eruption associated with amoxicillin in a patient with infectious mononucleosis

© 2003

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2003,

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, 553–555

553

A 9-year-old boy presented with a history of fever, malaise, and sore throat for 1 day. He

was seen by his family physician who diagnosed tonsillitis. The past medical history was

unremarkable. There was no previous history of allergy to medications. After a throat swab had

been taken and sent for bacterial culture, the patient was started on amoxicillin, 250 mg three

times daily.

Two days later, the child developed an extensive pruritic eruption over the body. We were

consulted at this point. On examination, the child was afebrile. His pulse rate was 74/min and

his blood pressure was 90/60 mmHg. An erythematous, maculopapular eruption was noted on

the face, neck, trunk, buttocks, and extremities (Fig. 1). The palms and soles were also involved,

but to a lesser extent. The pharynx and tonsils were erythematous. Yellowish exudates were

seen in the tonsillar area. There were shotty lymph nodes in the cervical area. The spleen and

liver were not palpable. The rest of the physical examination was normal.

A provisional diagnosis of infectious mononucleosis was made. In the meantime, the throat

swab culture came back as negative. Amoxicillin therapy was discontinued. Hydroxyzine

hydrochloride, 10 mg four times daily as required, was given to relieve the itchiness.

Laboratory investigations showed a hemoglobin of 125 g/L, white blood cell count of 12

×

10

9

/

L with 75% lymphocytes, 23% neutrophils, 5% monocytes, and 2% eosinophils, and a platelet

count of 200

×

10

9

/L. Many atypical lymphocytes were seen in the peripheral smear. Monospot

test was positive, confirming the diagnosis of infectious mononucleosis.

The child was reassessed 7 days later. By then, the pruritus had subsided and the eruption

had cleared without desquamation. The pharynx and tonsils looked normal and there was no

cervical lymphadenopathy.

The child was seen by his family physician 5 months later because of a left-sided earache.

He was diagnosed with left otitis media and was treated with amoxicillin, 250 mg three times

daily for 7 days. No skin eruption was noted with the use of amoxicillin on this occasion.

Blackwell Science, LtdOxford, UKIJDInternational Journal of Dermatology0011-9059Blackwell Science, 2002?

Cameo

Eruption with amoxicillin in infectious mononucleosis

Leung and Rafaat

Eruption associated with amoxicillin in a patient with infectious mononucleosis

Alexander K. C. Leung,

MBBS, FRCP (UK & Irel), FRCPCH, FRCPC

, and Massoud Rafaat,

MD, FRCPC, DTM, DCH (Lond)

From the Department of Pediatrics, University of Calgary and Alberta Children’s Hospital, Calgary, Alberta, Canada

Correspondence

Alexander K.C. Leung,

MBBS

,

FRCP

(UK & Irel), FRCPCH,

FRCPC

#200, 233-16 Avenue NW Calgary Alberta Canada T2T 5C7 E-mail: [email protected]

Discussion

Infectious mononucleosis is caused by Epstein–Barr virus(EBV).

1

Prodromal symptoms include malaise, fatigue, head-ache, arthralgia, and myalgia.

1

The classic features arefever, tonsillopharyngitis, and lymphadenopathy.

1

Hepat-osplenomegaly may also occur. An eruption is present in3–10% of cases.

2–5

The typical eruption is morbilliform,involving mainly the trunk, with sparing of the extremities.

6

A presumptive diagnosis of infectious mononucleosis may bemade from the presence of typical clinical findings with atypicallymphocytosis in the peripheral smear. The diagnosis can beconfirmed by serologic testing. Paul–Bunnell antibodies areimmunoglobulin M (IgM) antibodies detected by the Paul–

Bunnell–Davidsohn test for sheep red cell agglutination. Themonospot test, a rapid slide test, based on the agglutination ofhorse red cells, provides a more sensitive assay than doessheep red cells. Heterophile antibodies appear in over 90% ofolder children and adults with infectious mononucleosis, butin fewer than 50% of children under 4 years of age. Theseantibodies may not be detectable until the second week of theillness. EBV-specific antibody testing is useful to confirm anacute EBV infection, especially in heterophile-negative cases.The presence of EBV-specific IgM antibodies indicates arecent or current infection, whereas the presence of IgG anti-bodies to the viral capsid antigen (VCA) or nuclear antigen(EBNA) merely indicates an infection with EBV some time inthe past.

International Journal of Dermatology

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Amoxicillin rash in infectious mononucleosis

Leung and Rafaat

The incidence of eruption in patients treated with ampicil-lin ranges from approximately 2.5% to 7.5%.

7,8

The inci-dence of eruption in patients with infectious mononucleosiswho receive ampicillin at the same time is over 70%.

3,9,10

Inseveral studies, the incidence was close to 100%.

9,10

Patel

3

performed a retrospective study of 38 consecutive hospital-ized patients with infectious mononucleosis, and found thatone of 11 cases (9%) who received no antimicrobial, two of14 cases (14%) who received penicillin G, cloxacillin, or tet-racycline, and 13 of 13 cases (100%) who received ampicillindeveloped a skin eruption. Pullen

et al

.

10

reviewed the hospitalrecords of 184 patients admitted with a diagnosis of infec-tious mononucleosis and found that 18 of the 19 patients(95%) treated with ampicillin developed a skin eruption.

Amoxicillin is an analog of ampicillin. Information onamoxicillin-induced eruption in patients with infectiousmononucleosis has been limited to a few case reports.

6,11–13

To our knowledge, our patient is the youngest case reportedwith this complication.

No data regarding the incidence of skin eruption inducedby amoxicillin in patients with infectious mononucleosis isavailable. It is logical to presume that the findings and conclu-sions that apply to ampicillin would also apply to amoxicillin.

The ampicillin/amoxicillin-associated exanthem can bedistinguished from the spontaneous eruption of infectiousmononucleosis in that the former exanthem is more severeand generalized, involving the face, neck, trunk, extremities,and sometimes the palms and soles.

6

The drug-associatedexanthem is pruritic, typically does not present until 5–8 daysinto the antimicrobial course, and is usually of longer dura-tion, lasting approximately a week.

3

The present reportshows that amoxicillin-induced eruption can appear as earlyas 2 days after the start of medication.

Although the exact pathophysiologic mechanism for thedrug-associated eruption is not known, it has been shown

that patients with infectious mononucleosis do not spontane-ously produce antibodies to ampicillin.

14

An immuneenhancement or a decrease in tolerance of the immune systemto certain drugs following infectious mononucleosis is proba-bly responsible.

12

In the majority of cases, the drug-associatederuption is not a permanent phenomenon.

15

Nazareth

et al

.

15

studied 20 patients with an ampicillin-associated exanthemduring the course of infectious mononucleosis. These patientswere subsequently given two doses of ampicillin with an inter-val of 2 weeks between the doses. The mean interval betweenthe first test dose and the onset of infectious mononucleosiswas 10.3 months (range, 1–17 months). Of the two patientswho reacted to the test doses, one had a history of atopy andthe other had previously reacted to penicillin. It is conceivablethat ampicillin/amoxicillin-induced exanthem during theacute stage of infectious mononucleosis should not obviatesubsequent ampicillin/amoxicillin therapy, as illustrated inthe present case.

Acknowledgments

Miss Rowena Kai provided expert secretarial assistance andMr Sulakhan Chopra (University of Calgary Medical Library)helped in the preparation of the manuscript.

References

1 Leung AK, Pinto-Rojas A. Infectious mononucleosis.

Consultant

2000;

40

: 134–136.2 Crespin FH Jr, Gordon RC. Infectious mononucleosis

in the community hospital.

J Fam Pract

1983;

16

: 703–708.

3 Patel BM. Skin rash with infectious mononucleosis and ampicillin.

Pediatrics

1967;

40

: 910–911.4 Chetham MM, Roberts KB. Infectious mononucleosis in

adolescents.

Pediatr Ann

1991;

20

: 206–213.5 McCarthy JT, Hoagland RJ. Cutaneous manifestations of

infectious mononucleosis.

J Am Med Assoc

1964;

187

: 193–194.

6 Pauzek ME. Making a rash diagnosis: amoxicillin therapy in infectious mononucleosis.

Indiana Med

1990;

83

: 330–331.

7 Knudsen ET. Ampicillin and urticaria.

Br Med J

1969;

1

: 846–847.

8 Croydon EA, Wheeler AW, Grimshaw JJ,

et al.

Prospective study of ampicillin rash: report of a collaborative study group.

Br Med J

1973;

1

: 7–9.9 Brown GL, Kanwar BS. Drug rashes in glandular fever.

Lancet

1967;

2

: 1418.10 Pullen H, Wright N, Murdoch JM. Hypersensitivity

reactions to antibacterial drugs in infectious mononucleosis.

Lancet

1967;

2

: 1176–1178.11 Copeman PW, Scrivener R. Amoxicillin rash.

Br Med J

1977;

1

: 1354.12 Patel A. Amoxicillin hypersensitivity reaction in a patient

Figure 1 An erythematous maculopapular eruption on the extremities

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with infectious mononucleosis: a case report.

Conn Dent Stud J

1986;

6

: 12–13.13 Gibbs P. Treatment of patients with glandular fever

with ampicillin or amoxicillin.

Br Dent J

1984;

156

: 78.

14 Kluge RM, Waldman RH, Delafuente JC,

et al.

Ampicillin-specific antibody and delayed hypersensitivity skin tests to ampicillin in patients with acute infectious mononucleosis.

J Infect Dis

1982;

145

: 397.15 Nazareth I, Mortimer P, McKendrick GD. Ampicillin

sensitivity in infectious mononucleosis – temporary or permanent?

Scand J Infect Dis

1972;

4

: 229–230.

Cameo

Dyskeratosis congenita

Dyskeratosis congenita with esophageal and anal stricture

Ercan Arca,

MD

, Ahmet Tüzün,

MD

, H. Bülent Tastan,

MD

, Ahmet Akar,

MD

, and Osman Köse,

MD

A 20-year-old man presented with skin lesions on his forearms and legs that had started to

appear at 3 years of age. On exposure to the sun, his skin became red. He suffered from

dysphagia and dysdefecation. His parents’ marriage was not consanguineous, and they were

well. His five brothers and sister were also well. He stated that one of his aunt’s sons and his

uncle’s son had the same lesions, but we were unable to examine them.

Physical examination revealed a reticulated pattern of atrophy, pigmentation, erythema, and

telangiectasia on the neck (Fig. 1), shoulders, popliteal fossa, and limbs. Atrophic lesions were

also present on the extensor aspects of the elbow and knees, and on the dorsum of the proximal

and distal interphalangeal joints of both hands (Fig. 2). Oral mucosal examination showed

leukokeratosis on the dorsum and sides of the tongue. There was mild hyperkeratosis on the dorsum

of the feet and hands. Sclerodactyly of the hands and feet was also present. The patient had no

fingerprints. The nails were thickened and rough, and had longitudinal and transverse ridges. Hairs

on the legs, forearms, and trunk were sparse. There was no splenomegaly or genital abnormalities.

Laboratory tests were as follows (normal values in parentheses): white blood count, 10,000/mm

3

(4000–10,000/mm

3

), with 66% neutrophils and 34% lymphocytes; red blood cell count,

5.68

×

10

6

/

µ

L; hemoglobin, 10.6 mg/dL; hematocrit, 35.4%; mean corpuscular volume, 62.2 fL;

platelet count, 419

×

10

3

/

µ

L; erythrocyte sedimentation rate, 4 mm/h (0–13 mm/h); vitamin B

12

,

285 pg/mL (211–911 pg/mL); folic acid, 6.4 ng/mL (1.1–20 ng/mL); ferritin, 3.7 ng/mL (22–

322 ng/mL). There was mild anisocytosis, microcytosis, and hypochromic anemia in a peripheral

blood smear. Liver transaminase levels were normal. There was a mild monoclonal gammopathy,

with a serum immunoglobulin G (IgG) of 1630 mg/dL (normal, 751–1560 mg/dL) and

a C3 of 155 mg/dL (normal, 79.2–152 mg/dL). The IgM and IgA levels were normal.

Chest X-ray was normal, and there was no evidence of abnormal calcification on skull X-ray.

An upper gastrointestinal endoscopy demonstrated a stricture at the upper esophageal

sphincter. Esophagography clearly revealed an esophageal stricture at the proximal esophagus

(Fig. 3). Sigmoidoscopy could not be performed because of the significant anal stricture, nor

could a digital rectal examination.

Histopathology of a biopsy specimen from the skin of the shoulder showed flattening of the

epidermis, a mild infiltrate of chronic inflammatory cells and melanophages, and dilated

capillaries in the dermis.

Discussion

Dyskeratosis congenita (DC) (Zinsser–Engman–Cole syn-drome) is a rare, inherited multisystem disease with cutaneous,

mucosal, ocular, gastrointestinal, and hematologic abnormal-ities, and an increased incidence of cancer. X-linked recessive,autosomal dominant and autosomal recessive forms of thedisease are recognized.

1–5

The pathogenesis of DC is still

From the Departments of Dermatology and Gastroenterology, Gülhane Military Medical Faculty, School of Medicine, Etlik, Ankara, Turkey

Correspondence

Ercan Arca,

MD

Department of Dermatology Gülhane Military Medical Academy School of Medicine Etlik 06018 Ankara Turkey E-mail: [email protected]

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Leung and Rafaat

unclear and curative therapy is presently lacking. Digestivetract abnormalities have also been described.

6

Esophagealstricture is a rare finding.

5

More than 100 cases have been recorded in the literatureand, by November 1999, 92 DC families, comprising 148(127 male and 21 female) patients from 20 countries, hadbeen recruited to the DC Registry at the Hammersmith Hos-pital, London, UK.

2,4

Although the pathogenesis is unclear, since 1995, the DCRegistry has identified new features of DC, and has beenpivotal in the identification of the DKC1 gene, mapped toXq28, responsible for X-linked DC. The DKC1 gene iscomposed of 15 exons spanning 15 kb. The correspondingprotein, dyskerin, contains 514 amino acids with a predictedmolecular weight of 57 kDa. The wide range of abnormalitiesseen in patients with severe X-linked and classic DC suggestthat dyskerin has a functional role in many tissues, and this issupported by the ubiquitous expression of the DKC1 gene.

1,2

The most common features of DC are atrophy of the skin,reticulated hyperpigmentation, dystrophic nails, and oral

leukoplakia. During the first decade of life, patients developreticulated poikiloderma of sun-exposed areas, with hyper-pigmentation and, occasionally, bullae. The nail changes areusually the first to appear. Between the ages of 5 and 13 years,the nails become dystrophic and are shed. Other skin abnor-malities include atrophic, wrinkled skin over the dorsum ofthe hands and feet, and hyperhidrosis and hyperkeratosis ofthe palms and soles with the disappearance of dermal ridges(absence of fingerprints). Multiple dental caries and early lossof teeth are common.

3,4

Joshi

et al

.

7

reported a 9-year-old Saudi girl with DC. Inaddition to the known manifestations of the disease, she hadtufts of hair on the limbs, and an early onset of keratinizedbasal cell papillomas on the trunk. Ho and Chang

8

reporteda 17-year-old Chinese girl with recessive inheritance of DC,who had brownish hyperpigmentation with striking reticula-tion on the neck, face, flexural areas, and anterior thighs,dystrophic nails with ridging and pterygium formation, and adystrophic tongue with patches of leukokeratosis.

Leukoplakia may be present in any mucosal site. It ofteninvolves the oral mucosa. Mucosal surfaces, such as theesophagus, urethra, and lacrimal duct, may become constrictedand stenotic, resulting in dysphagia, dysuria, and epiphora.

4

Roux-Serratrice

et al

.

6

reported a 27-year-old man who, inaddition to the usual manifestations of DC, had an esophagealweb. In 8% of patients, the gastrointestinal tract is involved.Enlargement of the liver and/or spleen, rare cases of livercirrhosis, portal hypertension, diverticula or strictures of theesophagus, gastroduodenitis, ulcers of the duodenum, andchronic diarrhea have been described.

9

In our patient,dysphagia was accounted for by an esophageal stricture.Other causes of dysphagia include peptic stenosis, Schatzki’sring, cancer, postsurgical and postradiation lesions, ingestionof caustic products, and esophageal web.

3

Esophageal stricture has been described mainly in chil-dren,

5,6

and cervical esophageal stricture has been considered

Figure 1 Patient’s neck showing reticulated, hyperpigmented, and atrophic skin lesions and telangiectasias

Figure 2 Thin and atrophic skin of the dorsum of the hands and dystrophic fingernails

Figure 3 Esophagographic image demonstrating an esophageal stricture at the proximal esophagus

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et al.

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to be an acquired lesion. Tonev

et al

.

10

reported a 23-year-oldwhite Cuban with DC. In addition to the triad of poikilo-derma, onychodystrophy, and leukoplakia, he had congenitalstenosis of the esophagus and extreme seborrhea of the scalp.In our case, there was no history of ingestion of causticmaterial or radiation. Therefore, we considered that theesophageal stricture could have been acquired. In all suchcases, treatment by dilatation has been successful. Berezin

et al

.

11

reported a 5-year-old boy with DC, who complainedof solid food dysphagia and frequent postprandial emesisbecause of esophageal narrowing. Esophageal dilatation wasperformed and the patient remained asymptomatic for 2 yearspostdilatation. Sawant

et al

.

12

reported an 8-year-old boy whocomplained of regurgitation of food, intermittent vomiting,recurrent upper respiratory tract infection, and progressivedysphagia. The patient’s barium swallow showed narrowingof the lower third of the esophagus, and the stricture wasdilated. Over a 6-month follow-up, dysphagia did not recur.In our case, because the stricture segment was too long toapply dilatation, and there were complications, such as perfo-ration and bleeding, we did not use dilatation treatment. Inaddition, the patient refused all therapeutic interventions.

Although gastrointestinal problems, including colitis andcongenital esophageal stricture, have previously been reported,

13

to our knowledge, anal stricture has not been reported previ-ously in association with DC. The anal stricture in our casewas so narrow that the patient could not defecate. Berezin

et al

.

11

reported that their case had proctitis, but no specifictherapy was instituted and symptoms did not progress overthe subsequent 1-year period. Brown

et al

.

13

reported thatthere was partial improvement of gastrointestinal findingswith corticosteroid treatment, but the response was variable.Because of the presence of the narrow anal stricture, we didnot perform sigmoidoscopy or any therapeutic intervention.

DC has a poor prognosis. The primary causes of death areinfections (approximately 35%), malignancies (approximately25%), and hemorrhage (approximately 15%). Therapeuticpossibilities are primarily palliative and are at presentunsatisfactory.

In DC, 59% of patients suffer from dysphagia and mosthave congenital stenosis or esophageal diverticulum.

13

Theselesions can undergo malignant transformation. Long-termfollow-up of these patients is required in order to detect

malignancy early. Thus far, the early establishment of thediagnosis and the consideration of complications, togetherwith the reasonable application of therapeutic measures, aremost important for a favorable influence on the course of thiscomplex disease.

References

1 Dokal I. Dyskeratosis congenita.

Br J Haematol

1999;

105 (Suppl. 1): 11–15.

2 Dokal I. Dyskeratosis congenita in all its forms. Br J Haematol 2000; 110: 768–779.

3 Harper JI. Genetics and genodermatoses. In: Champion RH, Burton JL, Burns DA, Breathnach SM, eds. Rook/Wilkinson/Ebling Textbook of Dermatology, 6th edn. London: Blackwell Science, 1998: 357–436.

4 Kraemer KH. Heritable diseases with increased sensitivity. In: Freedberg IM, Eisen AZ, Wolff K, et al., eds. Dermatology in General Medicine, 5th edn. New York: McGraw-Hill, 1999: 1848–1862.

5 Elliot MA, Graham GE, Bernstein M, et al. Dyskeratosis congenita: an autosomal recessive variant. Am J Med Gen 1999; 83: 178–182.

6 Roux-Serratrice C, Serratrice J, Escoffier JM, et al. Esophageal web in Zinsser–Engman–Cole–Fanconi disease. Gastrointest Endosc 2000; 52: 561–562.

7 Joshi RK, Atukorala DN, Abanmi A, Kudwah A. Dyskeratosis congenita in a female. Br J Dermatol 1994; 130: 520–522.

8 Ho CLY, Chang LY. Dyskeratosis congenita in an ethnic Chinese girl. Int J Dermatol 1996; 35 (9): 659–660.

9 Head G, Solder B, Weiss M, et al. Dyskeratosis congenita: multisystemic disorder with special consideration of immunologic aspects. Clin Pediatr 1998; 37: 521–530.

10 Tonev S, Pramatorov K, Daskorev L, Gadev A. Dyskeratosis congenita (Zinsser–Engman–Cole syndrome). Z Hautkr 1990; 65: 193–195 (Abstract).

11 Berezin S, Schwarz SM, Slim MS, et al. Gastrointestinal problems in a child with dyskeratosis congenita. Am J Gastroenterol 1996; 91: 1271–1272.

12 Sawant P, Chopda NM, Desai DC, et al. Dyskeratosis congenita with esophageal stricture and dermatological manifestations. Endoscopy 1994; 26: 711–712.

13 Brown KE, Kelly TE, Myers BM. Gastrointestinal involvement in a woman with dyskeratosis congenita. Dig Dis Sci 1993; 38: 181–184.

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eruption associated with amoxicillin in a patient with infectious mononucleosis

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