 In our case, bullous-type chronic cutaneous GVHD with subepidermal blister formation should be considered as a differential diagnosis. However, our case showed linear IgG deposits in the BMZ and circulating anti-BMZ antibodies on immunofluorescence studies, although no reactivity with either BP230 or BP180 was detected on ELISAs and immunoblot analyses.…”

Section: Kozo Yoneda 1 Toshio Demitsu 2 Maki Kakurai 2 Tae Narimentioning

confidence: 89%

“…GVHD reveals various skin lesions, such as maculo-papular rash, brownish pigmentation, and scleroderma (1). Although GVHD may present subepidermal blisters caused by vacuolar degeneration of basal cells, the association of bullous pemphigoid (BP) and GVHD is extremely rare (1).…”

mentioning

confidence: 99%

Detection of Apoptotic Keratinocytes in a Case of Bullous Pemphigoid Developed after Graft-versus-host Disease

Yoneda¹,

Demitsu²,

Kakurai³

et al. 2014

Acta Derm Venerol

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Graft-versus-host disease (GVHD) is a frequent complication following haematopoietic stem cell transplantation. GVHD reveals various skin lesions, such as maculo-papular rash, brownish pigmentation, and scleroderma (1). Although GVHD may present subepidermal blisters caused by vacuolar degeneration of basal cells, the association of bullous pemphigoid (BP) and GVHD is extremely rare (1).We report here a case of BP that developed 4 months after allogeneic bone marrow transplantation (BMT). Interestingly, histopathology revealed necrotic keratinocytes scattered in the spongiotic epidermis, composed of subepidermal blister roof. We further investigated the necrotic keratinocytes for the presence of apoptotic cells and cleaved caspase 3. CASE REPORTA 57-year-old Japanese woman was diagnosed with acute myelogenous leukaemia in November 2002. She achieved complete remission after chemotherapy with cytarabine, daunorubicin and gemcitabine. In June 2004, the patient underwent allogeneic BMT from her human leukocyte antigen (HLA)-identical older sister. GVHD prophylaxis was attempted with cyclosporine and short-term treatment with methotrexate. Complete remission of the acute myelogenous leukaemia and 100% donor chimerism were confirmed. In October 2004 (4 months after BMT), extensive exudative erythemas with blisters appeared over the patient's entire body surface (Fig. 1a). A biopsy from a fresh vesicle showed subepidermal blistering and moderate infiltration of both eosinophils and lymphocytes in both the dermis and the bulla (Fig. 1b). Dyskeratotic keratinocytes were observed in the epidermis at the roof of the bulla with spongiosis (Fig. 1b, c). Shrunken keratinocytes were also demonstrated in the blister roof of different blisters (Fig. 1d). Direct immunofluorescence of skin biopsy showed linear immunoglobulin G (IgG) deposition in the epidermal basement membrane zone (BMZ). Indirect immunofluorescence of normal human skin revealed circulating IgG anti-BMZ antibodies. Indirect immunofluorescence of 1 M sodium chloride (NaCl)-split skin sections showed IgG reactivity with the epidermal side of the split (Fig. 1e). No circulating anti-BMZ antibodies were detected in the older sister. BP180 and BP230 enzyme-linked immunosorbent assays (ELISAs) of the sera from the patient and her sister were negative. Immunoblot analysis of normal human epidermal extracts did not detect IgG antibodies to either BP180 or BP230. Immunoblot analysis of recombinant proteins of NC16a and C-terminal domains of BP180 showed negative results. Oral prednisolone, 1 mg/kg/day, was started, leading to complete disappearance of the skin lesions within one month. Oral prednisolone was discontinued 6 months later. One year later, the patient died from brain metastasis of leukaemia and progressive renal failure. In order to characterize the necrotic keratinocytes in the blister roof, we conducted transferase dUTP nick end labelling (TUNEL) staining with the ApopTag Plus Fluorescein In Situ Apoptosis Detection Kit (Merck Millipore, Darmstadt, Germany)...

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“…It is interesting to note that Grover's disease occurred within the first 2 weeks of bone marrow transplant in Harvell and colleagues and our study. This observation is important as bone marrow engraftment usually occurs between days 10 and 14 after the infusion of stem cells; hence, it is crucial to differentiate Grover's disease occurring at this time from early stage IV skin GVHD or toxic epidermal necrolysis (TEN) . Although they are clinically different, physicians and pathologists might mistakenly misdiagnose Grover's disease as a severe form of GVHD due to the vesicular and crusted clinical appearance together with the acantholytic findings in the histopathology.…”

Section: Discussionmentioning

confidence: 99%

“…The typical histological features of Grover's disease are acantholysis, dyskeratosis and suprabasal clefting. Dyskeratosis is also a prominent feature of chemotherapy‐induced cutaneous toxicity, GVHD and engraftment syndrome, while clefting can be seen in grade III and IV GVHD as well as in TEN . Acantholysis is an unusual finding in any of these differential diagnoses, and only Grover's disease features suprabasal clefting and acantholysis.…”

Section: Discussionmentioning

confidence: 99%

Transient acantholytic dyskeratosis (Grover's disease) after bone marrow transplantation

2016

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Cutaneous eruptions in recipients of allogeneic haematopoietic stem cell transplantation (AHSCT) are frequent, and common aetiologies include graft-versus-host disease (GVHD), drug reactions, viral infections and engraftment syndrome. Transient acantholytic dermatosis or Grover's disease has been described in oncology patients and it is rarely reported after AHSCT. However, this benign and self-limiting condition should be histologically distinguished from other, more serious entities, mainly stage IV GVHD, in order to avoid inappropriate treatment with corticosteroids and intensive immunosuppression.

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Stage IV cutaneous acute graft-versus-host disease. Clinical and histological study of 15 cases

Abstract: Stage IV cutaneous aGVHD is a severe and unusual complication after haematopoietic stem cell transplantation. Prognosis is poor with a very high mortality rate, although the cause of death is varied and not strictly linked to the cutaneous disease.

Cited by 13 publications

References 28 publications

Many faces of graft‐versus‐host disease

Many faces of graft‐versus‐host disease

Detection of Apoptotic Keratinocytes in a Case of Bullous Pemphigoid Developed after Graft-versus-host Disease

Transient acantholytic dyskeratosis (Grover's disease) after bone marrow transplantation

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