Embed Size (px)
Citation preview
J AM ACAD DERMATOL
VOLUME 65, NUMBER 2Letters 453
Proposed mechanisms of sorafenib-induced handand foot syndrome and other cutaneous reactionsinclude dose-dependent direct toxicity and inhibi-tion of angiogenesis; however, the pathways respon-sible for sorafenib-induced PRP-like eruption areunknown and may be different. Sorafenib has nodirect activity on the epidermal growth factor recep-tor, but may block downstream pathways at the levelof RAF/MEK/ERK signaling, leading to alterations inkeratinocyte biology.1 The effect of sorafenib onkeratinocyte proliferation and differentiation is sup-ported by reports of sorafenib-induced KP-like erup-tion and eruptive keratoacanthomas and cysts.3,4
Although rare reports exist of malignancy-associated PRP in patients with various solid cancers,the acute onset of our patient’s rash after sorafenibinitiation suggest a drug-induced etiology, a conclu-sion that is consistent with sorafenib’s known effectson keratinocyte biology. Of note, exacerbation ofPRP has been reported with imiquimod and efalizu-mab therapy, but, to our knowledge, our case isapparently the first report of drug-induced PRP denovo.
Sorafenib-induced cutaneous side effects gener-ally occur after the third week of therapy and arereversible with dose reduction or discontinuation ofthe drug.2 For many patients, the focus of treatmentis to control the rash without discontinuing life-sustaining kinase-inhibitor therapy. In the case ofPRP, phototherapy, retinoids, or antietumor necrosisfactor agents may be effective treatment options.
Carlos Paz, MD, PhD, Christiane Querfeld, MD,PhD, and Christopher R. Shea, MD
Section of Dermatology, University of Chicago,Chicago, Illinois
Funding sources: None.
Conflicts of interest: None declared.
Correspondence to: Christopher R. Shea, MD, Dept.of Medicine, Section of Dermatology, Universityof Chicago, 5841 South Maryland Ave, MC 5067,Chicago, IL 60637
E-mail: [email protected]
REFERENCES
1. Wilhelm SM, Carter C, Tang L, Wilkie D, et al. BAY 43-9006 exhibits
broad spectrum oral antitumor activity and targets the RAF/MEK/
ERK pathway and receptor tyrosine kinases involved in tumor
progression and angiogenesis. Cancer Res 2004;64:7099-109.
2. Robert C, Mateus C, Spatz A, Wechsler J, Escudier B. Dermato-
logic symptoms associated with the multikinase inhibitor
sorafenib. J Am Acad Dermatol 2009;60:299-305.
3. Arnault JP, Wechsler J, Escudier B, Spatz A, Tomasic G, Sibaud V,
et al. Keratoacanthomas and squamous cell carcinomas in
patients receiving sorafenib. J Clin Oncol 2009;27:e59-61.
4. Kong HH, Turner ML. Array of cutaneous adverse effects
associated with sorafenib. J Am Acad Dermatol 2009;61:360-1.
doi:10.1016/j.jaad.2010.03.015
Treatment of shiitake dermatitis by balneoPUVA therapy
To the Editor: Shiitake (Lentinus edodes) dermatitis,also called toxicoderma, is a characteristic acute skinreaction that occurs after eating raw or half-cookedshiitake. Shiitake are semi-toxic mushrooms thatcontain the heat-labile toxin lentinan.1-3 Shiitakedermatitis mainly occurs in Japan, although thesemushrooms are also cultivated worldwide. Thusshiitake dermatitis has become more common inrecent years in Europe and the United States.Multiple cases have been published since the firstreport by Nakamura1 in 1977, but to date there is noeffective therapy.
A 44-year-old Caucasian man of ultraviolet (UV)skin type 2 presented with a 3-day history of anintensely itching flagellate dermatitis on his trunkand thighs that started 2 days after ingestion ofuncooked shiitake (Fig 1, A). He had taken nomedication and had no general or skin disease.Complete blood cell counts, including eosinophilsas well as hepatic and renal enzymes, provednormal. A skin biopsy specimen showed a slightlylichenoid eczematous dermatitis (Fig 2).
We treated the patient with a short-term balneo-PUVA therapy of two cycles with 0.5 mg methox-salen (8-methoxypsoralen [Ammoidin]) per literbath water and 0.1 J/cm2 UVA on days 5 and 6after ingestion of the mushrooms. Therapy in-duced an escalation of the itch within minutesafter UV light, resulting in an acute 2-hour itchingperiod. Thereafter, the pruritus abated markedly.Significant regression of the erythematous papuleswith complete clearance of the itch was seen 15hours after the first UV therapy. The second lighttherapy cycle on day 6 after shiitake ingestion didnot induce an itch-escalating effect. Four days aftertreatment, the skin lesions were completelyhealed. A second biopsy done 3 hours after thefirst treatment cycle showed no histologic differ-ence other than a marked reduction of epidermalLangerhans cells. We examined the following histo-logical stains: CD1a (reduction under therapy),CD207/Langerin (see Fig 2, reduction), CD3 (posi-tive, no difference), CD4 (see Fig 2, positive, nodifference), CD5 (positive, no difference), CD8 (seeFig 2, few cells positive, no difference), CD68 ( few
Fig 1. A, A 44-year-old male patient with characteristicflagellate dermatitis after ingestion of shiitake. B, Samepatient 4 days after balneo PUVA therapy.
Fig 2. Photomicrographs of biopsy specimens before and3 hours after first PUVA treatment. Hematoxylin-eosinstaining shows focally lichenoid and spongiotic, mainlyperivascular, superficial and deep dermatitis (A-D). Infil-trate consisted of mainly CD4-positive lymphocytes withsome CD8-positive cells (E-H). PUVA therapy inducedremarkable reduction of CD207 (langerin)epositive Lang-erhans cells (I-L). Scale bar: A, B, E-J ¼ 300 �m; C, D ¼ 75�m; K, L ¼ 150 �m.
J AM ACAD DERMATOL
AUGUST 2011454 Letters
cells positive, no difference), CD56 (negative), per-forin (negative),Giemsa stain ( fewperivascularmastcells and no remarkable eosinophils, no difference).Light test was done 10 days after treatment andshowed a slightly elevated photosensibility for UVA(40 J/cm2) and UVB (0.08 J/cm2).
In summary, we report instant alleviation ofshiitake dermatitis under PUVA therapy. Completeresolution of the condition was achieved within 4 to5 days after initiation of therapy while total time ofdisease from ingestion of shiitake was approxi-mately 10 days. There are no statistics on theaverage duration of shiitake dermatitis. In ourexperience and from case reports, most cases healwithin 2 to 3 weeks, but some cases need less than2 weeks to resolve on their own. Thus it remainsunclear whether PUVA therapy really shortened thetotal duration of the condition despite its initialsignificant effect in our patient. Two additionaldetails are of special interest in this case: theimmediate response to a low UVA dose and thetherapy-triggered initial brief aggravation of thedisease by massive itching. We hypothesize thatbalneo-PUVA therapy has not only acted by photo-immunological effects as in other diseases.4 In theliterature, increase of UVA, but not of UVB, photo-sensitivity by L edodes was reported.5 This mightsupport our findings of an early increase of itchingunder UVA light. Further studies are necessary to
prove the effect of UVA light on shiitake dermatitisand whether additional light sensitizing by psoralenis necessary.
Fig 1. Skin metastasis of choriocarcinoma.
J AM ACAD DERMATOL
VOLUME 65, NUMBER 2Letters 455
Nina Scheiba, MD,a Mindaugas Andrulis, MD,b
and Peter Helmbold, MDa
Department of Dermatology,a and the Institute ofPathology,b University of Heidelberg
Funding sources: None.
Conflicts of interest: None declared.
Correspondence to: Nina Scheiba, MD, Departmentof Dermatology, University of Heidelberg, Voß-strasse 2, 69115 Heidelberg, Germany
E-mail: [email protected]
REFERENCES
1. Nakamura T. Toxicoderma caused by shiitake (Lentinus edo-
des). Jpn J Clin Dermatol 1977;31:65-8.
2. Nakamura T. Shiitake (Lentinus edodes) dermatitis. Contact
Dermatitis 1992;72:65-70.
3. Mak RK, Wakelin SH. Shiitake dermatitis: the first case reported
from a European country. Br J Dermatol 2006;154:800-1.
4. Honig B, Morison WL, Karp D. Photochemotherapy beyond
psoriasis. J Am Acad Dermatol 1994;31:775-90.
5. Hanada K, Hashimoto I. Flagellate mushroom (Shiitake) derma-
titis and photosensitivity. Dermatology 1998;197:255-7.
doi:10.1016/j.jaad.2010.03.026
Mixed germ cell testicular tumor presenting asmetastatic cutaneous choriocarcinoma
To the Editor: A 38-year-old man, with polysubstanceabuse and hepatitis C infection, was admitted to thehospital with nausea and coffee-ground emesis. Hereported a 2-week history of two anterior chestnodules. Cutaneous examination revealed a 2.1- 31.7-cm firm, pink nodule with punctate hemorrhagiccrust and overlying pseudovesiculation on his rightupper lateral chest wall. Adjacent to this nodule wasa 0.5- 3 0.5-cm papule with similar features (Fig 1).Additionally, he was found to have a unilateralenlarged, firm testicular mass with greatest dimen-sion of 4.2 cm. The remainder of his physical exam-ination was unremarkable.
Laboratory tests showed a hemoglobin level of 4.9g/dL. The patient had a normal basic metabolicpanel, white blood cell and platelet count, as wellas liver and coagulation function tests. The b-humanchorionic gonadotropin (b-hCG) was remarkablyelevated at 55,540.0 mIU/mL. The erythrocyte sedi-mentation rate was 44 mm/h. Values for antinuclearantibodies, carcinoembryonic antigen, CA19-9,a-fetoprotein, prostate-specific antigen, and hapto-globin were all normal. His hepatitis C virus quan-titative viral load was 143,577 IU/mL.
Metastatic workup revealed retroperitoneal lym-phadenopathy, numerous bilateral lung masses, anda duodenal mass. Brain magnetic resonance imaging
showed multiple enhancing hemorrhagic masses.The cells were negative for placental alkaline phos-phatase, a marker for seminoma. Testicular orchiec-tomy revealed mixed germ cell tumor, with morethan 95% of choriocarcinoma and less than 5%seminoma.
Biopsy of the chest nodule revealed cutaneousmetastasis of choriocarcinoma. Within the dermiswas a dense, nodular, and interstitial infiltrate ofpoorly differentiated atypical and hyperchromaticcytotrophoblasts, admixed with several multinucle-ated hyperchromatic and atypical syncytiotropho-blasts (Fig 2, A and B). The b-hCG was diffuselypositive in the cytoplasm of syncytiotrophoblasticcells and placental alkaline phosphatase was nega-tive, thus confirming the diagnosis (Fig 2, C ).
In a mixed germ cell tumor, any admixture of apure germ cell tumor, such as choriocarcinoma, canexist. Choriocarcinoma can rarely be found in itspure form; however, it is most commonly seen as acomponent of a mixed germ cell tumor. In bothforms, choriocarcinoma has a biphasic pattern con-sisting of mononucleated cytotrophoblast cells thatlie in sheets to form villus-like structures and aplexiform arrangement of syncytiotrophoblast cellsthat secrete b-hCG.1
Choriocarcinoma has a marked tendency to me-tastasize early. Skin metastasis is rare with only 12cases previously reported and generally correlateswith a poor prognosis.2 Cosnow and Fretzin3 re-ported the first case in 1974, and a patient with thesefindings died 10 days after the initiation of chemo-therapy.4 A third case described a patient who died3 months after the appearance of his cutaneousmetastatic lesion to the upper back.5
First-line treatment of testicular choriocarcinoma ischemotherapy. Our patient was treated with rightradical orchiectomy and chemotherapy. He receivedwhole-brain radiation therapy and two cycles ofchemotherapy with etoposide and cisplatin. The pa-tient is currently alive 6 months after his presentation.
