Interstitial granulomatous drug reaction to a Chinese herb extract

ARTICLE

ejd.2012.1700

Auteur(s) : Xu-Feng Du¹ docdxf@126.com, Xing-Ping Yin², Guo-Long Zhang¹, He-Jian Shi¹, Min-Hua Shao¹

¹ Department of Dermatology, Wuxi People's Hospital, 299 Qingyang Road, 214023Wuxi, China

² Department of Dermatology, Wuxi No.2 People's Hospital, Wuxi, China

Interstitial granulomatous drug reaction (IGDR) is a recently proposed drug-associated entity [1]. Many cases of IGDR have been reported in the literature, mostly induced by Western medicines, such as diuretics, antihistamines, sennoside, etc [1-4]. Lee et al reported a case of IGDR triggered by an unknown constituent of Chinese herbal medicine, in 2005 [5]. Panax notoginseng saponins (PNS) are the principal elements extracted from the traditional Chinese herb medicine Sanchi and have been widely used for cardiovascular and cerebrovascular diseases [6]. Here we described a case of IGDR to PNS.

A 73-year-old male presented to our department with asymptomatic, erythematous to carmine or violaceous macules, papules and plaques on his trunk and extremities for one month (figures 1A-B). Prior to developing the lesions, he had taken PNS soft capsules and aspirin pills for cerebral infarction, for about 2 months. Physical examination showed many slightly infiltrated and scaly macules, papules and plaques on the trunk and extremities, round to ovoid in shape. All the lesions gradually regressed two months later, after he stopped the PNS capsules. He had no arthritis, photosensitivity or any signs of collagen diseases. Complete blood cell count and urine analysis were within normal ranges and antinuclear antibody, rheumatoid factor, anti-ds-DNA, anti-Smith antibody were negative. No abnormality was noticed on the chest X-ray and the PPD test was negative. Two skin biopsies, taken respectively from fresh and old lesions, showed similar findings. A dense, diffuse, interstitial/perivascular, infiltrative mass, composed of lymphocytes, histiocytes, plasma cells and eosinophils, was found in the dermis, accompanied with sparse mucin deposition, atypical lymphocytes and erythrocyte extravasion in some areas. Leukocytoclasis and fibrinoid necrosis of the walls of small cutaneous blood vessels were not found. Granuloma, composed of epithelioid cells, mononuclear histiocytes, multinucleate giant cells and other inflammatory cells, was found and rosette-like collections of epithelioid cells surrounding thick collagen fibers were seen (figures 1C-E). Liquifaction degeneration of basal cells was observed in the fresh lesion. Four months later, the patient visited our department with almost identical eruptions again, after 5 days of only intravenous PNS injections. The eruptions gradually resolved 2 months after cessation of the medicine. IGDR was diagnosed according to the medical history and clinicopathological features and there was no recurrence in the 1-year follow-up.

IGDR was first described in 1998 [1]. Its mechanism is uncertain, it is assumed that inherent immune dysregulation may promote an exaggerated immune response to drugs in some cases [4]. Different clinical presentations, such as annular plaques, generalized erythematous macular and/or papular lesions, erythema nodosum-like lesions and different body sites, such as the back, trunk, extremities and palmoplantar areas, have been reported to date. Histopathologically, IGDR has various features [1-5], such as a diffuse interstitial/perivascular infiltration of lymphocytes and histiocytes in the dermis, sometimes associated with interstitial mucin deposition and interface dermatitis. Atypical lymphocytes may also be seen in some cases.

In the present case, the patient had identical lesions after using either PNS capsules orally or its injection intravenously and the eruptions gradually resolved after cessation of the drug. Absence of leukocytoclasis and fibrinoid necrosis of the walls of blood vessels excluded the diagnosis of drug-induced vasculitis. The medical history, clinical manifestations and pathological findings strongly suggested the diagnosis of IGDR to PNS.

PNS include more than 30 kinds of saponins. In our patient, the pathogenesis of IGDR to PNS is unclear, and we assume that an inherent immune dysregulation may have promoted an exaggerated and delayed immune reaction to any type(s) of PNS constituents.

Disclosure

Financial support : none. Conflict of interest : none

References

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2. Chen YC, Hsiao CH, Tsai TF. Interstitial granulomatous drug reaction presenting as erythroderma: remission after discontinuation of enalapril maleate. Br J Dermatol 2008; 158: 1143-5.

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6. Jia Y, Li ZY, Zhang HG, Li HB, Liu Y, Li XH. Panax notoginseng saponins decrease cholesterol ester via up-regulating ATP-binding cassette transporter A1 in foam cells. J Ethnopharmacol 2010; 28: 297-302.