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648 Letters
fig. 2 Blood electrophoresis.
given twice per day for 4 days with a 6-week pause. The ulcer
was cured within 8 weeks by suppression of the monoclonal
component and thus, elimination of hyperviscosity.
This case is special from several points of view. Authors have
not found any reference in the literature about leg ulcer ori-
ginated from multiple myeloma associated with hyperviscosity
until now. The incidence of multiple myeloma (MM) in Europe
is 2.5–3/100 000. One percentage of malignancies and 10%
of haematologic malignancies represent multiple myeloma
(Kahler’s disease). The most frequent is echymosis without
thrombocytopaenia (10%). Extramedullar plasmocytomas occur
in 4% of patients. Amyloidosis was detected in 1% and even
more rarely found was leucocytoclastic vasculitis proved with
biopsy and histology.3
The main reason for the development of ulcer, as shown in
our case report, is assumed to be the elevated plasma viscosity
maintained by monoclonal gamma globulin-producing plasma
cells. Indirect proof is that after the beginning of the adequate
therapy for MM resulted wound sanation within a short period
of time and the ulcer epithelization advanced in tight relation
with the MM laboratory parameters (plasma viscosity, level of
gamma globulin), which were monitored during the therapy.
The patient has been free of symptoms for more than 3 years
now. Her haematologic status is under control.
A Bagó,†* K Schweitzer,‡ M Kiss,§ J Fûrész,‡ A Vajda,†
JM Baló-Banga†
†Department of Dermatology Central Army Hospital Budapest,
‡Department of Pathophysiology Institute of Sanitary Regulations, §1st
Department of Internal Medicine Central Army Hospital Budapest,
*Corresponding author: 1137. Budapest Róbert Károly körút 44, Hungary,
tel. +3613500611; fax +361392392915; E-mail: bagoandrea@yahoo.com
© 2005 European Academy of Dermatology and Venereology JEADV (2005) 19, 638–659
References
1 Baló-Banga JM, Bagó J, Juhász Zs. Factors influencing the
recurrency rate of different etiological type of crural ulcers.
Érbetegségek 2001; 4: 119–127.
2 Ciepluch H, Zaucha JM, Lysiak-Szydlovszka W. The level of
erythropoietin in patients with anaemia and myeloma multiplex
treated with erythropoietin. Pol Arch Med Wewn 1995; 94: 153–158.
3 Kois JM, Sexton FM, Lookingbill DP. Cutaneous manifestations of
multiple myeloma. Arch Dermatol 1991; 127: 69–74.
4 Neubauer RL, Morris GG. Plasmapheresis: first year experience at
Humana Hospital-Alaska. Alaska Med 1990; 32: 138–140.
5 Rajkumar SV, Gertz MA, Kyle RA. Current therapy for multiple
myeloma. Mayo Clin Proc 2002; 77: 813–822.
DOI: 10.1111/j.1468-3083.2005.01223.x
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Letters
? 2005
18etters
LET T ERS
Vancomycin-induced drug hypersensitivity
syndrome
To the Editor
Vancomycin has rarely been reported to cause drug hyper-
sensitivity syndrome (DHS). Purpuric skin lesions, progression
of the reaction even after withdrawal of the drug, and exacerbations
during steroid tapering were striking features of our case with
vancomycin-induced DHS.
A 56-year-old White woman with adult respiratory distress
syndrome induced by bile aspiration following a cholesistec-
tomy operation, developed tracheal stenosis upon which tra-
cheostomy was performed. As her tracheal and blood cultures
grew methicillin-resistant Staphylococcus aureus, vancomycin
2 g/day i.v. was started. On the 20th day of vancomycin

fig. 1 Diffuse purpuric and partially maculopapular rash on trunk, extremities
and hands. Note the atypical targetoid lesions on the lateral aspect of the
right index finger.
therapy, she developed fever (up to 39.4 °C) and maculo-
papular rash on the trunk and pharyngitis. As repeated tracheal
and blood cultures were negative, vancomycin was stopped.
A single dose of amoxicillin clavulanate, two doses of cipro-
floxacin and dipyrone were given empirically for high fever.
However, fever persisted, and diffuse facial and periorbital
oedema occurred. The maculopapular rash became generalized,
and progressed into purpuric lesions. Additionally, palmar
purpuric targetoid type lesions developed within a few days
(fig. 1). Mucosal lesions were absent. Histopathology of the
palmar purpuric targetoid lesions showed scattered necrotic
keratinocytes in the epidermis, diffuse basal vacuolar changes,
lymphocytic infiltration and oedema in the papillary dermis
with marked erythrocyte extravasation; suggesting the
diagnosis of purpuric erythema multiforme.
Table 1 Characteristic features of drug hypersensitivity syndrome1,2 (Our patient’s findings are in italics)
Finding Incidence (%)
Fever 90 –100
Skin/mucosal lesions 90
Lymphadenopathy 70
Systemic involvement 60
Hematologic abnormalities 50
Others 21
© 2005 European Academy of Dermatology and Venereology JEADV (2005) 19, 638– 659
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Letters 649
Serum biochemistry revealed high levels of aspartate
aminotransferase (124 U / L), alanine aminotransferase (229 U / L),
lactate dehydrogenase (828 U /L), creatinine (1.8 mg /dL), and
blood urea nitrogen (BUN) (34 mg /dL). Leucocytosis (15010/
mm3) and eosinophilia (1396/mm3) were noted. Serology was
negative for Epstein-Barr virus IgM, and cytomegalovirus IgM.
Unfortunately, serum levels of vancomycin could not be obtained.
Methylprednisolone 80 mg/day i.v. was started. As the abnormal
laboratory findings normalized within 2 weeks of therapy, steroid
was decreased on a daily tapering dose (4–8 mg every 5–10 days),
and cessated after approximately 2 months. Erythematous exacer-
bations occurred in every tapering dose lasting for 1–2 days.
The patient was diagnosed as a case with DHS that is an
uncommon but severe, idiosyncratic drug reaction, defined by
a widespread and long-lasting maculopapular or erythematous
skin eruption often progressing to exfoliative dermatitis, with
fever, lymphadenopathy and visceral involvement (Table 1).1–3
Some authors propose the acronym ‘DRESS’ (drug rash with
eosinophilia and systemic symptoms) to name the hyper-
sensitivity syndrome. The main inducers are antiepileptics, i.e.
phenytoin, carbamazepine, lamotrigine, and phenobarbital,
whereas sulphonamides, dapsone, allopurinol, terbinafine,
minocycline, azathioprine and gold salts were other reported
causative drugs.1,4 As fever, pharyngitis and localized maculo-
papular rash developed under vancomycin therapy, we believe
that vancomycin is the most probable aetiologic agent in our
case.
Vancomycin, a narrow-spectrum antibiotic, has numerous
adverse skin reactions ranging from the most common red man
syndrome to urticaria, anaphylaxis, linear IgA bullous disease,
acute generalized exanthematous pustulosis, exfoliative
dermatitis, exanthems, lupus erythematosus, vasculitis,
characteristics
Range between 38 °C and 40 °C
Intermittent/spiky
Maculopapular/morbilliform (most common)
Erythema multiforme
Purpuric lesions
Stevens–Johnson syndrome, toxic epidermal necrolysis (mucosal lesions)
Exfoliative dermatitis/erythroderma
Pustular lesions (rare)
Periorbital/facial oedema (25%)
Pharyngitis (10%)
Localized/generalized
Hepatic/renal/pulmonary involvement
Leucocytosis, eosinophilia, atypical lymphocytes (rare)
Coagulopathy
Aplastic anaemia, Coombs (–) haemolytic anaemia, dyserythropoetic anaemia
Lymphoma (rare)
Myalgia, arthralgia

650 Letters
erythema multiforme, Stevens–Johnson syndrome, and toxic
epidermal necrolysis.5 There are only few reports on severe drug
reactions as a result of vancomycin almost exclusively published
in pharmacology journals.6 – 9 The majority of the reported
cases with vancomycin-induced drug reactions had severe
skin reactions like exfoliative dermatitis, Stevens–Johnson
syndrome, or toxic epidermal necrolysis (TEN).6 – 8 These cases
had many of the classic features associated with DHS. However,
the authors preferred to name these cases according to the
previously mentioned skin reaction patterns instead of using
the term of DHS or DRESS. Different types of skin involvement
including TEN, as the most severe form can be seen in DHS
(Table 1). On the other hand visceral involvement might
develop in patients with TEN;1 thus a clear distinction could not
be made between these two conditions in the reported cases
under the name of TEN.7,8
The reaction usually occurred 1–4 weeks after vancomycin
has started, and most of the patients had concomitant chronic
renal failure leading to persistent serum vancomycin levels even
after the cessation of the drug.6,7 Although serum levels could
not be obtained, high vancomycin levels as a result of renal
involvement and/or to the nephrotoxic effect of the drug, might
be the reason for the worsening of the clinical picture, even after
withdrawal of vancomycin and for erythematous exacerbations
during steroid tapering in our case. The need for high doses of
corticosteroids, the exacerbations of the reaction and the pro-
gression into fatal toxic epidermal necrolysis during steroid
tapering have been reported in previous cases with vancomycin-
induced drug reactions.7–9
In conclusion, vancomycin should also be considered among
the causative agents of DHS. Unlike most DHS inducers, the
reaction could progress even after cessation of vancomycin.
Corticosteroids are usually effective but high doses and slow
tapering are necessary to avoid exacerbations during therapy.
KD YazganoGlu,* E Özkaya, P Ergin-Özcan, N Çakar
Istanbul University, Istanbul Medical Faculty, Departments of
Dermatology and Anaesthesiology and Intensive Care, Istanbul, Turkey,
*Corresponding author: Istanbul Üniversitesi, Istanbul Tıp Fakültesi,
Dermatoloji Anabilim Dalı, 34093, Çapa, Istanbul/Turkey,
tel. +90 212 3224108; mobile +90 5322040018; fax +90 2126353107;
E-mail: karadidem@hotmail.com
References
1 Ghislain P-D, Roujeau J-C. Treatment of severe drug reactions:
Stevens–Johnson syndrome, toxic epidermal necrolysis and
hypersensitivity syndrome. Dermatol Online J 2002; 8: 5.
2 Handfield-Jones SE, Jenkins RE, Whittaker SJ, Besse CP, McGibbon
DH. The anticonvulsant hypersensitivity syndrome. Br J Dermatol
1993; 129: 175–177.
3 Vittorio CC, Muglia JJ. Anticonvulsant hypersensitivity syndrome.
Arch Intern Med 1995; 155: 2285 –2290.
© 2005 European Academy of Dermatology and Venereology JEADV (2005) 19, 638–659
14683083, 2005, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1468-3083.2005.01228.x by Cochrane Romania, Wiley Online Library on [10/11/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
4 Schlienger RG, Shear NH. Antiepileptic drug hypersensitivity
syndrome. Epilepsia 1998; 39: 3 –7.
5 Litt JZ ed. Drug Eruption Reference Manual 2000. Parthenon
Publishing Group, New York, 2000: 591–592.
6 Forrence EA, Goldman MP. Vancomycin-associated exfoliative
dermatitis. DICP Ann Pharmacother 1990; 24: 369 –371.
7 Hsu SI. Biopsy-proved acute tubulointerstitial nephritis and toxic
epidermal necrolysis associated with vancomycin. Pharmacotherapy
2001; 21: 1233 –1239.
8 Hannah BA, Kimmel PL, Dosa S, Turner ML. Vancomycin-
induced toxic epidermal necrolysis. Southern Med J 1990; 83:
720 –722.
9 Packer J, Olshan AR, Schwartz AB. Prolonged allergic reaction to
vancomycin in end-stage renal disease. Dial Transplant 1987; 16:
86 –88.
DOI: 10.1111/j.1468-3083.2005.01228.x
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Letters
? 2005
18etters
Yellow nail syndrome associated with sleep
apnoea
To the Editor
Yellow nail syndrome (YNS) is characterized by slow-
growing nails, which become thickened, without visible lunulae,
and with exaggerated lateral curvature and a yellowish discoloration.
In typical cases, YNS is associated with primary lymphoedema
and pleuro-pulmonary inflammatory disorders.1 Less commonly,
YNS may occur in association with other diseases. We report a
case of YNS in a patient with obstructive sleep apnoea (OSA).
A 60-year-old man was seen in our department for yellowish
discoloration and thickening of the fingernails and toenails
associated with nail growth arrest of 4-month duration. In
addition, the patient had a 6-month history of snoring, excessive
daytime somnolence and fatigue. On examination, all finger-
nails and toenails had yellowish, thickened appearance with
increased lateral curvature and absence of the cuticle (fig. 1a).
No lymphoedema of the extremities or the face, and no enlarged
lymph nodes and tonsillar hypertrophy were present. His body
mass index was 28.3. He was a heavy cigarette smoker until 10
years prior to examination. He had no past history of lym-
phoedema, infectious or inflammatory pleuro-pulmonary dis-
ease, and was taking no medications. Nail cultures for bacteria
and fungi were negative. Routine laboratory tests were within
normal limits. Blood gas analysis showed mild arterial hypox-
emia. X-ray of the chest, hands and skull, echocardiography and
respiratory function testing did not reveal abnormal findings.
Chest and sinus CT scan showed a modest bronchial and peri-
bronchial inflammatory disease. An overnight cardiorespiratory
polygraphy was performed with monitoring that included oronasal
airflow by thermistor, chest and abdominal respiratory movements,
tracheal sounds, cardiac frequency, oxygen saturation and body
position. Sleep data scored according to the Rechtschaffen and