E-IJD CASE REPORT
|Year : 2015 | Volume
| Issue : 5 | Page : 525
|Lichenoid variant of chronic cutaneous graft versus host reaction post blood transfusion: A rare event post blood transfusion
Pushpa Kodipalya Ramakrishnaiah, Archana Lakshman, Sacchidanand Sarvajnamurthy Aradhya, Nataraja Holavanahally Veerabhadrappa
Department of Dermatology, Venereology and Leprosy, Bangalore Medical College and Research Institute, Rajiv Gandhi University of Health Sciences, Bangalore, Karnataka, India
|Date of Web Publication||4-Sep-2015|
Pushpa Kodipalya Ramakrishnaiah
d/o Ramakrishnaiah, No. 35, 1st D Main, BSK-3rd Stage, Girinagar-2nd Phase, Bangalore - 560 085, Karnataka
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Chronic graft versus host disease (GVHD) is a less frequently seen disease that occurs post solid organ or bone marrow transplantation. Chronic GVHD occurring post blood transfusion is an even more uncommon disease. It can present either as a lichenoid disease or as a sclerodermatous disease involving multiple systems. In this article, we report a case of chronic graft versus host reaction occurring in skin secondary to blood transfusion.
Keywords: Chronic cutaneous Chronic graft versus host disease, lichenoid Chronic graft versus host disease, post blood transfusion Chronic graft versus host disease
|How to cite this article:|
Ramakrishnaiah PK, Lakshman A, Aradhya SS, Veerabhadrappa NH. Lichenoid variant of chronic cutaneous graft versus host reaction post blood transfusion: A rare event post blood transfusion. Indian J Dermatol 2015;60:525
|How to cite this URL:|
Ramakrishnaiah PK, Lakshman A, Aradhya SS, Veerabhadrappa NH. Lichenoid variant of chronic cutaneous graft versus host reaction post blood transfusion: A rare event post blood transfusion. Indian J Dermatol [serial online] 2015 [cited 2021 Jul 23];60:525. Available from: https://www.e-ijd.org/text.asp?2015/60/5/525/159667
What was known?
- GVHD is most commonly known to occur following bone marrow/ solid organ transplantation.
- Post blood transfusion GVHD is mostly acute.
- Chronic GVHD post blood transfusion is very rarely reported.
| Introduction|| |
Graft versus host disease refers to the inflammatory and/or fibrosing manifestations that may arise at various times after transplantation of any organ containing lymphoid cells, which react against and damage tissues in the immunocompromised host. 
The GVHD syndrome has traditionally been subdivided into two syndromes: Acute GVHD and chronic GVHD. ,,, Graft versus host reaction (GVHR) is the expression of GVHD in a specific organ.
Transfusion-associated (TA) GVHD is a rare but probably underdiagnosed disorder, which, although usually fatal, may evolve into chronic graft-versus-host disease. 
| Case Report|| |
A 55-year-old female presented with complaints of increased pigmentation all over body since 4 years. The pigmentation initially started over right thigh and later spread to involve the entire body within few months. The patient also gave history of hair loss and nail changes since 4 years.
The patient gave history of receiving 2 units of cross-matched, unrelated, compatible blood for low hemoglobin (7.5 g %) about 6 months prior to the onset of pigmentation. The details as to the cause of anemia were not available.
The patient had attained menopause about 15 years back with no history of irregular menses or menorrhagia previously. She gave no history suggestive of any other comorbid illness in the past.
Cutaneous examination revealed generalized xerosis, patchy hyperpigmentation over face and forearms. Reticular hyperpigmentation was present elsewhere on the body. Palms and soles showed reticular hyperpigmentation with atrophic skin over digits [Figure 1]a, b and [Figure 2].
|Figure 1: (a): Reticulate hyperpigmentation present all over the body - posterior aspect. (b): Reticulate hyperpigmentation present all over the body - anterior aspect|
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Oral cavity showed reticular hyperpigmentation over buccal mucosa [Figure 3]. Patchy hyperpigmentation was found over hard palate and labia minora. Hair over the scalp was sparse and lateral eyebrows were lost [Figure 4]. Nails showed longitudinal ridging, distal niche, pterygium formation and atrophic changes [Figure 5].
|Figure 4: Non-scarring diffuse alopecia over scalp, reticulate hyperpigmentation over the face|
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|Figure 5: Distal niche, longitudinal ridging and pterygium over finger nails|
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Dermatoscopic study of pigmentation showed reticular pattern with dark brown-black pigment granules concentrating more at the corners of the network.
Based on history and clinical features, differential diagnoses of lichen planus pigmentosus, connective tissue disease and chronic graft versus host disease were considered and relevant investigations were done.
Investigations showed microcytic hypochromic anemia with hemoglobin of 9.5 g%, raised ESR (50 mm/hr), reactive CRP with negative ANA and RA factor. Her liver function tests, renal function tests, random blood sugar, serum calcium, uric acid, and thyroid profile were within normal limits. Her HIV1 and 2, HbsAg and VDRL were non-reactive. Ultrasound abdomen showed fatty liver. Cervical spine X-ray showed cervical spondylosis.
Histopathological examination showed thick basket weave and laminated orthokeratotic stratum corneum, flattened epidermis, focal hypergranulosis, basal cell vacuolization, individual necrotic keratinocytes at dermoepidermal junction and thick, innumerable melanophages with sparse lymphocytic infiltrate in widened papillary dermis [Figure 6] and [Figure 7].
|Figure 6: Histopathology × 10× (H and E) - thick basket weave, laminated orthokeratotic stratum corneum, flattened epidermis, focal hypergranulosis, basal cell vacuolization, individual necrotic keratinocytes at dermoepidermal junction and thick, innumerable melanophages with sparse lymphocytic infiltrate in widened papillary dermis|
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|Figure 7: Histopathology × 40× (H and E) - prominent orthokeratosis, individual necrotic keratinocytes, basal cell vacuolization|
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In the background of history of blood transfusion, onset of symptoms after 6 months of blood transfusion, clinical features and histopathologic features, a diagnosis of lichenoid variant of chronic cutaneous graft versus host reaction was made.
The patient was started on oral prednisolone 40 mg OD and azathioprine 50 mg OD, topical emollients and advised regarding photoprotection. However, the patient failed to follow up after starting treatment.
| Discussion|| |
GVHD occurs when immunocompetent T cells from a donor recognize and react against "foreign" tissue antigens in an immunocompromised host.  It may be the result of autoreactive T cells that escape negative selection in the thymus which has been damaged by preconditioning treatment, acute GVHD and/or age-related atrophy. The Th2 immune responses of these donor-derived CD4+ T cells then stimulate host B cells to synthesize autoantibodies.  In addition, IFN production by activated T cells induces HLA-DR expression on keratinocytes, making them targets for a similar reaction. ,
It is commonly observed after allogeneic bone marrow transplantation, (regularly used in the management of leukemias, lymphoma, immunodeficiency and inborn errors of metabolism), but TA GVHD is only rarely reported. TA GVHD is recognized to occur following transfusion of blood, after materno fetal transfer of lymphoid cells, and peripheral blood stem cell transfer.  Although early reports of TA GVHD were recognized in immunocompromised hosts, more recent cases have been documented in immunocompetent transfusion recipients. It has been documented after transfusion of unirradiated blood components, whole blood, fresh (nonfrozen) plasma, red blood cells, and platelets.  Transfusions from donors homozygous for an HLA haplotype to a recipient sharing this haplotype may predispose to TA GVHD in immunocompetent patient. ,,
There is an extremely high fatality rate for established acute TA GVHD, reaching 90% in some reports.  Because of the very high early mortality, chronic GVHD secondary to blood transfusion has only rarely been reported. 
Chronic GVHD develops in 30-40% of allograft recipients. It may appear de novo, or following acute GVHD, in continuity or after a variable symptom-free period.  The early phase generally appears up to the 100 th post-transplant day. 
It is usually a multisystem disease; localized disease also occurs, in which individual organs (usually skin or liver) are affected. The severity of individual organ involvement does not correlate well with the overall survival; the patient's functional performance is a better indicator of survival. ,
The skin is affected in 90%-100% of subjects with chronic GVHD. It can develop spontaneously or be triggered by several events, notably UV irradiation, physical trauma, zoster, or even Borrelia infections. 
The two main types of cutaneous manifestations are lichenoid and sclerodermatous lesions.  Lichenoid lesions occur early, typically on periorbital skin, ears, palms, and soles. A slowly progressive erythematous rash on the face, palms and soles becomes lichenoid, with changes resembling lichen planus in many sites. Thinning of the nails, pterygium formation, phimosis, or vaginal strictures may also develop. Oral involvement is very common, with areas of erythema and atrophy, lichenoid or hyperkeratotic plaques, ulceration, and atrophic glossitis. 
Reticulate patchy hyperpigmentation and, less commonly, hypopigmentation, poikiloderma, vitiligo (which may be total  ), erythema, atrophy, alopecia, multiple follicular papules, deep ulcerations of the buttocks and legs, and dystrophic nail changes are other features. 
Chronic GVHD can mimic other autoimmune connective tissue disorders, apart from systemic sclerosis. 
Both acute and chronic GVHD cause an interface dermatitis which may be a lichenoid lymphocytic infiltrate or predominantly vacuolar damage of basal cells. Lymphocytic "satellitosis" is particularly suggestive of GVHD, although no single histological feature is pathognomonic. ,
The lichenoid lesions are similar to acute GVHD lesions, with a superficial dermal lymphocytic infiltrate, moderate exocytosis, and a variable degree of keratinocyte necrosis.  Acanthosis, parakeratotic hyperkeratosis, and hypergranulosis are also seen. IgM may occur at the dermal-epidermal junction, with granular deposits of IgM, IgA and C3 in the walls of dermal vessels. There is associated microvascular disease mediated by cytotoxic T cells. 
Corticosteroids are the first choice for the treatment of chronic GVHD, but approximately 30% of patients require secondary systemic treatment.  The lichenoid variant is usually well-controlled with a combination of corticosteroids and cyclosporine. Cyclophosphamide, methotrexate, azathioprine, mycophenolate mofetil, pentostatin, or high-dose thalidomide and hydroxychloroquine may be used if the first-line therapy fails. PUVA photochemotherapy and narrow-band UVB phototherapy are other options for skin involvement, while extracorporeal photochemotherapy may improve cutaneous as well as systemic involvement 1],[8 . Granulocyte colony-stimulating factor,  antilymphocyte globulin,  tacrolimus,  biological therapies,  including etanercept,  and particularly rituximab,  may be helpful for steroid-resistant disease.
Patients with the lichenoid type of eruption have a worse prognosis, with 80% mortality at 10 years. 
Prevention includes gamma irradiation of the lymphocyte-containing blood products and the use of third- or fourth-generation leukoreduction filters, although not 100% efficacious.
| Conclusion|| |
Graft versus host disease can be induced when blood products containing viable lymphocytes engraft in recipients after transfusion. This syndrome is probably underdiagnosed and under reported. We hereby report a case of graft versus host disease occurring 6 months post blood transfusion. The disease affected skin, mucosa, hair and nails of the patient with no systemic symptoms and histology was suggestive of lichenoid GVHD.
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What is new?
- Chronic lichenoid GVHD, a disease usually seen post solid organ transplantation can rarely occur post blood transfusion.
- It can be limited only to skin, mucosa, nail and hair, without any systemic involvement and not causing much of functional impairment.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]