diagnosed as having IGDR induced by Chineseherbal medication and instructed not to take thesame medication. There was no recurrence withina 6-month follow-up period.

IGDR is a recently proposed drug associatedentity, first described in 1998.1 The most commonclinical pattern is asymptomatic infiltrative erythem-atous to violaceous plaques, mainly involving theintertriginous areas, medial thighs, and inner aspectsof the arms. Lesions are usually caused by intake ofdrug over a long period of time, ranging from 4weeks to 25 years (average, 5 years), and resolvingwithin 1 to 40 weeks (average, 8 weeks) after dis-continuation of the implicated drug(s). IGDR presentsvarious histologic features, such as an interstitialand palisaded array of histiocytic cell infiltrates with-out collagen necrobiosis, sometimes associated withinterface dermatitis.1-3 Histopathologic differ-ential diagnoses of IGDR include interstitial gran-ulomatous dermatitis with arthritis or plaques,interstitial granuloma annulare, palisaded neutro-philic granulomatous dermatitis, and methotrexate-induced popular eruption.3-4 The lack of completecollagen necrobiosis and leukocytoclastic vasculitis,together with a drug history, may be helpful differ-ential points in IGDR.2-3

The drug classes implicated in IGDR have in-cluded calcium channel blockers, angiotensin con-verting enzyme inhibitors, beta-blockers, diuretics,non-steroidal anti-inflammatory agents, lipid-lower-ing agents, antihistamines, anticonvulsants, anti-depressants, sennoside, and herbal medications.1-3,5

Herbal treatments are becoming increasinglypopular and are often used for dermatologic con-ditions such as atopic eczema.6 Potential cutaneousadverse effects of herbal medications include allergicskin reactions, Stevens-Johnson syndrome, photo-sensitization, pellagra, arsenic dermatoses, mercurypoisoning, and angioneurotic edema.6 Systemic sideeffects of Chinese herbal treatments for dermatologicconditions may include cardiomyopathy, hepatotox-icity and end-stage renal failure.6-7 IGDR should beadded to the list of adverse effects of Chinese herbalremedies, and dermatologists should be aware ofthese side effects of herbal treatments.

Hae-Woong Lee, MDWoo-Jin Yun, MDMi-Woo Lee, MDJee-Ho Choi, MD

Kee-Chan Moon, MDJai-Kyoung Koh, MD

Department of Dermatology, Asan Medical CenterCollege of Medicine, University of Ulsan

Seoul, Korea

Correspondence to: Mi-Woo Lee, MDDepartment of Dermatology, Asan Medical Center

College of Medicine, University of Ulsan388-1 Poongnap-dong, Songpa-gu

Seoul 138-736, Korea

E-mail: dermad@empal.com

REFERENCES

1. Magro CM, Crowson AN, Schapiro BL. The interstitial granulo-

matous drug reaction: a distinctive clinical and pathological

entity. J Cutan Pathol 1998;25:72-8.

2. Perrin C, Lacour JP, Castanet J, Michiels JF. Interstitial granulo-

matous drug reaction with a histological pattern of interstitial

granulomatous dermatitis. Am J Dermatopathol 2001;23:295-8.

3. Lee MW, Choi JH, Sung KJ, Moon KC, Koh JK. Interstitial and

granulomatous drug reaction presenting as erythema nodo-

sum-like lesions. Acta Derm Venereol 2002;82:473-4.

4. Tomasini C, Pippione M. Interstitial granulomatous dermatitis

with plaques. J Am Acad Dermatol 2002;46:892-9.

5. Fujita Y, Shimizu T, Shimizu H. A case of interstitial granuloma-

tous drug reaction due to sennoside. Br J Dermatol 2004;150:

1035-7.

6. Ernst E. Adverse effects of herbal drugs in dermatology. Br J

Dermatol 2000;143:923-9.

7. Ferguson JE, Chalmers RJG, Rowlands DJ. Reversible dilated

cardiomyopathy following treatment of atopic eczema with

Chinese herbal medicine. Br J Dermatol 1997;136:592-3.

doi:10.1016/j.jaad.2004.11.028

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Long-term complete remission of cutaneousmelanoma metastases in association witha folk remedy

To the Editor: We report a long-term completeremission of cutaneous melanoma metastases re-lated to the use of a folk treatment with the plantThymus vulgaris.

A 73-year-old white woman was referred to ourmelanoma unit in April 1999 with multiple bluish,cutaneous nodules over her left leg, which hadappeared during the previous 8 months (Fig 1, A).She reported that one year earlier a black skin lesionhad appeared over the same area of her leg, wherea splinter had been removed by another physicianwithout pathologic examination. She denied otherpathologic antecedents. Multiple cutaneous mela-noma metastatic nodules were diagnosed afterhistologic and immunohistologic examinations (Fig2, A and B). There were no lymph node or visceralmetastases on clinical, analytical, or staging ex-aminations (including body computed tomography,cerebral magnetic resonance imaging, and bonescintigraphy). The patient was staged at AJCC stageIII, but she refused the proposed treatment, which

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consisted of hyperthermic perfusion of the left legwith melfalan and interferon.

A few weeks later, a progressive disappearance ofall nodules was noted (Fig 1, B). Histologic ex-aminations confirmed the complete regression ofcutaneous metastases (Fig 2, C-F). The patient statedthat she had been using dried thyme (ground leavesand stems) for herbal tea and for topical applicationsin compresses over the lesions. No evidence ofdisease in this patient is apparent after 5 years offollow-up.

Spontaneous regression of cancer has been ob-served in different types of tumors. Malignantmelanoma comprises only 1.8% of all cancers, butit accounts for 11% of all reported cases of sponta-neous tumor regression. Partial regression of malig-nant melanoma is a well-known event and it is foundin 25% of primary melanomas.1,2 Although completespontaneous regression of primary melanoma is lessfrequent, between 5% and 10% of metastatic mela-nomas present with an unknown primary lesionor after a complete disappearance of the primarylesion.3 Thin primary melanomas with extensiveregression are at higher risk for development ofmetastases.4 Histopathologic features of regressedlesions include a normal-looking epidermis over-

Fig 1. A, Lower left extremity of the patient in April 1999with many cutaneous metastases. B, Complete responsewith the disappearance of all cutaneous lesions at March2002.

lying a fibroplastic area, with melanophagia, a densemononuclear cell inflammatory infiltrate, andneoangiogenesis.4

Spontaneous regression of metastatic melanomais extremely rare, and most cases occur in cutaneous,subcutaneous, and lymph node metastases,5 butregression of pulmonary6 and choroid7 cutaneousmelanoma metastases has also been observed.Before 1988, only 34 cases had been reported; todate, we have found about 20 more cases in theliterature.

Of the various mechanisms that have been pro-posed to explain the phenomenon of spontaneousregression, the immunological one remains the mostprobable.2 Recent documented cases of anti-tumoralactivity of a heterologous polyvalent melanomawhole cell vaccine have also provided indirectevidence of immune mediation in regression ofmelanoma.8 Pathak et al9 reported that spontaneousregression of Sinclair swine cutaneous melanoma isassociated with the loss of telomerase activity in theregressing tumors. It could be another mechanism

Fig 2. A, Hematoxylin and eosin staining of the cutaneousmetastasis with a malignant proliferation. B, Detail of themalignant cells a high magnification. C, Hematoxylin andeosin staining of the skin with a complete disappearanceof the tumor cells and the presence of extensive regressionand melanophagia. D, Detail of the melanophages in thedermis without the presence of tumour cells. E, Negativityof the HMB-45 staining. F, NKI staining. (A-D; Hematoxy-lin-eosin stain; original magnifications: A, 3100 B, 3400C, 3100 D, 3400 E, 3100 F, 3100.)

Vitiligo-like hypopigmentation associated withimiquimod treatment of genital warts

To the Editor: Pigmentary changes associated withimiquimod treatment have been reported and arelisted as possible side effects on the package insert.They have not, however, been well described inthe dermatologic literature. A 25-year-old man pre-sented in November 2001 with a history of condy-loma accuminata. His warts had been previouslytreated with liquid nitrogen without complication,but now he was presenting with a new wart. Thepatient was treatedwith electrodessication to a singlepenile lesion and was advised to use imiquimodtherapy for new lesions. Seven months later, hereturned with worsening penile warts and multipledepigmented patches on the scrotum ranging in sizefrom 3 mm to 2 cm (Fig 1). The patient reported thatthe involved areas had initially become very irritatedfrom the topical application of imiquimod 3 timesper week. He denied use of any other topicaltreatments. Imiquimod cream was discontinued andthe patient was prescribed podofilox 0.5% solution.The hypopigmented areas remained unchanged6 months later. The patient denied our request toobtain biopsies of the depigmented areas.

Through the Freedom of Information Act, weobtained US Food and Drug Administration recordsregarding adverse events associated with imiquimoduse from the drug’s approval in 1997 to November2003. Of the 1257 reports made, 68 (5.4%) were

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involved in spontaneous regression in human mel-anoma metastases.

We present a case of spontaneous regression ofmultiple cutaneous metastases of melanoma inassociation with the ingestion and topical applica-tion of T vulgaris (thyme) infusions. Thyme is a well-known medicinal herb, and the active component,thymol, has antimicrobial and antispasmodic prop-erties. The oil of T vulgaris has been reported to bean irritative agent in topical products and couldpotentially have a caustic effect on the skin at highconcentrations,10 but irritation was not present in thecurrent case.

Our case shows a chronological relationshipbetween T vulgaris and metastases regression, butthis association may be entirely coincidental, and wecannot confirm either a possible role of T vulgaris inthe induction of anti-tumoral autologous immuneresponse (producing an hypothetical haptenizationof tumoral antigens) or an intrinsic anti-tumoraleffect of Thymus extracts.

We thank Barbara J. Rutledge for her help in editing themanuscript.

Cristina Carrera, MDAmaia Mariscal, MDJosep Malvehy, MD

Susana Puig, MD, PhDMelanoma Unit, Dermatology Department

Hospital Clinic I Provincial BarcelonaIDIBAPS, Barcelona, Spain

Correspondence to: Susana Puig, MDDermatology Department

Hospital Clinic, Villarroel 17008036 Barcelona, Spain

E-mail: spuig@clinic.ub.es

Supported in part by grants 03/0019 from Fondo deInvestigaciones Sanitarias, V2003-REDC03/07, andgrant RO-1 CA 83115 (fund 538226 from National

Cancer Institute).

REFERENCES

1. Trau H, Kopf AW, Rigel DS, Levine J, Rogers G, Levenstein M,

et al. Regression in malignant melanoma. J Am Acad Dermatol

1983;8:363-8.

2. Saleh FH, Crotty KA, Hersey P, Menzies SW, Rahman W.

Autonomous histopathological regression of primary tumours

associated with specific immune responses to cancer antigens.

J Pathol 2003;200:383-95.

3. Menzies SW, McCarthy WH. Complete regression of primary

cutaneous malignant melanoma. Arch Surg 1997;132:553-6.

4. Guitart J, Lowe L, Piepkorn M, Prieto VG, Rabkin MS, Ronan SG,

et al. Histological characteristics of metastasizing thin mela-

nomas. A case-control study of 43 cases. Arch Dermatol 2002;

138:603-8.

5. King M, Spooner D, Rowlands C. Spontaneous regression of

metastatic malignant melanoma of the parotid gland and

neck lymph nodes: a case report and review of the literature.

Clin Oncol 2001;13:466-9.

6. Wang TS, Lowe L, Smith JW II, Francis IR, Sondak VK,

Dworzanian L, et al. Complete spontaneous regression of

pulmonary metastatic melanoma. Dermatol Surg 1998;24:

915-9.

7. Shields CL, Piccone MR, Fung KL, Shields JA. Spontaneous

regression of metastatic cutaneous melanoma to the choroid.

Retina 2002;22:806-8.

8. Vilella R, Benitez D, Mila J, Vilalta A, Rull R, Cuellar F, et al.

Treatment of patients with progressive unresectable meta-

static melanoma with a heterologous polyvalent melanoma

whole cell vaccine. Int J Cancer 2003;106:626-31.

9. Pathak S, Multani AS, McConkey DJ, Imam AS, Amoss MS Jr.

Spontaneous regression of cutaneous melanoma in Sinclair

swine is associated with defective telomerase activity and

extensive telomere erosion. Int J Oncol 2000;17:1219-24.

10. Barel AO, Manou I, Baudenelle C, Lambrecht R, Clarys P.

Assessment of the potential skin irritation caused by the

cosmetic use of essential oils from aromatic plants (Lamia-

ceae). Allergologie 1995;18:465-6.

doi:10.1016/j.jaad.2004.11.027