Erythema multiforme associated with Trichophyton mentagrophytes infection

638

© 2002 European Academy of Dermatology and Venereology

LETTERS

JEADV

(2002)

16

, 638–649

Blackwell Science, LtdOxford, UKJDVJournal of the European Academy of Dermatology and Venereology0926-99592002 European Academy of Dermatology and Venereology? 200216?LettersLettersLetters

Acne vulgaris as an immune reconstitution syndrome in a patient with AIDS after

initiation of antiretroviral therapy

To the Editor

Initiation of highly active antiretroviral therapy (HAART) in

patients with HIV usually leads to a decrease of plasma

HIV-RNA followed by an increase of CD4 T-helper cells.

Exacerbation or progression of other associated inflammatory

infections are well-known as immune reconstitution syn-

dromes under the improvement of immune system during HAART.

We report a reactivation of acne vulgaris in a patient with AIDS

after initiating HAART.

A 29-year-old Caucasian man presented to our department

with dyspnoe, fever, weakness, and weight loss (4 kg) during the

last 4 weeks. There were no pathological cutaneous findings at

the first examination. Sputum samples, arterial blood gas ana-

lysis (BGA), chest roentgenogram, and high resolution (HR) CT

scan were consistent with Pneumocystis carinii pneumonia

(PCP). HIV antibody testing was positive, laboratory examina-

tions revealed leucopenia (3530/mL), lymphopenia (810/mL),

a C-reactive protein of 23.0 mg/L, 10 CD4+ lymphocytes/mL,

253 CD8+ lymphocytes/mL, a CD4/CD8 ratio of 0.01 and a

HIV-1 RNA of 53 100 copies/mL. No other additional haema-

tological, biochemical or immunological abnormalities were

demonstrated. We initiated HAART with stavudin 40 mg,

lamivudine 150 mg and nelfinavir 1250 mg twice daily. Initial

treatment also included antibiotic therapy with cotrimoxazol

3840 mg twice daily oral for 21 days. After 14 days of treatment,

the patient showed clearance of all general symptoms.

Two months later the patient presented with comedones,

erythematous papules, and pustules on the forehead,

cheeks, and upper trunk. The distribution of the non-pruritic

lesions was predominantly follicular. Bacterial cultures of

papulopustules contents grew

Proprionibacterium acnes

.

The patient reported a history of acne vulgaris until he was

19 years old. On examination, he revealed a good response to

HAART with undetectable HIV-1 RNA (< 40 copies/mL),

154 CD4+ lymphocytes/mL, and 1735 CD8+ lymphocytes/mL.

Topical treatment with erythromycin led to a complete clear-

ance of skin lesions after 8 weeks.

Restitution of immune function under HAART can lead to

some adverse effects, because of improved immune response to

pathogens that are already present in the body. Such immune

inflammatory syndromes, e.g. herpes zoster, immune recovery

inflammatory folliculitis, CMV retinitis, toxoplasmosis, pro-

gressive multifocal leukoencephalopathy, hepatitis C, and

mycobacteriosis have been reported after initiating antiretro-

viral therapy.

1–4

HAART causes a rapid and early increase in

memory lymphocytes (CD45RO) and native cells (CD45RA).

In addition to the increase of CD4+ cells, also CD8+ cells

increase. This rapid rise of CD8+ cells before reconstitution

of the CD4 cell function has been accused to be a risk factor

for developing herpes zoster after beginning HAART.

5

Our

patient’s reactivation of acne occurred during a rise of CD8+

cells up to 1735/mL. Similar observations have been described

in HIV-infected patients presenting ‘immune recovery follicu-

litis’ under HAART.

3

Pruritic skin lesions involved the face and

upper trunk. These skin manifestations are possibly related to

an immune response against pathogens that are already present

in the skin, e.g. demodex folliculorum. The hair follicle is a

common reservoir for various micro-organisms. We hypothes-

ize that in our patient the restoration of immune response

against

Proprionibacterium acnes

could explain the reactivation

of acne vulgaris after initiating HAART. Regression of skin

lesions after topical erythromycin may suggest an underlying

immunopathological process.

A

Kreuter,

R

Schlottmann,

P

Altmeyer,

NH

Brockmeyer

Department of Dermatology, Ruhr-University Bochum, Gudrunstrasse

56, 44791 Bochum, Germany, tel. +49 234 509 3473;

fax +49 234 509 3475; E-mail: [email protected]

References

1 Behrens GM, Meyer D, Stoll M, Schmidt RE. Immune reconstitution

syndromes in human immuno-deficiency virus infection following

effective antiretroviral therapy.

Immunobiology

2000;

201

: 186–193.

2 Collazos J, Mayo J, Martinez E, Blanco MS. Contrast-enhancing

progressive multifocal leukoencephalopathy as an immune

reconstitution event in AIDS patients.

AIDS

1999;

13

: 1426–1428.

3 Bouscarat F, Maubec E, Matheron S, Descamps V. Immune recovery

inflammatory folliculitis.

AIDS

2000;

14

: 617–618.

4 Handa S, Bingham JS. Dermatological immune restoration syn-

drome: does it exist?

J Eur Acad Derm Ven

2001;

15

(5): 430–432.

5 Domingo P, Torres OH, Ris J, Vasquez G. Herpes zoster as an

immune reconstitution disease after initiation of combination

antiretroviral therapy in patients with human immunodeficiency

virus type-1 infection.

Am J Med

2001;

110

: 605–609.

16LetterLetterLetterxxxxx

Report of a case of Muir–Torre syndrome

To the Editor

Muir–Torre syndrome (MTS) is an autosomal dominant

genodermatosis, characterized by at least one single sebaceous

gland tumour and a minimum of one internal malignancy.

1

In

a recent review of the literature, Akhtar

et al

. found only 205

cases of MTS.

2

The most common presentation is sebaceous

tumours with a low-grade visceral malignancy.

1

JDV_653.fm Page 638 Friday, October 25, 2002 9:02 PM

Letters

639


JEADV

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, 638–649

We observed in 1998 a 71-year-old caucasian male with

multiple, rapidly growing haemorrhagic tumours in the left

frontoparietal region (fig. 1) that were recurrences of a

sebaceous carcinoma treated 2 months earlier by classic surgery

and radiotherapy (fig. 2). The man had no personal or family

history of cutaneous or visceral neoplasms, but he experienced

an acute episode of haematochesia, and colonoscopy evidenced

a colorectal adenocarcinoma 8 cm from the anus. Cervical

metastasis of the cutaneous sebaceous carcinoma were detected

and computed tomography scan showed lung and acetabular

metastases. Chromosomal studies to detect microsatellite

instability (MSI) on the visceral tumour were negative.

Chemosurgery without microscopic control with a 40%

zinc chloride paste was performed on the larger tumours and

cryosurgery with liquid nitrogen was used for the smaller ones.

Systemic chemotherapy with 5-fluorouracil (1000 mg/m

2

) and

cisplatin (100 mg/m

2

) was administered monthly and the

osseous metastasis was treated with external radiotherapy.

Complete necrosis of the cutaneous tumour was obtained, and

the cranial periosteum was exposed. Incisional biopsies of the

margins of the ulceration disclosed no tumour. 5-Fluorouracil

was administered for 18 months and the man is still alive

and well.

Accepted criteria for the diagnosis of the rare MTS

include the presence of at least one sebaceous tumour or

keratoacanthoma with sebaceous differentiation and a visceral

malignancy, or the report of a family history of MTS in a subject

with multiple keratoacanthomas and visceral malignancies, in

the absence of any known predisposing factor.

3

Our patient

fulfilled the diagnostic criteria for MTS. The colorectal carci-

noma diagnosed in our patient accounts for 51% of all primary

cancers in MTS subjects.

4

After gastrointestinal cancers the

next most frequent finding is genitourinary malignancies,

diagnosed in 22% of these subjects.

2

Breast and head and neck

cancers are other possible locations.

2

Sebaceous carcinoma is an uncommon malignant tumour

derived from the adnexal epithelium of sebaceous glands,

usually arising in the orbital region.

5

However, 25% of all

reported cases are extraocular,

6

implying a distinct risk of

aggressive behaviour.

5

In cases presenting sebaceous carcinoma, screening for inter-

nal malignancy should be performed to exclude the possibility

of MTS.

2

Sebaceous neoplasms precede or are concurrent with

the visceral cancer in 41% of these subjects patients and occur

afterward in 59% of cases of MTS.

4

Genetic studies have demonstrated MSI, which is a defect in

DNA replication, in the tumours of some subjects with MTS,

4

including this rare genodermatosis in the hereditary non-

polyposis colorectal cancer.

2,7

MSI is more frequently found in

the sebaceous tumours of MTS subjects or in those of immuno-

suppressed organ transplant recipients.

8

Subjects with MSI tend

to have prolonged survival after diagnosis of visceral malig-

nancies.

4

MSI was not found in the tumours of our patient.

In MTS, the neoplasms display a non-aggressive course,

although 60% of the patients present with metastatic disease.

3

The man in our case presented extensive and aggressive local

recurrence as well as lymphnode and visceral metastases.

Chemosurgery and cryosurgery are methods well known to

fig. 1 Multifocal sebaceous carcinoma: recurrence after radiotherapy and

classic surgery.

fig. 2 Lobules and nests of clear cells. Haematoxylin and eosin, original

magnification, × 40.


640

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, 638–649

dermatologists and were very efficient in this case. Chemosur-

gery without systematized microscopic control was developed

by Gonçalves and Cabral de Ascenção;

9

the method has an

extremely high cure rate for skin tumours (99.75% in 400 cases

published) and is effective, cheap and simple to do. Its value has

been recently reviewed, and it probably has immunogenic

properties.

10

Lymph node and visceral metastases also regressed

with chemotherapy.

In spite of the aggressive behaviour of the tumours in our

patient, multiple complementary therapies proved to be of

value in his survival.

Note added in proof: The patient died at the end of 2001, due

to metastatic colorectal cancer; sebaceous carcinoma did not

recur.

C

Moura,†*

MM

Pecegueiro,†

MF

Sachse,†

J

Amaro,†

I

Fonseca,‡

A

Fernandes,§

N

Vau§

Departments of

†

Dermatology,

‡

Pathology and

§

Medical Oncology of the

Instituto Português de Oncologia de Francisco Gentil, Rua Prof.

Lima Basto, 1099-023 Lisbon, Portugal.

*

Corresponding author,

tel. 351 21 7229800 (ext. 1346/1338); fax 351 21 7229886

References

1 Cohen PR, Kohn SR, Kurzrock R. Association of sebaceous gland

tumors and internal malignancy: the Muir–Torre syndrome.

Am J

Med

1991;

90

: 606–613.

2 Akhtar S, Oza K, Khan S

et al.

Muir–Torre syndrome: case report of

a patient with concurrent jejunal and ureteral cancer and a review

of the literature.

J Am Acad Dermatol

1999;

41

: 681–686.

3 Schwartz R, Torre DP. The Muir–Torre syndrome: a 25-year

retrospect.

J Am Acad Dermatol

1995;

33

: 90–104.

4 Honchel R, Halling KC, Rehman I

et al.

Microsatellite instability in

Muir–Torre syndrome.

Cancer Res

1994;

54

: 1159–1163.

5 Schwartz RA, Goldberg DJ, Mahmood F

et al.

The Muir–Torre

syndrome: a disease of sebaceous and colonic neoplasms.

Dermatologica

1989;

178

: 23–28.

6 Wick MR, Goellner JR, Wolfe JT III

et al.

Adnexal carcinomas of

the skin. Extraocular sebaceous carcinomas.

Cancer

1985;

56

:

1163–1172.

7 Kruse R, Rutten A, Hosseiny-Malayeri HR

et al.

‘Second hit’ in

sebaceous tumors from Muir-Torre patients with germline

mutations in MSH2: allele loss is not the preferred mode of

inactivation.

J Invest Dermatol

2001;

116

(3): 463–465.

8 Harwood CA, Swale VJ, Bataille VA

et al.

An association between

sebaceous carcinoma and microsatellite instability in

immunosuppressed organ transplant recipients.

J Invest Dermatol

2001;

116

(2): 246–253.

9 Gonçalves JCA. An attempt at reducing pain in cancer patients

treated by chemosurgery without systematised microscopic control.

Skin Cancer

1998;

13

: 145–161.

10 Kirn TF. Using zinc chloride paste before Mohs enhances outcome.

Skin Allergy News

2000;

February

: 6.

16LetterLetterLetter

‘

Nocardia asteroides

’ mycetoma of the foot

To the Editor

Mycetoma is a granulomatous infection characterized by

subcutaneous tumid swellings, usually affecting the lower limbs

(around the ankle) with formation of sinuses that generally

discharge pus containing grains of different colours. Several

aetiological agents,

1–4

including

Nocardia asteroides

have been

incriminated. The current case is yet another example where

N. asteroides

(type VI) was identified as the aetiological

agent.

A 51-year-old farmer from the Indian state of Bihar pre-

sented with multiple draining sinuses on the dorsum, ankle and

sole of his right foot. He used to work barefooted in a field. The

initial lesion started in the central area of the sole of the right

foot. The nodule subsided on its own in 2 months, but

reappeared again 1 month later and was larger and painful. In

due course, multiple swellings appeared on the sole and dorsum

of the right foot discharging pus. The man had been treated

from that time on with several courses of antibiotics without

any beneficial effect. At the time of our examination, he had

severe pain and disability of the right foot due to multiple

swellings. Examination of the affected site revealed an irregular

swelling in and around the right ankle joint, with swelling of

the dorsum and sole of the foot. There were conspicuous

multiple sinuses discharging blood-stained purulent material

(fig. 1), but the grains were not visible in the discharge on naked

eye examination. An X-ray of the foot revealed soft tissue

swelling only.

The yellowish-white discharge from the draining sinuses

cultured on Sabouraud dextrose agar/glucose nutrient agar

yielded a pure culture of

Nocardia

, tentatively identified

as

N. asteroides

on the basis of preliminary biochemical tests.

The colonies of the isolate were initially white, but soon turned

orange with a folded moist surface. Smears of the growth

stained by Kinyouns’ cold acid-fast stain revealed partially

acid-fast, branching, slender hyphae with coccobacillary

fragments. The isolate was not positive for decomposition of

adenine, xanthine, tyrosine, hypoxanthine or casein. It was

also negative for urease, arysulphatase and for acid production

from cellebiose and inositol as tested up to 2 weeks. Growth

was positive at 46

°

C. The isolate was identified as

N. asteroides

on the basis of detailed biochemical tests and cell wall

analysis.

5,6

It was assigned to the type VI on the basis of

in vitro

antimicrobial sensitivity pattern.

Haematoxylin–eosin-stained serial tissue sections prepared

from the representative lesion were examined. A few of the

sections revealed non-specific granulation tissue, composed of

neutrophils, eosinophils, lymphocytes, plasma cells, histiocytes

and fibroblasts. In addition small actinomycotic granules were

identified in the granuloma. The granules were homogeneous

in the centre and had radiating, branching filaments at the

periphery. They were basophilic and irregularly lobulated (fig. 2).


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, 638–649

We administered cotrimoxazole (trimethoprim 160 mg +

sulphamethoxazole 800 mg) combined with intramuscular

streptomycin (750 mg) initially daily, and then on alternate

days. There was a perceptible reduction in the size of the swell-

ing with healing of sinuses 8 weeks later. In the course of follow-

up a report of confirmation of the identity of the isolate as

N. asteroides

and its

in vitro

drug sensitivity was received

from the Pasteur Institute, France. The isolate was found to be

sensitive to amikacin, tobramycin, cefotaxime, impenem and

cefamandole, but partially sensitive to erythromycin, amoxycillin

+ clavaulanic acid, cotrimoxazole and resistant to ampicillin,

ciprofloxacin and minocycline.

The man presented to us again with additional swellings at

other sites in July 2000. He was given 1 g of amikacin a day by

slow intravenous infusion for 15 days, followed by cefotaxime

for the same period without any appreciable change in the

status of disease. Subsequently, the treatment was changed to

oral cotrimoxazole (trimethoprim 160 mg + sulphamethoxazole

800 mg) daily associated with crystalline penicillin (500 mg)

intramuscularly four times a day for 6 weeks. This time healing

of the sinuses indicated the effectiveness of the treatment. Later

he was maintained on 1.5 g daily of both cotrimoxazole and

amoxycillin for 1 month. The disease was apparently cured in

the course of this treatment.

Actinomycetoma due to

N. brasiliensis

,

N. otitidiscaviarum

and

N. asteroides

have been reported in several parts of

India.

7–11

The largest series of mycetoma caused by

N. asteroides

in India was reported by Sanyal

et al

.;

3

the 18 cases described in

this report involved various body parts, including the foot. The

diagnosis in the current case was supported by the recovery of

N. asteroides

in culture and confirmed by demonstration of

homogeneous and/or rods of the fungus granules in tissue

sections.

N. asteroidesis

are divided into six types on the basis of

in vitro

antimicrobial sensitivity pattern. The present isolate was

assigned to type VI. In the earlier reports of nocardia mycetoma

and systemic nocardiosis from India, the isolates of

N. asteroides

were not assigned to any type. This report therefore is note-

worthy. Conservative treatment of actinomycetoma has proved

effective in the large majority of cases, and surgery is restricted

to patients with extensive lesions, only where a debulking oper-

ation can shorten the duration of the treatment.

12

Combination

therapy is recommended because of synergistic effects, and it

fig. 1 A swelling around the right ankle with multiple discharging sinuses. fig. 2 Non-specific granulomatous infiltrate around homogeneously staining

grains with radiating branching filaments at the periphery. Haematoxylin and

eosin, original magnification × 100.


642

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, 638–649

reduces the likelihood of resistance developing during the pro-

longed treatment.

12

The current case initially responded well to

treatment with cotrimoxazole and streptomycin, one of the rec-

ommended treatment modalities.

12

Recurrences of the swell-

ings may possibly be due to partial resistance of the isolate to the

preceding drugs. Surprisingly, the patient did not benefit much

from the therapy with amikacin and cefotaxime, to which the

isolate of

N. asteroides

was sensitive

in vitro

tests

.

The preceding

outcome was in striking contrast to the

in vitro

drug sensitivity

where the causative agent was only partially sensitive to cotri-

moxazole and sensitive to amikacin and cefotaxime, thus indi-

cating that

in vivo

drug sensitivity results of isolate(s) (

N.

asteroides

) may not always correlate well with

in vitro

results

.

HC

Gugnani,*†

VN

Sehgal,‡ VK

Singh,§ P

Boiron,¶ S

Kumar**

†

Department of Mycology Vallabhbhai Patel Chest Institute, University of

Delhi, Delhi 110 007, India,

‡

Dermato-Venereology (Skin/VD) Centre,

Sehgal Nursing Home, A/6, Panchwati, Delhi 110 033, India,

§

DST

Centre for the Study of Visceral Mechanisms, VPCI, University of Delhi,

Delhi, India,

¶

Laboratoire de Mycologie, Facult de Pharmacie, 8, Avenue

Rockfeller 69373 Lyon Cedex 08 France,

**

Department of Dermatology,

Safdarjung Hospital, New Delhi 110 029, India.

*

Corresponding author,

E-mail: [email protected]

References

1 Gugnani HC, Suseelan AV, Anikwe RM

et al.

Actinomycetoma in

Nigeria.

J Trop Med Hyg

1981;

84

: 259–253.

2 Sandhu DK, Mishra SK, Damaodaran VN

et al.

Mycetoma of the

knee due to

Nocardia caviae

.

Sabouraudia

1975;

13

: 170–171.

3 Sanyal M, Thammaya A, Basu N. Actinomycetoma caused by

Nocaridia asteroides

complex and closely related organisms.

Mykosen

1978;

21

: 109–121.

4 Thammaya A, Basu N, Sur-Roy Choudhary D

et al.

Actinomycetoma caused by

Nocardia caviae

in India.

Sabouraudia

1972; 10: 19–23.

5 Land GA. Identification of aerobic Actinomycetes. In: Isenberg HD,

editor. Clinical Microbiology Procedures Handbook.

American Society for Microbiology, Washington DC, 1996;

4.1.1–4.1.9.

6 Mishra SK, Gordon RE, Barnett DA. Identification of nocardiae and

streptomycetes of medical importance. J Clin Microbiol 1980; 11:

728–736.

7 Dasgupta LR, Sundarraj T, Agarwal SC. Actinomycetes from

mycetoma and other cases around Pondichery. Indian J Med Res

1974; 62: 765–775.

8 Desai SC, Pardanani YR, Kher YR et al. Therapeutic investigation

on actinomycetoma. Indian J Surg 1970; 32: 448–461.

9 Hazra B, Bandhopahdyay S, Saha SK et al. A study of mycetoma in

east, India. J Commun Dis 1998; 30: 7–11.

10 Joshi Kr Sangvi A, Vyas MCR et al. Etiology and diagnosis of

mycetoma in Rajasthan, India. Indian J Med Res 1987; 85:

694–698.

11 Klokke AH. Mycetoma in North India due to Nocardia crasiliensis.

Trop Geogr Med 1964; 2: 1701–1171.

12 Boiron P, Locci R, Goodfellow M et al. Nocardia, nocardiosis and

mycetoma. J Med Vet Mycol 1998; 36 (Suppl.): 26–37.16LetterLettersLetters

In vitro bactericidal effect of low-dose ultraviolet B in patients with acne

To the Editor

Beneficial effects of ultraviolet (UV) radiation on acne vulgaris

have been speculated but not generally accepted.1,2 The main

reason for that is the unsatisfactory documentation concerning

the risk/benefit ratio of UV radiation and acne treatment,

as some evidence exists that oxidative damage to the skin

on exposure to UV light may trigger comedogenesis and

colonization of propionibacteria.3 However, encouraging

results regarding in vitro inhibition of propionibacteria,

micrococcacea and staphylococci by UV radiation4 led to us

investigate the direct antibacterial effect of single exposure to

low-dose UVB of bacteria obtained from the pustules of acne

vulgaris subjects in vitro.

Fifty-four subjects (27 females and 27 males) with acne

vulgaris were enrolled in the study whose ages were between 15

and 29 years (mean ± SD = 19.44 ± 3.36 years). Samples were

obtained from the pustules of 51 subjects with acne vulgaris,

comprising 10 methicillin-sensitive Staphylococcus aureus and

50 Propionibacterium acnes samples. Four Petri dishes were

prepared from each bacterial sample, containing 1 × 105 bacteria/

mL, using chocolate agar and Schaedler agar, respectively. These

were exposed to 0, 50, 70 and 110 mJ/cm2 UVB and the

bacterial colonies were calculated after 24 h for S. aureus and

after 72 h for P. acnes samples. The UVB source was UV 8001 K

phototherapy cabin (Waldmann Lichttechnik, Schwenningen,

Germany) with fluorescent tubes emitting in the 285–350 nm

range with a peak at 315 nm. Statistical significance was

assessed by Wilcoxon matched-pairs signed-ranks test and

Mann–Whitney U-test.

Single exposure to UVB achieved a statistically significant

reduction in the number of colonies (mean ± SD) in each irra-

diated sample of (i) S. aureus, 0, 36.5 ± 30.6% (P = 0.005),

14.7 ± 21.1% (P = 0.005) and 3.1 ± 6.2% (P = 0.005), and

(ii) P. acnes, 0, 41.2 ± 24.1% (P < 0.0001), 20.7 ± 18.9%

(P < 0.0001) and 3.1 ± 6.5% (P < 0.0001), respectively (fig. 1).

When the findings for the two bacteria were compared, there

was no significant difference in the proportion of inhibition

of the colonies.

It is a common belief that sunlight improves acne.5 Although

the mechanism is unclear, immunosuppressive effects of UV

radiation may be involved.6 It is known that UVB induces pyri-

midine dimers on the same chain of DNA and such DNA

damage may have lethal effects to micro-organisms. We believe

that the beneficial effect of UV on acne may be due not only to


Letters 643

© 2002 European Academy of Dermatology and Venereology JEADV (2002) 16, 638–649

an immunosuppressive effect but also to a reduction of skin

surface bacteria. It has been pointed out that porphyrin photo-

reactions in P. acnes might be responsible for the photodestruc-

tion of this micro-organism after exposure to sunlight. Kjelds-

tad and Johnsson have shown that P. acnes is sensitive to

near-UV light, the sensitivity being highest at 320 nm and

related to the amount of porphyrin.2 Possible mechanisms

of inactivation involve the membrane damage in P. acnes and

other bacteria.

It has been claimed that suberythemal doses of UV radiation

was insufficient, and effective doses might be associated with an

increase in the hazards of UV light.7 As in standard protocol

phototherapy, the increments in doses of UV light are based

on the minimal erythematogenic dose of a particular subject;

therefore, the hazards of UV light may be inevitable, but if the

initial suberythematogenic dose is kept constant, the risk of

exacerbation of acne lesions may be avoided.

The results of this study confirm that irradiation by a single

suberythematogenic dose of UVB significantly reduces the

number of colonies of bacteria obtained from pustules of acne

vulgaris. It may be suggested that low-dose UVB may improve

the response to other treatment modalities in acne vulgaris.

However, the role of adjuvant low-dose phototherapy in

subjects presenting mild to severe forms of acne needs to be

investigated.

A Kalayciyan,†* O Oguz,† H Bahar,‡ MM Torun,‡ EH Aydemir†

Departments of †Dermatology and ‡Clinical Microbiology,

University of Istanbul, Cerrahpasa Medical School, Istanbul, Turkey.

*Corresponding author, Cerrahpasa Tip Fak, Dermatoloji ABD,

Kocamustafapasa, Istanbul, Turkey,

tel. +90 2125884800 (ext. 1547);

fax +90 2125870505;


References1 Lassus A, Salo O, Forstrom L et al. Treatment of acne with

selective-UV-phototherapy (SUP). An open trial. Dermatol

Monatsschr 1983; 169(6): 376–379.

2 Kjeldstad B, Johnsson A. An action spectrum for blue and

near UV inactivation of P. acnes; with emphasis on a possible

porphyrin photosensitization. Photochem Photobiol 1986; 43:

67–70.

3 Saint-Leger D, Bague A, Cohen E, Chivot M. A possible role for

squalene in the pathogenesis of acne. I. In vitro study of squalene

oxidation. Br J Dermatol 1986; 114: 535–542.

4 Jekler J, Berhbrant IM, Faergemann J, Larko O. The in vivo effect of

UVB radiation on skin bacteria in patients with atopic dermatitis.

Acta Derm Venereol (Stockh) 1992; 72: 33–36.

5 Gfesser M, Worret WI. Seasonal variations in the severity of acne

vulgaris. Int J Dermatol 1996; 35: 116–117.

6 Morison WL, Parrish JA, Block KJ. In vivo effect of UVB on

lymphocyte function. Br J Dermatol 1979; 101: 513–519.

7 Strauss SJ. Sebaceous glands. In: Fitzpatrick TB, Eisen AZ, Wollf K

et al., editors. Dermatology in General Medicine, 4th edn.

McGraw-Hill, New York, 1993: 709–726.16LetterLettersLetters

Cutaneous granulomas caused by corynebacterium minutissimum in an HIV-infected man

To the Editor

The term ‘coryneform bacteria’ is currently used to describe

Gram-positive, non-sporing, rod-shaped organisms. This hetero-

geneous group of bacteria is widely distributed in nature and

it includes Corynebacterium diphtheriae, the cutaneous aerobic

coryneforms (C. pyogenes, C. xerosis, C. hofannii, C. minutis-

simum and Brevibacterium epidermidis), as well as the anaerobic

Propionibacterium spp.1 Aerobic corynebacteria can be isolated

from normal human skin as saprophytic elements, but may

also be the cause of different skin pathologies.2 We describe

the case of an HIV-positive male with chronic granulomatous

lesions and subcutaneous abscesses on the legs from which

Corynebacterium minutissimum were isolated.

A 22-year-old man was referred for evaluation of 4-month-

old nodules on his legs; the four nodules were painful and one

had become suppurated, ulcerated and scarred. Past medical

history included parenteral heroin consumption. The man had

been seropositive for hepatitis B and C since 1997 and for HIV

since 1986. At the time of evaluation, his CD4+ T-cell count was

41/mL and HIV-1 RNA 102 000 copies/mL and he was under

treatment with didanosine (ddI), stavudine (dT4) and nelfinavir.

Physical examination revealed three indurated, hot, ery-

thematous, subcutaneous nodules on the front of the lower

extremities that were approximately 1 cm in diameter (fig. 1);

near one ankle there was an atrophic, depressed scarred plaque

(fig. 2). Skin biopsy specimens showed varying quantities of

neutrophils in the follicular infundibulum with suppuration.

The dermis showed rupture of the follicle at different levels of

the infundibulum and an abscess had formed. The inflamma-

tory cell infiltrate consisted of lymphocytes and histiocytes.

Cultures of biopsy material subjected to 24 h of incubation

on sheep blood agar grew non-haemolytic, non-lipophilic

fig. 1 The decrease in the number of S. aureus and P. acnes colonies

achieved with ultraviolet B irradiation.

JDV_653.fm 43 Friday, October 25, 2002 9:02 PM

644 Letters


smooth colonies, 1 mm in diameter, which showed a positive

catalase reaction and negative urea and motility reactions.

Carbohydrate fermentation studies revealed fermentation of

glucose, sucrose maltose and fructose, and lack of fermentation

of xylose, lactose and mannitol.

Treatment with 500 mg oral erythromycin (every 6 h for

10 days) achieved a clinical cure.

Since Propionibacterium acnes was first described by Unna in

1893 there has been considerable discussion in the literature

whether corynebacteria play a part in the pathogenesis of cutane-

ous lesions or whether it is only a saprophytic contaminant.3

However, it is difficult to assess the significance of the bacteria

in the pathogenesis of the affections reported.

In recent years, there have been increasing numbers of

reports of non-diphtheria corynebacteria as the cause of serious

opportunistic infection.4 This can be explained by: (i) the large

number of immunocompromised subjects whose diagnosis

and treatment have become continually more intensive and

invasive; (ii) the increased ability to identify these species in the

laboratory; and (iii) the recognition of the pathogenic potential

of coryneform bacteria.5

Cases in which corynebacteria are involved in the aetiology

of granulomatous skin lesions have been published infre-

quently.3,6–8 In particular, Binelli et al. published two cases of

granulomatous mastitis associated with corynebacteria in

which antibiotics and surgery led to cure.6 Nobre et al.

described a case of granulomatous lesions and subcutaneous

abscesses on the legs caused by antibiotic-resistant C. acnes.3 In

our case, however, the treatment administered gave favourable

results.

We think that, as in our case, immunosuppression due to HIV

favours infection by these saprophytic elements and also favours

the formation of granulomas; this is similar to experimental

findings with C. parvum, which has been used in the induction

of hepatic granulomas, whereby granulomas occurred even in

the absence of lymphocytes CD4 and CD8 in laboratory rats.9

In our case, we consider the aetiopathology of corynebacteria

to be proven because (i) they were isolated in skin cultures from

a biopsy performed with classic asepsia of the skin with iodized

alcohol, and (ii) clinical cure resulted from treatment with

erythromycin.

J Santos-Juanes,† C Galache,† A Martínez-Cordero,† JR Curto,†

MP Carrasco,‡ A Ribas,‡ J Sánchez del Río†

†Service of Dermatology II, ‡Service of Pathology II, Hospital Central de

Asturias, University of Oviedo, Asturias, Spain. *Corresponding author,

Servicio de Dermatología II, Hospital Central de Asturias, C/Julian

Clavería s/n, Oviedo, Asturias, Spain,

tel. +34985106100/ext. 36559

References1 Hay RJ, Adrians B. Bacterial infections. In: Rook, Wilkinson, Ebling

Textbook of Dermatology. Blackwell Science Ltd, Oxford, 1998:

1131–1136.

2 Braun-Falco O, Plewig G, Wolff HH, Winkelmann RK.

Dermatología. Springler-Velag Iberica, Barcelona, 1995.

3 Nobre G, Caldeira B. Chronic granulomatous infection of the legs

associated with Corynebacterium acnes. Br J Dermatol 1969; 81:

548–550.

4 Funke G, VonGraevenitz A, Claridge JE, Bernard KA. Clinical

microbiology of coryneform bacteria. Clin Microbiol Rev 1997; 10:

125–129.

5 Bandera A, Gori A, Rossi MC et al. A case of costocondral abscess due

to Corynebacterium minutissimun in an HIV-infected patient. J Infect

2000; 41: 103–105.

6 Binelli C, Lorimier G, Bertrand G et al. Mastites granulomateuses et

corynébactéries: a propos de deux observations. J Gynecol Obstet Biol

Reprod 1996; 25: 27–32.

7 Edmiston CE, Walker AP, Krepel CJ, Gohr C. The nonpuerperal

breast infection: aerobic and anaerobic microbial recovery

from acute and chronic disease. J Infect Dis 1990; 162:

695–699.

8 Berger SA, Gorea A, Stadler J et al. Recurrent breast abscesses caused

by Corynebacterium minutissimum. J Clin Microbiol 1984; 20:

1219–1220.

fig. 1 A hot, erythematous, subcutaneous nodule.

fig. 2 A depressed, scarred plaque.


Letters 645


9 Senaldi G, Shaklee CL, Mak TW, Ulich TR. Corynebacterium

parvum and Mycobacterium bovis bacillus calmette and Guerin-

induced granuloma formation in mice lacking CD4 and CD8.

Cell Immunol 1999; 193: 155–161.16LetterLettersLetters

Erythema multiforme associated with Trichophyton mentagrophytes infection

To the Editor

Erythema multiforme has a number of well known causes,

including infections (viral, bacterial, spirochaetal, rickettsial

and fungal), drugs, malignancy, connective tissue disorders and

idiopathic causes. Of the fungal causes, deep mycotic infections

such coccidioidomycosis and histoplasmosis are relatively

frequently associated with erythema multiforme, but super-

ficial mycoses are less frequently associated.

A 9-year-old boy presented with an acral, erythematous,

mildly pruritic, targetoid rash. Two weeks prior to this he had

noticed a pruritic, scaly patch on the dorsal aspect of his left

foot. This had spread between the fourth interdigital web space

to involve the adjacent plantar aspect of his foot. A week later he

then developed the more extensive lesions on his limbs. He was

otherwise well in himself and there was no preceding history of

coryzal symptoms, herpes simplex infection or drug ingestion.

On examination he had a well-circumscribed scaly patch on

the dorsal aspect of his left foot (fig. 1), which affected the

fourth web space, and also the plantar aspect of the foot. He also

had symmetrical erythematous macules, papules and plaques

some of which had a targetoid appearance (fig. 2) affecting his

hands, arms, legs and buttocks, including the palmar and

plantar aspects of his hands and feet. There was sparing of the

mucous membranes and he was apyrexial. Skin scrapings from

the scaly lesion on his foot showed fungal hyphae on micro-

scopy and grew Trichophyton mentagrophytes. Skin scrapings

from other lesions on his hands and body showed no evidence

of fungal infection. As the skin lesions were clinically typical of

erythema multiforme a skin biopsy was not undertaken and the

dermatophyte infection was treated with terbinafine cream.

The erythema multiforme resolved within 10 days as the der-

matophyte infection was brought under control and resolved

within 3 weeks.

Erythema multiforme affects all age groups but as many as

20% of cases are seen in children and adolescents. A recent

review1 of the causes of erythema multiforme in children over

a 20-year period revealed that 71% of cases were preceded by

infections. Of these Mycoplasma pneumoniae infection, acute

upper respiratory tract disease and herpes simplex infection

were the commonest causes. Superficial mycotic infection such

as T. mentagrophytes associated with erythema multiforme is

rare2,3 and probably represents an id reaction to the dermato-

phyte infection. Dermatophytide reactions typically take the

form of eczematous eruptions, although other reactions such as

erysipelas-like dermatitis, erythema annulare centrifugum, ery-

thema nodosum, pityriasis rosea-like reactions, urticaria and

erythroderma have been described.4

T. mentagrophytes is one of the two most common pathogens

in fungal foot infections and is probably the most common of

the acute infections, in contrast to T. rubrum which is more

often associated with chronic infection. This is because T. men-

tagrophytes induces a greater immune response and is therefore

more likely to produce a reaction such as erythema multiforme.

Although there is the possibility that the erythema multiforme

in this case was idiopathic, the close temporal relationship

between the dermatophyte infection and erythema multiforme

has led us to conclude that the erythema multiforme was related

to the T. mentagrophytes infection.

A Salim,* E Young

Department of Dermatology, Amersham Hospital, Whielden St,

Amersham, Bucks, HP7 OJD, UK.

*Corresponding author, Dermatology Department, Churchill Hospital,

Old Rd, Headington, OX3 7LJ, Oxford, UK,

tel. +1865 228272; fax +1865 228260;

E-mail: [email protected]. 1 Erythematous scaly eruption of Trichophyton mentagrophytes affect-

ing the right foot.

fig. 2 Erythema multiforme affecting the hands.


646 Letters


References1 Villiger RM, von Vigier RO, Ramelli GP et al. Precipitants in 42 cases

of erythema multiforme. Eur J Paedtr 1999; 158: 929–932.

2 Rahman SA, Setoyama M, Kawahira M, Tashiro M. Erythema multiforme

associated with superficial fungal disease. Cutis 1995; 55: 249–251.

3 Subban SA, Kamalam A, Thambiah AS. Erythema multiforme in

dermatophytosis. Mykosen 1979; 23(8): 452–455.

4 Burton JL, Holden CA. Eczema. In: Textbook of Dermatology

(Champion RH, Burton JL, Burns DA, Breathnach SM, eds),

6th edn, Vol. 1. Oxford: Blackwell Science Ltd, 1998:

637–638.16LetterLetterLetterxxxxxxxxx

Localized bullous pemphigoid as an unusual complication of radiation therapy

To the Editor

Here we present a patient who initially developed localized

bullous pemphigoid (BP) after radiation therapy for breast

carcinoma.

A 94-year-old woman was admitted in May 1999 with cancer

of her left breast (T3 N1 M1, stage IV), but surgical excision was

not performed because of her advanced age. The woman

received only primary radiation therapy with a total dose of

6000 cGy on her left breast and axillary region. Four months

after the radiation therapy, she developed bullous skin lesions

and eroded areas at the irradiation site of her left breast (fig. 1)

and 2 weeks later the eruption became generalized. Clinical

examination revealed multiple tense blisters filled with clear

fluid and several denuded lesions on the left breast, abdominal

region, arms and legs (fig. 2). Complete blood count, urinalysis,

erythrocyte sedimentation rate, liver function tests, renal

function tests, serum electrolytes, total proteins, and amino

acid profile were normal.

Histological examination revealed subepidermal blisters

with significant eosinophil infiltration in the dermis. Direct

immunofluorescent examination showed linear deposits of IgG

and C3 along the basement membrane zone.

Complete healing was obtained in 3 weeks with 60 mg/day

(1 mg/kg) oral prednisolone therapy.

BP is an unusual side-effect of radiation. To date some case

reports of radiation therapy-induced BP have been published,

including two subjects with initially generalized lesions1,2 and

several in whom the lesions were limited strictly to irradiated

areas.3–7

Our case involved a woman with metastatic breast carci-

noma who developed BP lesions that were initially limited to

irradiated areas and then became disseminated about 2 weeks

later. The diagnosis was confirmed by routine histological

examination and immunofluorescent study. Mastectomy had

not been performed because of the woman’s advanced age and

she received only radiation therapy. There was no other

explanation to account for the onset of the BP, such as

psoralen + ultraviolet A or ultraviolet B.5 To date only four

other cases have been reported in which the BP lesions were

limited to irradiated areas at the beginning then became

disseminated as in our patient.8–11 It has not yet been clarified

how radiation therapy induces BP lesions. The radiation therapy

may alter the normal structures of the basement membrane

zone resulting in the production of autoantibodies against a

new BP antigen.5,6 On the other hand, according to Bernhardt’s

hypothesis,3 these subjects may already have circulating

anti-basement membrane antibodies at a low titre and the

tissue damage caused by radiation therapy may enhance the

deposition of antibodies at the basement membrane zone. We

think that it is very important for dermatologists and radiation

oncologists to recognize promptly the onset of initially localized

radiation therapy-induced BP because it responds rapidly to

oral prednisolone therapy.

E Çalikoglu,†* R Anadolu,‡ C Erdem,‡ T Çalikoglu§

†Department of Dermatology, Fatih University Medical School, Ciftlik

cad. No: 57, 06510 Emek, Ankara, Turkey, ‡Department of Dermatology,

Ankara University Medical School, Ankara, Turkey, §Ankara Demetevle

Oncology Hospital, Ankara, Turkey. *Corresponding author,

fax: +90 3122213276; E-mail: [email protected]. 1 Eroded areas on the left breast.

fig. 2 Tense blisters with clear fluid on the left arm.


Letters 647


References1 Ive FA. Metastatic carcinoma of cervix with acanthosis nigricans,

bullous pemphigoid and hypertrophic pulmonary osteoarthropa-

thy. Proc R Soc Med 1963; 56: 910.

2 Abadir R. Pemphigoid, bronchial neoplasm and radiotherapy. Proc

R Soc Med 1967; 33: 1271.

3 Bernhardt M. Bullous pemphigoid after radiation therapy. J Am

Acad Dermatol 1989; 20: 14.

4 Sheerin N, Bourke JF, Holder J et al. Bullous pemphigoid

following radiotherapy. Clin Exp Dermatol 1995; 20: 80–82.

5 Cliff S, Harland C, Fallowfield ME, Mortimer PS. Localised bullous

pemphigoid following radiotherapy. Acta Derm Venereol (Stockh)

1997; 76: 330–331.

6 Ohata C, Shirabe H, Takagi K et al. Localized bullous pemphigoid

after radiation therapy: two cases. Acta Derm Venereol (Stockh)

1997; 77: 157.

7 Knoeel KA, Patterson JW, Gampper TJ, Hendrix JD. Localized

bullous pemphigoid following radiotherapy for breast carcinoma.

Arch Dermatol 1998; 134: 514–415.

8 Emery FW, Hare PJ, Abadir R. Pemphigoid, bronchial neoplasm

and radiotherapy. Proc R Soc Med 1967; 60: 1271–1272.

9 Furukowa F, Ozaki M, Imamura S, Hirose S. Bullous pemphigoid

associated with radiotherapy for oesophageal carcinoma.

Dermatologica 1981; 162: 451–455.

10 Duschet P, Schwartz T, Gschait F. Bullous pemphigoid

after radiation therapy. J Am Acad Dermatol 1988; 18: 441–

444.

11 Jappe U, Bonnekoh B, Gollnick H. Guess what! Initially localized

bullous pemphigoid at the irradiation site of breast carcinoma. Eur

J Dermatol 1999; 9(2): 139–141.16LetterLetterLetter

Death due to pulmonary tuberculosis in progressive systemic sclerosis

To the Editor

For 5 years a 58-year-old woman had presented with symptoms

of progressive systemic sclerosis (SSc), including heart, lung

and kidney involvement and doubtful involvement of the

oesophagus. The cutaneous involvement included tightening,

swelling of hands and feet with transition on arms and

legs, partly with fibrotic induration. Additionally we observed

a rigid face with telangiectases and Raynaud’s phenomenon.

Nailfold microscopy showed some loop dropout and

dilation.

Initial antinuclear antibodies were found in her serum at titre

of 1 : 20 000 using HEP-2 cells and anti-Pm-SCL antibody.

Myological studies (electromyogram, creatinine kinase) were

normal. There was only a discrete pulmonary fibrosis on the

chest X-ray and high-resolution computed tomography (CT).

Results of pulmonary function tests were within normal ranges.

Tuberculin allergy was not tested before.

The immunosuppressive therapy included methylpredniso-

lone (Urbasone®) 8–12 mg/d and azathioprine (Imurek®) 75–

100 mg/d for 4 years; later, mycophenolatmophetil (CellCept®)

2000 mg/d for 3 months was given. Some years ago penicillin G

and iloprost (Ilomedin®) infusions were used.

In January 2001 she began to deteriorate with increasing

fatigue, malaise and weight loss. Additionally, relapsing fever

up to 39 °C occurred. The following abnormal results in

laboratory tests were detected: raised potassium (5.4 mmol/L),

very high C reactive protein (136.6 mg/L) and low haemo-

globin (5.0 mmol/L). High-resolution CT scan of the thorax

only confirmed the presence of interstitial lung disease.

Furthermore, increasing reduction of vigilance presented

beyond somnolence, thus the patient was ventilated and

transferred to the intensive care unit. Pneumonia was detected

by bronchoscope and X-ray of the thorax. Microscopically,

bronchoalveolar lavage samples showed acid-fast bacilli and

the culture grew on Löwenstein–Jensen medium Mycobacte-

rium tuberculosis. A diagnosis of pulmonary tuberculosis

was confirmed. Despite tuberculostatic therapy (rifampicin,

isoniazid, streptomycin, ethambutol) the patient died of

septic shock.

Clinical features, chest X-rays, high-resolution CT and

echocardiogram findings were all typical of SSc and not

suggestive of tuberculosis.

M. tuberculosis infection in SSc is thought to be uncommon

because reported cases are rare: one report of a Japanese

Canadian patient,1 and two additional Russian case reports2,3

have been published. Cowie4 described a 40% incidence of prior

tuberculosis in black South African gold miners with SSc. He

concluded that there was an association between tuberculosis

and SSc independent of silica exposure or silicosis. It does

appear that the tuberculosis in these patients pre-dated

their SSc.4

SSc is accepted to be an autoimmune connective tissue

disease, although the precise mechanism of immune acti-

vation and perpetuation is yet unclear. Abnormalities of

both the cellular and humoral arms of the immune system

are described.5 Reduced numbers of circulating T lymphocytes

and decreased lymphocyte proliferation has been noted.6,7

It has been suggested that the subpopulation of T lym-

phocytes regulating cell-mediated immunity is selectively

reduced in SSc.8 Administration of mycophenolatmophetil,

azathioprine and methylprednisolone block the proliferation

of B and T cells in different ways and may be one of the major

factors predisposing to infection, such as tuberculosis or

aspergillosis.9 Protection from a M. tuberculosis infection

requires an intact cell-mediated immune response. Antibody

production is considerable, but this does not contribute to

protection.

Alternatively, tuberculosis could have triggered the

SSc. There is some evidence that microbial antigens are impor-

tant immunological triggers in several autoimmune disorders.


648 Letters


Possible mechanisms have been reviewed by Behar and

Porcelli.8 Structural similarity or molecular mimicry of

microbial antigens to host antigens may lead to an

immune response that becomes sustained. Infection due to

M. tuberculosis frequently occurs in latent forms. Dormant

viable bacilli may stimulate an immune response, and

reactivation usually creates a brisk response. High levels of

circulating antibodies to 65 kDa M. tuberculosis antigen, a

heat shock protein, was found in sera of patients with SSc

(47%).10

In conclusion, it is not clear if our patient presented a new

infection with M. tuberculosis or reactivation of a not yet detected

focus. Responsible to acquire the tuberculosis was – we

suppose – either the immunosuppressive therapy or the

immunodysfunction in the SSc patient.

B Manz,* F Noack-Wiemers, M Mittag, U-F Haustein, P Nenoff

Department of Dermatology, Universitiy Leipzig, Stephanstraße 11,

D-04103 Leipzig, Germany. *Corresponding author, tel. +49(0)341/

9718715; fax +341/9718609; E-mail: [email protected]

References1 Roddy J. Holby S, Seigel S. Scleroderma concurrent with culture

proven tuberculosis in a Japanese Canadian patient. J Reumatol

1996; 23: 2168–2170.

2 Tiukhtin NS, Berlova ZD. Exudative pleurisy with a tuberculous

etiology in a patient with systemic scleroderma [in Russian]. Probl

Tuberk 1979; 3: 68–70.

3 Kazak TI, Teriaeva MV, Turintsev BB, Davlinskaia OI. A case of

steroid tuberculosis in systemic scleroderma [in Russian]. Probl

Tuberk 1996; 2: 57–58.

4 Cowie RL. Silica-dust-exposed mine workers with scleroderma

(systemic sclerosis). Chest 1987; 92: 260–262.

5 Haustein UF, Anderegg U. Pathophysiology of scleroderma: an

update. J Eur Acad Dermatol Venereol 1998; 11: 1–8.

6 Whiteside TL, Kumagai Y, Roumm AD et al. Suppressor cell

function and T lymphocyte subpopulations in peripheral blood of

patients with progressive systemic sclerosis. Arthritis Rheum 1983;

26: 841–847.

7 Baron M, Keystone EC, Gladman DD et al. Lymphocyte

subpopulations and reactivity to mitogens in patients with

scleroderma. Clin Exp Immunol 1981; 46: 70–76.

8 Behar SM, Porcelli SA. Mechanisms of autoimmune disease

induction. The role of the immune response to microbial

pathogens. Arthritis Rheum 1995; 38: 458–476.

9 Nenoff P, Horn LC, Mierzwa M et al. Peracute disseminated

fatal Aspergillus fumigatus sepsis as a complication of

corticoid-treated systemic lupus erythematosus. Mycoses 1995;

38: 467–471.

10 Daniele MG, Candela M, Ricciatti AM et al. Antibodies to

mycobacterial 65 kDa heat shock protein in systemic sclerosis

(scleroderma). J Autoimmun 1992; 5: 443–452.

16LetterLettersLettersxxxxxxxControversies concerning the cure process in patients with pemphigus vulgaris

To the Editor

Pemphigus vulgaris (PV) is an autoimmune bullous skin disease

characterized by the presence of pathogenic autoantibodies in

the patient’s serum. PV requires long-term immunosuppressive

treatment. Clinical remission and negative results of immuno-

logical studies are well known criteria of definite cure.

Relapses of the disease in some patients after cessation of treat-

ment suggest the need for more sensitive tests to prove complete

cure. We performed examinations on the oesophageal mucous

membranes of PV patients who were in clinical remission and

the results of direct immunofluorescence (DIF) and indirect

immunofluorescence (IIF) tests were negative. We found that

pemphigus autoantibodies bound in intercellular spaces of the

oesophageal epithelium are observed for a longer time than in

the skin and circulation. David1 describes the relapse of the

disease after the discontinuation of treatment in one of eight

patients, perhaps due to low concentrations of pathogenic

autoantibodies in the serum that could not be detected by

routine methods.

In conclusion, we completely agree with the authors of the

letter that DIF examination of the skin and IIF test of the serum

in PV subjects in clinical remission are convenient. However,

our studies indicate that oesophageal examination gives better

and more highly sensitive results than examination of the skin.

Negative results of this examination is proof of complete cure.

None of our PV subjects with negative findings to DIF tests on

oesophageal membranes experienced relapse of the disease after

discontinuing treatment.2

JD Torzecka*

Department of Dermatology Medical University of Lodz, 94-017 Lodz,

Poland. *Correspondence address, fax +48 42 68 84 565;


References1 David M. A useful criterion of cure in pemphigus vulgaris. J Eur Acad

Dermatol Venereol 2000; 14: 327.

2 Torzecka JD, Waszczykowska E, Wozniacka A et al. Immunopath-

ological examination of oesophagus as a useful criterion of cure in

pemphigus vulgaris. J Eur Acad Dermatol Venereol 1999; 12: 115–118.16LetterLetterLetter

Lichen planopilaris and autoimmune thyroiditis

To the Editor

Lichen planus is a benign cutaneous and mucous disease

of unknown aetiology that may have an autoimmune patho-

genesis. Lichen planopilaris is a rare and distinctive variety


Letters 649


of lichen planus that selectively involves hair follicles and

causes scarring alopecia.1 At the onset there are violaceous

papules, erythema and desquamation. Later on follicular keratosis

appears in the absence of hair follicles. Histopathological

examination shows hyperkeratosis, acanthosis, increased

granular layer and degeneration of the basal cell layer.2 A band-

like lymphocytic cell infiltrate is present in the upper dermis

and the sebaceous glands are reduced in size or absent. Direct

immunofluorescent examination demonstrates cytoid bodies

and a linear deposit of fibrin along the dermoepidermal junction.

Lichen planus and its planopilaris variety are frequently

associated with autoimmune diseases, such as thymoma,

myasthenia gravis and alopecia. We report here the first case of

lichen planopilaris associated with autoimmune thyroiditis.

A 65-year-old woman presented to the Department of

Biomedical and Surgical Sciences (Section of Dermatology

and Venereology, Verona, Italy) with a defined patch of scalp

alopecia. Dermatological examination revealed a 5 × 4 cm,

oval-shaped, scarred plaque of hair loss on the vertex, with an

irregular border and some remaining tufts of hair. There were

erythematous to violaceous follicular and keratotic papules at

the periphery of the plaque. These manifestations had appeared

3 years before on the vertex and had later enlarged progres-

sively. The woman came to our department complaining of

intense itching that had started a few weeks before. There were

no other skin lesions, but we observed pitting on some of

the nails of the right hand. During the previous 2 years,

the patient had taken l-thyroxine for an autoimmune

hypothyroidism.

A scalp biopsy was taken and the examination by direct

immunofluorescence confirmed the diagnosis of lichen

planopilaris. The histopathological examination of the biopsy

material showed hyperkeratosis, hypergranulosis and a coarse

vacuolization of the basal cell layer. A dense perifollicular,

band-like, lymphocytic inflammatory cell infiltrate was observed.

The pilosebaceous apparatus was absent and replaced by dense,

eosinophilic, fibrous tissue.

Direct immunofluorescent examination showed cytoid

bodies of IgM along the basement membrane and a linear

deposit of fibrin along the dermoepidermal junction.

Blood tests confirmed only the presence of hypothyroidism

(FT4 = 19.8 ng/L, FT3 = 3.6 ng/L, thyroid-stimulating

hormone < 0.1 mUI/L) with positive antithyroid antibodies

(antithyroglobulin = 3940 U/mL, antimicrosomal = 1630 U/mL).

All other laboratory values were normal, including biochemical

analysis, antinuclear antibodies and antihepatitis C virus

antibodies.

Treatment with a medium potency topical corticosteroid

(prednicarbate) stopped both the itching and the acute phase of

the disease within 40 days. Over the next 2 years of follow up, no

relapse was observed.

Lichen planus and the planopilaris variety may be linked

to an alteration of immune tolerance. In lichen planus,

lymphocytes destroy keratinocytes, which show an unknown

antigen on their surface. The association of lichen planus

and viral hepatitis or certain drugs has been reported in the

literature, but it is not known why keratinocytes become a target.

One hypothesis is that viral proteins or drugs could connect to

the membrane of keratinocytes and work as haptens. In lichen

planus, cellular immunity is strongly involved with a typical

lymphocytic inflammatory cell infiltrate. Lichen planus is

frequently associated with autoimmune or immune-based dis-

eases, such as hepatitis, thymoma, myasthenia, Crohn’s disease,

ulcerative colitis and diabetes.3,4 The association between lichen

planus and other cutaneous autoimmune diseases, such as

dermatitis herpetiformis,5 vitiligo and alopecia areata6 has been

reported in the literature. As far as we know, the association

with autoimmune thyroiditis has never been described.

Thyroid diseases are frequently linked to other cutaneous

diseases, such as alopecia areata and vitiligo, which many invest-

igators consider as autoimmune diseases. Further studies are

required to verify the existence of pathogenetic mechanisms

common to lichen planopilaris and autoimmune thyroiditis.

Lichen planus is caused by cell-mediated immunity, while

thyroiditis is caused by antibody-mediated immunity. This

partial contradiction could be explained by the fact that

autoimmunity may be caused by lack of tolerance (and therefore

decreased T-cell activity) that could influence both T cells

(cell-mediated immunity) and B cells, resulting in increased

antibody production.

P Rosina, C Chieregato, M Magnanini, A Barba

Department of Biomedical and Surgical Sciences, Section of Dermatology

and Venereology, P.le Stefani 1, 37126 Verona, Italy.

*Corresponding author, tel. +39 45 8072547; fax +39 45 8300521;


References1 Mehregan DA, Van Hale HM, Muller SA. Lichen planus pilaris:

clinical and pathologic study of forty-five patients. J Am Acad

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Erythema multiforme associated with Trichophyton mentagrophytes infection

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