Drug rash with eosinophilia and systemic symptoms and graft-versus-host disease developing sequentially in a patient

Article (PDF Available)inClinical and Experimental Dermatology 34(2):199-201 · October 2008with34 Reads
Impact Factor: 1.09 · DOI: 10.1111/j.1365-2230.2008.02823.x · Source: PubMed
Abstract
We describe a case of drug rash with eosinophilia and systemic symptoms (DRESS) and graft-versus-host disease (GvHD) developing sequentially in a patient displaying reactivation of CMV. We discuss the possibility that similar pathogenic mechanisms may be involved in the development of DRESS and GvHD.

Full-text (PDF)

Available from: Salvador J Diaz-Cano
Drug rash with eosinophilia and systemic symptoms and
graft-versus-host disease developing sequentially in a patient
J. Natkunarajah, K. Watson, S. Diaz-Cano,* G. Mufti,† A. du Vivier and D. Creamer
Departments of Dermatology,*Histopathology and Haematological Medicine, King’s College Hospital, London, UK
Summary We describe a case of drug rash with eosinophilia and systemic symptoms (DRESS) and
graft-versus-host disease (GvHD) developing sequentially in a patient displaying
reactivation of CMV. We discuss the possibility that similar pathogenic mechanisms
may be involved in the development of DRESS and GvHD.
Drug rash with eosinophilia and systemic symptoms
(DRESS) is a severe acute drug reaction characterized by
a polymorphic skin eruption associated with fever,
eosinophilia, lymphadenopathy and multiorgan
involvement.
1
The development of DRESS has been
associated with reactivation of herpesviruses.
2,3
This
relationship is similar to the relationship between
herpesvirus reactivation and the development of graft-
versus-host disease (GvHD).
4
We report a case of DRESS
and GvHD developing sequentially in a patient display-
ing reactivation of cytomegalovirus (CMV).
Report
A 62-year-old white man with follicular non-Hodgkin’s
lymphoma underwent an allogeneic haemopoietic stem-
cell transplant (HSCT) from a matched unrelated donor,
after preparation with alemtazumab and fludarabine
treatment. After the transplant, the patient received
ciclosporin for GvHD prophylaxis and aciclovir for
prophylaxis against CMV reactivation. There was evi-
dence of previous CMV infection; however, this was
quiescent at the time of the transplant (pretransplant
CMV DNA load < 10 copies mL). The donor was
CMV-positive.
On day 18 post-HSCT, the patient became unwell
with a Gram-negative bacteraemia and was started on
tazocin, gentamicin, vancomycin and meropenem.
Three days later he developed a widespread, pruritic,
confluent erythema on the face, trunk and arms. There
was no mucosal involvement and the palms and soles
were spared.
Histology showed a spongiotic dermatitis with focal
parakeratosis, vesicle formation and prominent extrav-
asated red blood cells (Fig. 1a). There was evidence of
(a)
(b)
Figure 1 (a) Spongiotic dermatitis with focal parakeratosis and
vesicle formation, with prominent extravasated red blood cells;
(b) occasional necrotic keratinocytes without satellitosis.
Haematoxylin and eosin, original magnification (a,b) · 100.
Correspondence: Dr Janakan Natkunarajah, Department of Dermatology,
Amersham Hospital, Whielden Street, Amersham, HP7 0JD, UK.
E-mail: janakan@fsmail.net
Conflict of interest: none declared.
Accepted for publication 14 December 2007
Clinical dermatology Concise report doi: 10.1111/j.1365-2230.2008.02823.x
2008 The Author(s)
Journal compilation 2008 Blackwell Publishing Ltd Clinical and Experimental Dermatology
1
Page 1
occasional necrotic keratinocytes without satellitosis
with a chronic inflammatory cell infiltrate that included
eosinophils (Fig. 1b, arrowed). There were no histologi-
cal features of GvHD.
A drug-induced exanthema was diagnosed and vanco-
mycin was discontinued as it was thought to be the
causative agent. However, 19 days later the patient
remained unwell with fever, erythroderma, marked
oedema of the face and limbs and widespread lymphade-
nopathy. At this stage all antibiotics were discontinued.
Laboratory investigations showed eosinophilia of
6.9 · 10
9
L (normal range 0.0–0.4 · 10
9
L) and
abnormal liver-function results, with a raised alkaline
phosphatase of 170 IU L (30–130) and c-glutamyl
transpeptidase 183 IU L (1–55).
A diagnosis of DRESS was made, and the patient was
treated with prednisolone 40 mg daily and a potent
topical corticosteroid ointment. The erythema, oedema,
eosinophilia and liver-function abnormalities improved
over the next 3 weeks. Further tests performed at this
time showed evidence of recent CMV reactivation (CMV
DNA 2687 copies mL). The prednisolone was tapered
and discontinued and the patient was started on
vanciclovir 450 mg daily.
Seven weeks after the first eruption (day 71 post-
HSCT), the patient developed a new exanthema with a
(a)
(b)
(c)
(d)
CD7
CD8
Figure 2 Graft-vs.-host disease. (a) Vacuolar interface dermatitis with focal parakeratosis, spongiosis and lymphocyte exocytosis (hae-
matoxylin and eosin, original magnification · 400); (b) Spongiotic epidermis with necrotic keratinocyte and lymphocyte satellitosis (ha-
ematoxylin and eosin, original magnification · 400); (c) Intraepidermal lymphocytes demonstrate mature (CD7+) immunophenotype; (d)
Intraepidermal lymphocytes dsemonstrate cytotoxic (CD8+) immunophenotype (immunostaining, original magnification · 400).
2008 The Author(s)
2 Journal compilation 2008 Blackwell Publishing Ltd Clinical and Experimental Dermatology
DRESS and GvHD developing sequentially in a patient J. Natkunarajah et al.
Page 2
pruritic erythematous macular eruption involving the
trunk and a confluent erythema on the dorsal surfaces
of the hands and feet. Histology revealed prominent
lymphocyte exocytosis with basal vacuolation and
satellite-cell necrosis (Fig. 2a,b). The intraepidermal
lymphocytes showed a mature (CD7+) (Fig. 2d) and
cytotoxic (CD8+) (Fig. 2c) immunophenotype. These
features were indicative of GvHD. The patient was again
treated with prednisolone, resulting in rapid clearance
of the dermatosis.
We report an HSCT recipient who underwent CMV
reactivation with development of DRESS initially and
then acute GvHD. It is recognized that infection with, or
reactivation of, herpesviruses following HSCT is associ-
ated with a graft-versus-host reaction.
4
Maeda et al.
showed a temporal relationship between detection of
DNA of certain herpesviruses and appearance of GvHD.
5
In Maeda’s study, human herpesvirus 6 was identified
early (3–4 weeks post-transplant), whereas CMV and
EBV were detected at 2 months and 3 months post-
transplant, respectively, and coincided with the devel-
opment of GvHD.
5
The role of CMV specifically in the
induction of GvHD has been suggested by studies
showing that human leucocyte antigen (HLA)-DR7-
restricted CMV-specific CD4 T lymphocytes can display
specificity to the alloantigen HLA-DR4.
6
DRESS is a severe acute drug reaction characterized
by a polymorphic skin eruption associated with
fever, eosinophilia, lymphadenopathy and multiorgan
involvement.
1
Sulfonamide and anticonvulsants are
most often implicated as causal agents in DRESS, but
vancomycin is also a known drug culprit.
1,7
The
development of DRESS has been associated with
reactivation of CMV,
2
as well as other members of
the herpesvirus family.
3
In a recent issue of the British
Journal of Dermatology, Seishima et al.
8
noted positive
CMV DNA and an increased CMV IgG antibody titre in
all seven patients with DRESS and also showed a high
frequency of HHV6 and HHV7 positivity in this group
of patients. In the same issue Kano et al.
3
showed a
sequential pattern of herpesvirus reactivation in four
patients with DRESS, in which HHV6 and EBV were
reactivated early, followed by HHV7 and finally CMV.
This sequential cascade mirrors the pattern of virus
reactivation that has been described after bone-marrow
transplantation and HSCT.
9
Kano et al.
3
were also able
to demonstrate a relationship between various clinical
features of DRESS and reactivation of the different
human herpesviruses. These observations have led
researchers to believe that reactivation of human
herpesviruses is pathogenetic in the development of
both DRESS and GvHD, and that a sequential pattern
of viral expression is a common element in the
pathways of both disorders. However, we cannot
exclude the possibility that other herpesviruses may
have played a role in the development of both DRESS
and GvHD in our case, as titres of other herpesviruses
were not measured.
Kano et al.
10
were first to report a case of sclero-
dermoid GvHD after resolution of DRESS; however, it
remains unknown whether the herpesviruses were the
aetiological trigger. We describe another case of DRESS
and GvHD occurring consecutively in a patient who
displayed reactivation of CMV. We speculate that the
CMV upregulation may have had a role in triggering
both conditions in this individual.
References
1 Sullivan JR, Shear NH. The drug hypersensitivity
syndrome. Arch Dermatol 2001; 137: 357–64.
2 Aihara M, Sugita Y, Nagatani T et al. Anticonvulsant
hypersensitivity syndrome associated with reactivation
of cytomegalovirus. Br J Dermatol 2001; 144:
1231–4.
3 Kano Y, Hiraharas K, Sakuma K et al. Several herpesvi-
ruses can reactivate in a severe drug-induced multiorgan
reaction in the same sequential order as in graft-versus-
host disease. Br J Dermatol 2006; 155: 301–6.
4 Gratama JW, Middeldorp JM, Sinnige LG et al. Cytomega-
lovirus immunity in allogeneic marrow grafting. Trans-
plantation 1985; 40: 510–4.
5 Maeda Y, Teshima T, Yamada M et al. Monitoring of
human herpesviruses after allogeneic peripheral stem cell
transplantation and bone marrow transplantation. Br J
Haematol 1999; 105: 295–302.
6 Elkington R, Khanna R. Cross-recognition of human allo-
antigen by cytomegalovirus glycoprotein-specific CD4+
cytotoxic T lymphocytes: implications for graft-versus-host
disease. Blood 2005; 105: 1362–4.
7 Zuliani E, Zwahlen H, Gilliet F, Marone C. Vancomycin-
induced hypersensitivity reaction with acute renal failure:
resolution following cyclosporine treatment. Clin Nephrol
2005; 64: 155–8.
8 Seishima M, Yamanaka S, Fijisawa T et al. Reactivation of
human herpesvirus (HHV) family members other than
HHV-6 in drug-induced hypersensitivity syndrome. Br J
Dermatol 2006; 155: 344–9.
9 Maeda T, Teshima T, Yamada M, Marada M. Reactivation
of human herpesviruses after allogeneic peripheral blood
stem cell transplantation and bone marrow transplanta-
tion. Leuk Lymphoma 2000; 39: 229–39.
10 Kano Y, Sakuma K, Shiohara T. Sclerodermoid graft-ver-
sus-host disease-like lesions occurring after drug-induced
hypersensitivity syndrome. Br J Dermatol 2007; 156:
1061–3.
2008 The Author(s)
Journal compilation 2008 Blackwell Publishing Ltd Clinical and Experimental Dermatology
3
DRESS and GvHD developing sequentially in a patient J. Natkunarajah et al.
Page 3
  • [Show abstract] [Hide abstract] ABSTRACT: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, also referred to as drug-induced hypersensitivity syndrome, is a distinct, potentially life-threatening adverse reaction. It is seen in children and adults most often as a morbilliform cutaneous eruption with fever, lymphadenopathy, hematologic abnormalities, and multiorgan manifestations. Historically, it was most frequently linked with phenytoin and known as phenytoin hypersensitivity syndrome. However, because many other medications were found to produce the same reaction, another name was in order. Anticonvulsants and sulfonamides are the most common offending agents. Its etiology has been linked with lymphocyte activation, drug metabolic enzyme defects, eosinophilia, and human herpesvirus-6 reactivation. DRESS has a later onset and longer duration than other drug reactions, with a latent period of 2 to 6 weeks. It may have significant multisystem involvement, including hematologic, hepatic, renal, pulmonary, cardiac, neurologic, gastrointestinal, and endocrine abnormalities. This syndrome has a 10% mortality rate, most commonly from fulminant hepatitis with hepatic necrosis.
    No preview · Article · May 2013 · Journal of the American Academy of Dermatology
    0Comment72Citations
  • [Show abstract] [Hide abstract] ABSTRACT: Hematopoietic cell transplantation (HCT) is the preferred treatment for an expanding range of neoplastic and nonmalignant conditions. Increasing numbers of solid organ transplantations (SOTs) add an additional population of immunosuppressed patients with multiple potential neurological problems. While the spectrum of neurological complications varies with conditioning procedure and hematopoietic cell or solid organ source, major neurological complications occur with all transplantation procedures. This 2 part review emphasizes a practical consultative approach to central and peripheral nervous system problems related to HCT or SOT with clinical and neuroimaging examples from the authors' institutional experience with the following conditions: the diversity of manifestations of common infections such as varicella zoster virus, Aspergillus, and progressive multifocal leukoencephalopathy (PML), drug therapy-related complications, stroke mechanisms, the spectrum of graft versus host disease (GVHD), and neurologically important syndromes of immune reconstitution inflammatory syndrome (IRIS), posterior reversible encephalopathy syndrome (PRES), and posttransplantation lymphoproliferative disorder (PTLD). These complications preferentially occur at specific intervals after HCT and SOT, and neurological consultants must recognize an extensive spectrum of syndromes in order to effect timely diagnosis and expedite appropriate treatment.
    No preview · Article · Aug 2013
    0Comment25Citations

Similar publications