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An insidious skin rash without itch

DAVIDE LONATI 1 , ARTURO ZANCAN 2 , ANDREA GIAMPRETI 1 , DIEGO SPARPAGLIONE 2 , CARLO ALESSANDRO LOCATELLI 1, and LUIGI MANZO 1

1 Pavia Poison Center and National Toxicology Information Centre – Toxicology Unit, IRCCS Maugeri Foundation and University of Pavia, Via Salvatore Maugeri 10, Pavia, Italy 2 Rehabilitation Unit, IRCCS Maugeri Foundation, Via Salvatore Maugeri 10, Pavia, Italy

Abstract A 74-year-old female with a 5-year medical history of breast infi ltrating lobular carcinoma was admitted to our Rehabilitation Unit ward for left hemiparesis secondary to neurosurgical removal of frontal and right parietal metastatic lesions. After the intervention, prophylactic treatment with the antiepileptic diphenylhydantoin 100 mg/tid was started. On 38th day of drug administration an erythema without itch appeared in jugular and parasternal region and absent in the clothing covered areas, suggesting a contact dermatitis. Next day, the erythema extended to the neck with poorly delineated red plaques. During the following 4 days the patient presented oral stomatitis with fetid breath, atypical targetoid and erythematous confl uenced macules. The clinical picture rapidly worsened with vesiculate, bullate lesions and frank skin erosions. The patient was sent to a Dermatology Burn Unit where a therapy with corticosteroids, antibiotics, fl uids, albumin and immunoglobulins was administrated. Complete clinical resolution was observed after 1 month without long-term sequelae. Toxic epidermal necrolysis (TEN) is a rare (incidence about 0.01%) adverse drug reaction related to idiosyncratic mechanism, burdened by a mortality rate ranging from 3.2 to 90%. In our patient, TEN covered 63% of body surface, a condition associated with a death risk of 58.3% according to the specifi c severity illness scale SCORTEN. The disease onset may be insidious, and it could appear as a skin rash without itch; the cutaneous manifestations appear quite lately, then the disease quickly progresses. Early recognition of the disease, especially in oncologic patients, is critical for effective management of this condition in terms of mortality reduction.

Keywords Skin; Anticonvulsant; Other

Case description

A 74-year-old female with a 5-year medical history of breast infi ltrating lobular carcinoma was admitted to our Rehabilitation Unit ward for left hemiparesis secondary to neurosurgical removal of brain frontal and right parietal metastatic lesions. After the intervention treatment with diphenylhydantoin 100 mg/tid was started as antiepileptic prophylaxis. Omeprazole, 40 mg/day, and dexamethasone, 8 mg/day, were also administered. On 38th day of treat-ment an erythema without itch appeared in jugular and parasternal region. Skin changes were absent in the clothing covered areas. Contact dermatitis was suspected and oral treatment with loratadine, 10 mg/day, was started. Next day, erythema extended to the neck with poorly delineated red plaques. Topical 0.2% dexamethasone was applied. During the following 4 days the patient presented oral stomatitis (Fig. 1A) with fetid breath, atypical targetoid and erythema-tous/violaceous confl uenced macules extending to the back

and to the face (Fig. 1B). The clinical picture rapidly wors-ened during the subsequent 3rd and 4th day with vesiculate, bullate lesions and frank skin erosions (Fig. 1C).

Laboratory investigations revealed white blood cell count 3.24 × 10 3 /mm 3 , hemoglobin 10.6 g/dL, serum albumin 3.1 g/dL, serum blood urea nitrogen 11 mmol/L, serum sodium 127 mmol/L. Serum glucose (5.8 mmol/L), creatinine (0.7 mg/dL), AST (18 IU/L), ALT (20 IU/L), potassium (3.8 mmol/L) and platelet count (227 × 10 3 /mm 3 ) were normal.

Diagnosis and discussion

Toxic epidermal necrolysis

TEN is a severe adverse drug-reaction related to idiosyn-cratic mechanism, characterized by low incidence (0.01%) but burdened by a mortality rate ranging from 3.2 to 90%. 1,2 TEN differs from Stevens – Johnson Syndrome (SJS) based on quantitative evaluation of total body surface area (TBSA) involvement: cases with more than 30% TBSA involvement are indicated as TEN, while SJS represents cases of less 10%; those cases with 10 – 30% are defi ned SJS – TEN ‘ overlap ’ . TEN may develop after administration of a wide range of drugs including different classes of anti-bacterial agents (sulfonamides, quinolones tetracyclines and

Clinical Toxicology (2012), 50, 149–150

Copyright © 2012 Informa Healthcare USA, Inc.

ISSN: 1556-3650 print / 1556-9519 online

DOI: 10.3109/15563650.2011.642802

IMAGES

Received 20 October 2011 ; accepted 14 November 2011

Address correspondence to Dr. Davide Lonati, IRCCS Maugeri Founda-tion and University of Pavia, Pavia Poison Center and National Toxicology Information Centre – Toxicology Unit, Via Salvatore Maugeri 10, Pavia, 27100 Italy. E-mail: davide.lonati@fsm.it

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Clinical Toxicology vol. 50 no. 2 2012

150 D. Lonati et al.

beta-lactam antibiotics), anticonvulsants (such as phenytoin, phenobarbital and carbamazapine), anti-viral agents (e.g. nevirapine, abacavir), non-steroidal anti-infl ammatory drugs (particularly oxicams), allopurinol and lamotrigine. 1 In our patient, cutaneous changes suggestive of TEN developed after administration of diphenylhydantoin. Serum diphenyl-hydantoin levels were 11.4 μ g/mL (therapeutic range 10 – 20 μ g/mL). Treatment with diphenylhydantoin was discontin-ued on 40th day and replaced with levetiracetam 500 mg/tid. Differential diagnosis between TEN and paraneoplastic pemphigus was initially considered. A skin biopsy sample was sent to the Dermatology Department and the results were positive for TEN. The Nikolsky ’ s sign (epidermal separation induced by gentle lateral pressure on the skin surface) was not tested because of the rapid worsening of skin lesions and blisters onset. The patient was sent to a Dermatology Burns Unit where methylprednisolone (80 mg/day), teicoplanine (400 mg/day), fl uids up to 3000 mL/day (2500 mL sodium chloride 0.9% and 500 mL dextrose 5%), electrolytes (40 mEq/day), albumin and immunoglobulins were administered.

A complete clinical resolution was observed after 1 month without long term sequelae.

In our patient TEN covered 63% of body surface, a condi-tion linked to an estimated mortality rate of 58.3% according to the severity illness scale known as SCORTEN. 3 In TEN, the disease onset may be insidious appearing as a skin rash without itch; the cutaneous manifestations develop quite lately, associated with rapid progression of the disease.

Recognition of drug-related TEN is primarily based on the time course of symptoms that usually develop 1 – 3 weeks after initial exposure to the suspected drug. 1 While several observations have indicated the involvement of immunologi-cal mechanisms in the pathophysiology of TEN, the prompt withdrawal of the causing drug and the tailored medical man-agement as for burned patient are the main evidence-based therapies. 1 Immunomodulators (cyclosporine, cyclophosph-amide), plasmapheresis and intravenous immunoglobulins have been used in individual cases but the validity of these treatments is uncertain. 1,2 Early recognition of the disease remains a crucial requisite for effective management and reduction of the mortality risk in TEN patients.

Declaration of interest

The authors report no confl icts of interest. The authors alone are responsible for the content and writing of the paper.

References

Lissia M, Mulas P, Bulla A, Rubino C. Toxic epidermal necrolysis 1. (Lyell ’ s disease). Burns 2010; 36:152 – 163. Worswick S, Cotliar J. Stevens-Johnson syndrome and toxic epider-2. mal necrolysis: a review of treatment options. Dermatol Ther 2011; 24: 207 – 218. Bastuji-Garin S, Fouchard N, Bertocchi M, Roujeau JC, Revuz J, 3. Wolkenstein P. SCORTEN: a severity-of-illness score for toxic epi-dermal necrolysis. J Invest Dermatol 2000; 115:149 – 153.

Fig. 1. (A) Figure showing initial oral stomatitis and skin erosions of the face. (B) Atypical targetoid and erythematous/violaceous confl uenced macules extending to the upper limb and to the back. (C) Clinical worsening with vesiculate and bullate lesions and frank skin erosions diffusively extended to the back.

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