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Acta Derm Venereol (Stockh) 1999; 79: 81^95

LETTERS TO THE EDITOR

Proximal White Subungual in the Immunocompetent Patient: Report of Two Cases and Review of the Literature

Sir, ture was performed and grew T. rubrum; a specimen sent for PAS Proximal white subungual onychomycosis (PWSO) is the rar- staining was positive for the presence of hyphae. The patient started est subtype of onychomycosis (1). In PWSO, the pulse therapy with 200 mg bid for 1 week each month. begins with fungal invasion of the stratum corneum of the At a return visit after two pulses of itraconazole, the patient was noted proximal nail fold, followed by infection of the deeper portions to have moderately improved. of the nail plate. This presentation of onychomycosis is most commonly caused by T. rubrum; other common causative agents include T. megninii, T. schoenleinii, T. tonsurans, T. DISCUSSION mentagrophytes,andE. £occosum (1, 2). The majority of initial cases of PWSO reported were patients The two cases we report, in addition to the others in the litera- with AIDS (1 ^ 3). In one study, 55 of 62 HIV-infected patients ture, indicate that there is a de¢nite subset of patients with with onychomycosis (83.7%) had PWSO (4). In more than PWSO who are immunocompetent. In patients with PWSO half of these patients (58%), T. rubrum was the etiologic with AIDS, toenail, rather than ¢ngernail, involvement has agent. PWSO has also been reported in patients with other been reported to be more common (1). In our cases, as well as immunode¢ciencies, including a renal transplant recipient on in some of the other immunocompetent patients, the ¢nger- immunosuppressive therapy (5), and a patient with systemic nails are prominent sites of involvement. This may be an erythematosus on systemic steroids (6). In addition, important factor in helping to di¡erentiate groups of patients Baran (7) described a case of proximal subungual with proximal subungual disease. onychomycosis as a manifestation of chronic mucocutaneous We can draw the following conclusions about PWSO. When . Recently, however, there have been several reports there is absence of , PWSO is usually caused by der- of immunocompetent patients developing PWSO (8 ^ 10). We matophytes and is seen mainly in immunocompromised now report two immunocompetent patients with proximal patients, especially when many nails are involved. If the patient white subungual disease, and review the other cases described, is not immunocompromised, a local cause of invasion, such as emphasizing that not all patients with this presentation are trauma, must be evaluated. PWSO with paronychia is usually a immunode¢cient. result of infection and occurs in both immunocompro- mised and immunocompetent patients.

CASE REPORTS

Case 1 A 47-year-old female physician without past medical history presented with a 2-month history of and edema around the proximal nail fold a¡ecting the left index ¢nger, associated with nail changes. She noted that she had been handling spoiled food 1 week before the start of her symptoms, but denied a preexisting wound or trauma. Prior to presentation, she was treated with mupurocin ointment and oral dicloxacillin without improvement. Examination revealed mild erythema of the proximal nail fold; the nail plate showed a white dis- coloration involving the proximal region. The patient was in good health and noted that, on a recent life insurance work-up, an HIV test was negative. A complete blood count was within normal limits. Culture and culture mount with lactophenol cotton blue showed ¢ndings consistent with species. She was treated with itraconazole 200 mg/daily for 4 weeks with clinical improvement.

Case 2 A 32-year-old Hispanic woman with a history of seizure disorder presented with complaints of nail changes over the previous 4 months. She had no prior history of problems with her nails and no other systemic complaints. She denied recent nail trauma or manicure. On physical examination, there was proximal , whitish discoloration, and subungual debris involving the thumbs, fourth ¢ngers, and great toes bilaterally, and the third left ¢nger (Fig. 1). A fungal culture was sent which grew Pseudomonas, but no fungi. An HIV test was performed, which was negative, and a chemistry panel and complete blood count, which were within normal limits. The patient returned for follow-up 3 weeks later. A repeat fungal cul- Fig. 1. Proximal subungual disease of the left third ¢ngernail.

# 1999 Scandinavian University Press. ISSN 0001-5555 Acta Derm Venereol (Stockh) 79 82 Letters to the Editor

REFERENCES sual manifestation of chronic mucocutaneous candidosis. Br J Der- matol 1997; 137: 286 ^ 288. 1. Elewski BE. Clinical pearl: proximal white subungual onychomy- 8. Piraccini BM, Morelli R, Stinchi C, Tosti A. Proximal subungual cosis in AIDS. J Am Acad Dermatol 1993; 29: 631 ^ 632. onychomycosis due to . Br J Dermatol 1996; 2. Silver-Lizama E, Logemann H. Proximal white subungual onycho- 134: 175 ^ 177. in AIDS. Int J Dermatol 1996; 35: 290 ^ 291. 9. Baran R, Tosti A, Piraccini BM. Uncommon clinical patterns of 3. Noppakun NM, Head EE. Proximal white subungual onychomy- Fusarium nail infection: report of three cases. Br J Dermatol cosis in a patient with acquired immune de¢ciency syndrome. Int J 1997; 136: 424 ^ 427. Dermatol 1986; 25: 586 ^ 587. 10. Dordrain-Bigot ML, Baran R, Baixench MT, Bazex J. Fusarium 4. Dompmartin D, Dompmartin A, Deluol AM, Grosshans E, onychomycosis. Ann Dermatol Venereol 1996; 123: 191 ^ 193. Coulaud JP. Onychomycosis and AIDS. Int J Dermatol 1990; 29: 337 ^ 339. Accepted May 29, 1998. 5. Lee MM, Diven D, Smith EB, Pupo RA. Onychomycosis. Arch Dermatol 1990; 126: 402. 6. Rongioletti F, Persi A, Tripodi S, Rebora A. Proximal white sub- Je¡rey M. Weinberg1, Evelyn K. Koestenblatt1, Philip C. Don1, Soren ungual onychomycosis: a sign of immunode¢ciency. J Am Acad M. White1, Mark N. Stein1 and Mahrukh Bamji2 Dermatol 1994; 30: 129 ^ 130. Departments of 1Dermatology and 2Pediatrics, New York Medical 7. Baran R. Proximal subungual candida onychomycosis. An unu- College-Metropolitan Hospital Center, New York, NY 10029, U.S.A.

Ring-induced Nail Pitting?

Sir, Nail pitting is a common feature of abnormal texture in nail plates. Here we describe a 24-year-old male Caucasian patient who noticed abnormalities on the surface of the nail plate of his right fourth ¢nger after wearing a new silver ring. Dermatolo- gical examination disclosed small, shallow pits in a mainly lin- ear, single row arrangement extending from the lunular to the free margin of the nail plate (Fig. 1). Apart from the cosmetic aspect, the pits caused no apparent inconvenience. Similar lesions had occurred earlier on his left fourth ¢nger after wearing a new gold ring, which disappeared after removal of the ring. The medical history of the patient and extended family was completely unremarkable.

Volker Grimm, Matthias MÎhrenschlager, Harald Bruckbauer, Lars D. KÎhler and Johannes Ring Department of and Biederstein, Technical University of Munich, Biedersteiner Str. 29, D-80802 Munich, Germany. Fig. 1. Small, shallow pits presenting in a mostly linear, single row arrangement extending from the lunular to the free margin of the nail plate of the right fourth ¢nger while wearing a ring.

Acta Derm Venereol (Stockh) 79 Letters to the Editor 83 Fox-Fordyce Disease: Two Cases in Patients with Turner Syndrome

Sir, Fox-Fordyce disease (FFD) occurs as a chronic, itchy, papular skin eruption principally located in the apocrine gland-bearing areas (1, 2). Although it usually appears in a symmetrical distribution on the axillae and pubic area, it can also occasionally a¡ect the labia, perineum, mammary areolae, presternal area, umbilicus and the medial aspect of the upper thighs. growth in the a¡ected regions is sparse or absent. Apocrine sweat is not produced at the ori¢ces of follicles of the a¡ected glands. Sometimes intense itching is present, apparently activated by intense sweating or by emo- tional excitation. More than 90% of reported cases have been observed in women between 13 and 35 years of age. The his- tologic picture is characterized by obstruction of the apocrine duct at its entrance into the follicular wall. The aims of this paper are to report two cases of FFD in two patients with Turner syndrome under treatment with growth hormone (GH) and to speculate as to whether these two conditions are correlated in any way.

CASE REPORTS

Case 1 A white 18-year-old girl was ¢rst seen in October 1992 for the evalua- tion of melanocytic naevi. The patient had been under observation since the age of 12 for short stature due to Turner syndrome. She had growth hormone (GH) de¢ciency and absence of ovaries; karyotype analysis was 45, X/46, Xi (Xq). The patient had been treated with GH 1 U/kg/week for 5 years in association with etinil-estradiol 100 Fig. 1. Fox-Fordyce disease in the axilla of patient 1. Note multiple, dis- ng/kg/day for the previous 3 years. In the previous 2 years, oxandro- crete, round, dome-shaped, follicular . Hair growth is sparse. lone 0.05 mg/kg/day had been added. At the time of our observation, the patient was still undergoing these 3 therapies and had a follicle-sti- area. Groin hair growth was normal and the patient did not complain mulating hormone value of 79.45 MIU/ml (normal value 3.7 ^ 10.5) of any symptoms. There was no family history of a similar disease, and and a luteinizing hormone value of 15.8 MIU/ml (normal value 1.6 ^ we decided not to treat the dermatosis. Histopathology showed mas- 10.0) as determined by £uoroimmunoassay kit (Eurogenetics). She was sive infundibular associated with lymphocytic exocyto- 142 cm tall. Besides numerous melanocytic naevi, she had ¢rm, £esh- sis and mild spongiosis. These pathological changes were consistent coloured, smooth, round, follicular papules located on both axillae. with FFD. These papules ranged between 1 ^ 3 mm in diameter; axillary hair growth was sparse (Fig. 1). The patient had complained of mild itching for several years. A diagnosis of FFD was made from the clinical pat- tern. There was no family history of the disease. Treatment with 0.1% DISCUSSION tretinoin cream for 4 weeks produced a marked reduction in pruritus, a Shelley & Levy (2) emphasize that the keratinous obstruction of mild regression of the papular lesions and an increase in hair growth. the upper limits of the apocrine duct is the earliest identi¢able Case 2 change in Fox-Fordyce disease. The disorder may be explained as a special form of apocrine sweat retention (apocrine ). A 16-year-old girl was referred to us in 1996 for pseudotinea amianta- cea of the scalp. She was a¡ected by Turner syndrome (karyotype 45 Recently, Ranaletta et al. (3), in an analysis of several speci- XO) and had been under observation since birth. mens, observed that some spongiotic vesicles are present not only Laboratory and instrumental investigations revealed a double renal in the follicular infundibula, but also in the eccrine gland acrosyr- pelvis, left polycystic kidney with functional hypertrophic right kidney, ingia. In addition, genetic in£uences probably play a role, since bicuspid aortic valve without functional failure and an increase in thyr- FFD has been reported in two members of the same family and oid hormone level with positive antitireoglobulin and antimicrosomial in male identical twins (4, 7). The most important skin manifesta- autoantibodies as a result of a previous autoimmune thyroiditis. Since tions of Turner syndrome are the tendency toward and 1990 she had been treated with GH 1U/kg/week. Her stature at obser- hypertrophic scar formation, increased number of melanocytic vation was below the third centile (145 cm), while her follicle stimulat- naevi, seborrhoeic , dry skin, anomalies of dermato- ing hormone value was 80.05 MIU/ml (normal value 3.7 ^ 10.5) and her glyphics of the ¢ngers and hypoplastic nails. Until now we have luteinizing hormone value was 18.8 MIU/ml (normal value 1.6 ^ 10.0) not found FFD in the group of cutaneous manifestations ofTurner as determined by £uoroimmunoassay kit (Eurogenetics). Since 1990 she had had elevated levels of follicle stimulating hormone. Physical syndrome in the literature, and we have never observed any other examination revealed a pseudotinea of the scalp, some melanocytic case of FFD associated with Turner syndrome or in therapy with naevi of the trunk and limbs as well as numerous erythematous, GH for short stature associated with idiopathic GH de¢cit. dome-shaped, shiny follicular papules, 2 mm in diameter, on the pubic The rarity of FFD in clinical practice could, in our opinion,

Acta Derm Venereol (Stockh) 79 84 Letters to the Editor be due to the fact that patients attribute little importance to 3. Ranaletta M, Rositto A, Drut R. Fox-Fordyce disease in two pre- light anomalies when asymptomatic, as in one of our cases. pubertal girls: histopathologic demonstration of eccrine This association between FFD and Turner syndrome may be involvement. Pediatr Dermatol 1996; 4: 294 ^ 297. casual, but it could also be hypothesized that the peculiar 4. Miller M, Harford RR, Yeager JK. Fox-Fordyce disease treated with topical clindamycin solution. Arch Dermatol 1995; 131: genetic condition of Turner syndrome and the particular hor- 1112 ^ 1113. monal alterations may make Turner patients favourable to 5. Giacobetti R, Caro WA, Roehigk HH. Fox-Fordyce disease. FFD. In fact, elevated follicle stimulating and luteinizing hor- Control with tretinoin cream. Arch Dermatol 1979; 115: 1365 ^ mone levels are frequently present in patients with Turner syn- 1366. drome because of their insu¤cient sexual hormone levels. 6. E¡endy I, Ossowski B, Happle R. Fox-Fordyce disease in a male Follicle-stimulating hormone has been considered an aetiologi- patient: response to oral treatment. Clin Exp Dermatol cal factor in FFD (5, 6). In addition, our two patients had been 1994; 19: 67 ^ 69. treated with growth hormone alone or in combination with 7. Graham JH, Shafer JC, Helwig EB. Fox-Fordyce disease in male sexual hormones. identical twins. Arch Dermatol 1960; 82: 104 ^ 113.

REFERENCES Accepted August 18, 1998. 1. Fox GH, Fordyce JA. Two cases of a rare papular disease a¡ecting the axillary region. J Cut Dis 1902; 20: 1 ^ 5. A. Patrizi1, C. Orlandi1, I. Neri1,P.A.Fanti1 and L. Mazzanti2 2. Shelley WB, Levy EJ. Apocrine sweat retention in man. II. Fox- 1Department of Clinical and Experimental Medicine, Division of Fordyce disease (apocrine miliaria). Arch Dermatol 1956; 73: Dermatology and 2First Pediatric Clinic, University of Bologna, via 38 ^ 49. Massarenti 1, I-40138 Bologna, Italy.

Successful Treatment of Generalized with Polyethylene Sheet Bath PUVA

Sir, PUVA therapy is known to be a successful mode of treatment for a number of in£ammatory dermatoses, including , , , and for generalized gran- uloma annulare (GA) (1). The usual oral administration of 8-methoxypsoralen (8-MOP) is associated with side-e¡ects on the internal organs and eyes (2). As an alternative, attention has recently been focused on the delivery of 8-MOP via the patient's bath water, since this treatment modality enhances the e¤cacy and safety of the standard PUVA technique (3, 4). The main drawback of bath PUVA is the high cost of liquid 8- MOP preparation. The use of a polyethylene sheet to reduce the volume of bath water can reduce the cost of the treatment by 90% (5). We describe a patient with generalized GA who was successfully treated with polyethylene sheet bath PUVA.

CASE REPORT A 50-year-old man had an asymptomatic papular eruption for 18 months. It began on the trunk and gradually spread to the extremities and became generalized. His general health was good and his personal and family history was unremarkable. Examination revealed numerous, arcuate red-purple papules varying from 3 mm to 7 mm in diameter. The papules were solitary or coalesced and distributed over the trunk and extremities (Fig. 1). The scalp, palmar and plantar sur- faces were not involved. He had a type III skin. The results of routine laboratory studies were within normal values (complete blood count, erythrocyte sedimentation rate, serum glucose, ions, liver enzymes, C-reactive protein, antistreptolysin-O-titre and urinalysis). Chest X-ray and abdominal ultrasound were also normal. Histological examination of an excised showed circumscribed necrobiotic foci of degenerated collagen ¢bres in the upper , surrounded by palisading in£ammatory cells. The in¢ltrate consisted Fig. 1. The patient's trunk showing generalized GA. Note the wide- mainly of histiocytes and a mixture of monocytes, foreign-body type spread arcuate red-purple papules varying from 3 mm to 7 mm in dia- giant cells, some lymphocytes and ¢broblasts. The diagnosis of general- meter.

Acta Derm Venereol (Stockh) 79 Letters to the Editor 85

number of therapeutic modalities have been used in the treat- ment of generalized GA, such as oral steroids, chloroquine, potassium iodide, niacinamide, cyclosporin, pentoxifylline, dapsone, and oral PUVA (1, 6). Since in the study of Kerker et al. (1) oral PUVA therapy of GA patients required long-term treatment and therefore carried the potential side- e¡ects of prolonged UVA exposure, such as non- skincancer,weusedbathPUVAtreatment.Inthetreatment of psoriasis, bath PUVA results in a signi¢cant reduction in the cumulative UVA dose, lowers the numbers of exposures and avoids short-, as well as long-term side-e¡ects on the inter- nal organs and eyes (3, 7, 8). Furthermore, bath PUVA elimi- nates the risk of intra-individual variations in 8-MOP plasma levels associated with the gastrointestinal absorption of oral 8- MOP (9). The main disadvantage of bath PUVA is that liquid 8-MOP preparation is expensive, but the use of the sheet bath method reduces the volume of bath water, and the total amount of 8-MOP per bath, thereby reducing the cost (5). Our patient had generalized GA, clinically and histologically, and we successfully used the sheet bath PUVA method, which indicates that it o¡ers a good treatment modality in this disorder.

REFERENCES 1. Kerker BJ, Huang CP, Morison WL. Photochemotherapy of gener- alized granuloma annulare. Arch Dermatol 1990; 126: 359 ^ 360. 2. Henseler T, Wol¡ K, HÎnigsmann H, Christophers E. Oral 8-meth- oxypsoralen photochemotherapy of psoriasis. The European PUVA study: a cooperative study among 18 European centers. Lancet 1981; 1:853^857. 3. Lowe NJ, Weingarten D, Bourget T, Moy LS. PUVA therapy for psoriasis: comparison of oral and bath-water delivery of 8-methox- Fig. 2. The patient0 s lesions resolved after bath PUVA treatment. ypsoralen. J Am Acad Dermatol 1986; 14: 754 ^ 760. 4. Calzavara-Pinton PG, Ortel B, HÎnigsmann H, Zane C, De Pan¢lis G. Safety and e¡ectiveness of an aggressive bath-PUVA regimen in ized GA was established on the basis of the characteristic clinical the treatment of psoriasis. Dermatology 1994; 189: 256 ^ 259. manifestation and . 5. Streit V, Wiedow O, Christophers E. Treatment of psoriasis with Polyethylene sheet bath PUVA therapy was initiated 4 times weekly. polyethylene sheet bath PUVA. J Am Acad Dermatol 1996; 35: A volume of 10 l psoralen (concentration 1 mg 8-MOP/l) was used in a 208 ^ 210. 20-min bath. UVA irradiation was performed immediately afterwards 6. Smith MD, Downie JB, DiCostanzo D. Granuloma annulare. Int J with a Waldmann 7001 (Waldmann Medical, Villingen-Schwenningen, Dermatol 1997; 36: 326 ^ 333. Germany), followed by a shower to remove the 8-MOP from the skin 7. Collins P, Rogers S. Bath-water delivery of 8-methoxypsoralen surface. The initial UVA dose was 0.5 J/cm2, the cumulative UVA dose therapy for psoriasis. Br J Dermatol 1992; 127: 392 ^ 395. was 35 J/cm2 and the number of treatments was 15. At the end of the 8. LÏftl M, Degitz K, Plewig G, RÎcken M. Psoralen bath plus UV-A treatment the patient's lesions resolved with only post-in£ammatory therapy. Possibilities and limitations. Arch Dermatol 1997; 133: remaining (Fig. 2). He has been symptom-free for 1597 ^ 1603. 6months. 9. Schafer-Korting M, Korting HC. Intraindividual variations of 8- methoxypsoralen plasma levels. Arch Dermatol Res 1982; 272: 1 ^ 7. DISCUSSION Accepted August 18, 1998. GA is a benign cutaneous disorder that has no proven aetiol- ogy or widely accepted theory of pathogenesis (6). The loca- Andrea Szegedi, Aè gnes Be¨ ga¨ ny and Ja¨ nos Hunyadi lized form of GA is usually self-limiting, but in generalized Department of Dermatology, University Medical School of Debrecen, GA spontaneous resolution is less common. A large and varied 4012 Nagyerdei kÎru¨ t 98, Hungary.

Acta Derm Venereol (Stockh) 79 86 Letters to the Editor Hypercalcaemia and Hypercalciuria after Topical Treatment of Psoriasis with Excessive Amounts of Calcipotriol

Sir, of 150 g calcipotriol per week for 10 months, or of 200 ^ The e¤cacy of the vitamin D analogue calcipotriol in the topi- 300 g and 360 g per week for two weeks (3). Interestingly, a rise cal treatment of chronic plaque psoriasis has been established in urine calcium excretion has also been demonstrated in in a large number of clinical trials (1, 2). Although calcipotriol patients using the drug at the maximum recommended rate of has 100 times less e¡ect on calcium homeostasis in vivo than 100 g/week (3). 1,25-dihydroxyvitamin D3, it may cause hypercalcaemia if used These reports taken together with our observation indicate to excess (2, 3). that even short-term topical application of calcipotriol is We report a patient su¡ering from generalized chronic capable of a¡ecting systemic calcium homeostasis. This e¡ect plaque psoriasis, in whom topical application of excessive of calcipotriol is presently thought to be mediated by an amounts of calcipotriol (Dovonex1)ointmentresultedinan enhancement of intestinal absorption of calcium and probably impressive improvement of his condition, but also in the of phosphate, which may result in hypercalcaemia and/or development of hypercalcaemia and hypercalciuria. hypercalciuria, hyperphosphataemia and hyperphosphaturia A 73-year-old man with a long history of chronic plaque and in suppression of parathyroid hormone and 1,25 dihy- psoriasis presented with a recent exacerbation of his disorder droxyvitamin D3 (3). In our case serum phosphate and para- refractory to therapy with dithranol and acitretin. The erythe- thyroid hormone levels were found to be within normal matosquamous plaques covered about 30% of his body surface. limits. However, since no baseline values of these parameters Subsequent to a thorough explanation of the possible adverse were available, it remains unknown whether therapy had e¡ects of calcipotriol, particularly after its excessive unlicensed exerted any modulatory e¡ect on them. usage, he was prescribed calcipotriol ointment (50 mg/g) and Although in all reported cases so far serum and urine was instructed to apply it topically twice daily according to calcium levels returned to normal after discontinuation of the manufacturer's guidelines. Pretreatment serum adjusted therapy, calcipotriol-induced hypercalcaemia and hyper- calcium levels were within normal limits (2.47 mmol/l; normal calciuria are adverse e¡ects of serious concern. It is, therefore, range 2.25 ^ 2.75 mmol/l). of essential importance to closely monitor the serum levels and Fifteen days later the patient was seen again in our out- the urine excretion rate of calcium in psoriatic patients, patient department and it was found that he had been applying particularly under long-term calcipotriol therapy, even when approximately 420 g of calcipotriol per week for 2 weeks. the manufacturer's guidelines are adhered. His skin lesions revealed an impressive improvement; the physical examination was otherwise normal. Serum-adjusted calcium levels were elevated (3.22 mmol/l) and hypercalciuria REFERENCES (11.05 mmol/24 h; normal range 2.5 ^ 7.5 mmol/l) was evident. 1. Ellis JP, Gri¤ths WAD, Klaber MR. Long-term treatment of Serum phosphate, magnesium, alkaline and acid phosphatase, chronic plaque psoriasis with calcipotriol ointment in patients liver and renal function tests showed no abnormalities. Serum unresponsive to short-contact dithranol. Eur J Clin Res 1995; 7: intact parathyroid hormone levels measured by immuno- 247^257. radiometric assay (CIS, Sur, Yvette, France) were within 2. Bourke JF, Iqbal SJ, Hutchinson PE. Vitamin D analogues in normal limits (23 pg/ml; normal values 10 ^ 65 pg/ml). psoriasis: e¡ects on systemic calcium homeostasis. Br J Dermatol Calcipotriol therapy was discontinued and 1 week later the 1996; 135: 347 ^ 354. values of both serum-adjusted calcium levels and 24-h urine 3. Bourke JF, Mumford R, Whittaker P, Iqbal SJ, Le Van LW, Trevellyan A, et al. The e¡ects of topical calcipotriol on systemic calcium excretion returned to normal. calcium homeostasis in patients with chronic plaque psoriasis. J There have been reports of hypercalcaemia in patients either Am Acad Dermatol 1997; 37: 929 ^ 934. with extensive psoriasis who used excessive amounts of calcipotriol or with unstable or pustular psoriasis who had Accepted June 2, 1998. applied approximately 100 g of the drug per week, but also in two cases with plaque psoriasis using calcipotriol within its S. Georgiou, MD and D. Tsambaos, MD licensed speci¢cation (2, 3). Additionally, hypercalciuria has Department of Dermatology, School of Medicine, University of Patras, been observed in psoriatic patients subsequent to topical use PO Box 1413, Rio ^ Patras 265 00, Greece.

Acta Derm Venereol (Stockh) 79 Letters to the Editor 87 Low Dose Cyclosporin A and Methotrexate in the Treatment of Psoriasis

Sir, to their regimen for 6 months (3). There was a signi¢cant clin- Cyclosporin A (CsA) and methotrexate are both e¡ective ical improvement on this therapeutic combination with no sig- drugs when used alone in the treatment of psoriasis. Few ni¢cant increase in adverse reactions. In a recent open study of reports in the literature have documented the combined 14 patients with refractory rheumatoid arthritis who received therapy of both drugs for this in£ammatory skin disorder. We both CsA (mean dose 2.5 ^ 3.9 mg/kg/day) and methotrexate describe a patient with severe psoriasis and psoriatic arthritis (10 ^ 15 mg/week) all clinical variables signi¢cantly improved who showed a clinically signi¢cant improvement on combined with this treatment regimen over a 6-month period (4). In addi- therapy with low dose CsA and regular dose methotrexate. tion, the combination treatment showed no greater toxicity than can be expected on treatment with single agents over this period. Tugwell et al. compared combination therapy with CsA CASE REPORT (2.5 ^ 5 mg/kg/day) and methotrexate (at the maximal toler- A 37-year-old male pharmacist presented with longstanding psoriasis ated dose) to methotrexate and placebo in 148patients with of 16 years' duration and arthritis a¡ecting mainly the axial skeleton severe rheumatoid arthritis in a large double-blind 6-month and peripheral joints. On initial presentation the patient had severe study (5). The study concluded that patients who had only par- psoriasis (PASI~15) and psoriatic arthritis, the latter treated with tial responses to methotrexate had clinically important methotrexate. Methotrexate however had no therapeutic e¡ect on the improvement after combination therapy with CsA and metho- skin manifestations of his psoriasis. Subsequently methotrexate was trexate. In addition, the side-e¡ects were not signi¢cantly weaned and CsA (3 mg/kg/day) was started for his psoriasis. Over increased. the next several months there was marked clinical improvement of his From the evidence available in the current literature it psoriasis (PASI~3.7) but CsA failed to control his associated arthritis. Therefore a combination of CsA and methotrexate was begun. The appears that potential side-e¡ects are not substantially patient has been maintained on low dose CsA (mean 2 mg/kg/day) in increased when CsA and methotrexate are used in combina- addition to intramuscular methotrexate (7.5 ^ 20 mg/week) for almost tion, as is illustrated in our case. Minimal side-e¡ects were 24 months (although a CsA-free period of 3 months occurred after 12 observed with low dose CsA and conventional dose methotrex- months of combined therapy at the request of the patient). This drug ate treatment for psoriasis over a period of 24 months. The combination has achieved a relatively stable control of his skin and lower doses of CsA administered in our patient and in the arthritic symptoms. Serum creatinine did not rise above 30% of base- above studies probably reduced the side-e¡ects of combined line and the patient experienced no other documented side-e¡ects CsA and regular dose methotrexate therapy. Both serum crea- whilst on this combined oral therapy. tinine and folate should be monitored when this combination is used. Future large-scale studies may be warranted to assess the DISCUSSION safety of this combined therapy in the treatment of psoriasis and associated psoriatic arthritis. This case is unusual in that methotrexate was ine¡ective in controlling the psoriatic skin manifestations, while CsA had no therapeutic e¡ect on the arthritic symptoms. However, REFERENCES when both drugs were used in a combination of low dose CsA and regular dose methotrexate, good therapeutic control of 1. Mazzanti G, Coloni L, De Sabbata G, Paladini G. Methotrexate both skin and joint symptoms was achieved. Few reports in and cyclosporin combined therapy in severe psoriatic arthritis. A the current literature document the combined use of CsA with pilot study. Acta Derm Venereol (Stockh) 1994; Suppl. 186: 116 ^ 117. other anti-psoriatic treatments. Mazzanti et al. reported the 2. Korstanje MJ, van Breda Vriesman CJP, van de Staak WJBM. e¡ectiveness of combination low dose CsA and methotrexate Cyclosporin and methotrexate: a dangerous combination. J Am in the treatment of 8 patients with severe psoriatic arthritis Acad Dermatol 1990; 23: 320 ^ 321. (1). The side-e¡ects documented were only a mild increase in 3. Bensen W, Tugwell P, Roberts RM, et al. Combination therapy of serum creatinine in one patient and reversible hypertension in cyclosporin with methotrexate and gold in rheumatoid arthritis (2 another. Korstanje et al. highlighted the increase in risk of ser- pilot studies). J Rheumatol 1994; 21: 2034 ^ 2038. ious side-e¡ects when CsA and methotrexate were used conco- 4. Sala¤ F, Carotti M, Cervini C. Combination therapy of cyclosporin mitantly in psoriasis, mainly that each drug decreased A with methotrexate or hydroxychloroquine in refractory rheuma- elimination of the other, leading to an increase in blood levels toid arthritis. Scand J Rheumatol 1996; 25: 16 ^ 23. of each drug. The study also reported increases in serum crea- 5. Tugwell P, Pincus T, Yocum D, et al. Combination therapy with cyclosporin and methotrexate in severe rheumatoid arthritis. N tinine as well as liver transaminases (2). However, their study Engl J Med 1995; 333: 137 ^ 141. comprised only 4 patients and since then considerably more data have been generated on the use of this drug combination, Accepted July 15, 1998. speci¢cally in the area of rheumatology. Bensen et al. reported 20 patients with rheumatoid arthritis Kenneth C. Wong and Katherine Georgouras who had a partial response to conventional dose oral metho- Dermatology Centre, Liverpool Hospital, 45 ^ 47 Goulburn Street, trexate and then had CsA (mean dose 2.5 mg/kg/day) added Liverpool, New South Wales, Australia 2071.

Acta Derm Venereol (Stockh) 79 88 Letters to the Editor Epidermal Inclusion with Melanoma-like Melanophagic Proliferation

Sir, by similar oval-to-fusiform pigmented cells. The giant cells also showed In a review of 128 cutaneous epithelial in the past year, we melanin within the cytoplasm. A few of the sections showed a tract of found 6 cysts that were pigmented, of which 3 were also asso- communication lined by granulomatous tissue between the two ciated with a granulomatous reaction. Among these, there was cavities. an unusual specimen which merits detailed description. DISCUSSION CASE REPORT The present case showed features of a ruptured pigmented A 26-year-old male had had a painless right gluteal swelling for the epidermal cyst. The unusual feature is its association with an past 10 years. It measured 5 cm64 cm and was soft and non-£uctuant. exuberant melanophagic proliferation, which has not been The swelling was excised. previously reported. The cells were plump oval-to-fusiform The surgical specimen measured 4 cm63cm63 cm and appeared as and markedly pigmented. The nuclei showed no atypia. Our an irregular mass of adipose tissue. The cut surface revealed a bilocular initial impression was either a naevus or melanoma in associa- cystic lesion (Fig. 1). The larger cyst (A) measured 2 cm in diameter and tion with an epidermal cyst. Immunohistochemical stains had a thick ¢brous wall with a smooth, pearly white inner lining. This revealed S100 and HMB to be negative, leading to the inference showed a focal black pigmented area of 0.660.4 cm. The smaller that these were melanophages. We presume that chronic cavity, (B), was collapsed, irregular and completely surrounded by irritation of this subcutaneous epidermal cyst was responsible black tissue. Microscopically, the larger cyst was lined by keratinizing strati¢ed for the rupture and increased production of melanin by squamous epithelium with marked hyperpigmentation of the melanocytes, which provoked a granulomatous reaction and keratinocytes. Melanocytes arranged in the basal layer showed en- melanophagic proliferation. Another unusual feature was that largement, but no nuclear atypia. The pigment also stained the luminal the rupture of the cyst led to formation of an irregular cavity, keratin £akes. The focal pigmented area in the wall included a collec- giving this lesion a ``double-deckered'' appearance. tion of heavily pigmented cells, obscuring the cytologic morphology (Fig. 2). The pigment was identi¢ed as melanin by the bleaching reac- tion. The cells were seen to be oval- to spindle-shaped, with moderate Accepted June 25, 1998. cytoplasm and round-to-oval vesicular nuclei. Immunohistochemistry showed no evidence of S100 or HMB 45 positivity in these cells, indicating that they were melanophages. Pradeep Vaideeswar, Daksha P. Prabhat and Ammu Sivaraman The smaller cavity, which lacked an epithelial lining, was lined by a Department of Pathology, Seth G. S. Medical College and K. E. M. very prominent foreign body giant cell reaction. This was surrounded Medical Hospital, Parel, Mumbai 400 012, India.

Fig. 1. Bilocular lesion showing larger cyst (A) with a pigmented area Fig. 2. Pigmented area in cyst wall composed of heavily pigmented (arrow) and smaller cavity (B) surrounded by black tissue. oval-to-fusiform cells; similar cells also surrounded the cavity.

Acta Derm Venereol (Stockh) 79 Letters to the Editor 89

Histamine Intolerance Imitated a Fish Allergy Table I. Foods high in histamine, and drugs that inhibit intesti- nal diamine oxidase

Sir, Histamine (mg/kg) Histamine plays an important role as a mediator in allergic and pseudoallergic reactions. The biological e¡ects of hista- Foods mine under physiological and pathophysiological conditions Fish are well known and are mediated by speci¢c H and H sardines 1500 1 2 tuna 13 000 max. receptors. Furthermore, histamine is a widely distributed bio- anchovy 176 genic amine, found in many foods (1). The level of histamine Cheese in the blood after eating histamine-rich foods depends on its Emmenthaler 555 passage through enterocytes. Diamine oxidase, located in the Gouda 180 enterocyte cytoplasm, is thought to be important in inactivat- Tilsiter 60 ing histamine before it enters the blood system. Previous Sausage observations led to the hypothesis that a decrease in the salami 279 activity of diamine oxidase may be responsible for the Vegetable increase in blood level of histamine that precedes allergic sauerkraut 200 reactions (2). tomatoes 22 Wine/beer 13 In this case we report that a high level of histamine in tuna Drugs was responsible for an anaphylactoid reaction caused by hista- Imipenem Clavulanic acid mine intolerance. Dobutamine Dihydralazine Pancuronium Chloroquin Pentamidine Cycloserine CASE REPORT Salazosulfapyridine Acetylcysteine Verapamil Metoclopramide A 44-year-old woman su¡ered an anaphylactoid reaction (grade III) (3) Isoniazid Cefuroxime 15 min after eating a ¢sh dish consisting of salmon, tuna, red snapper and shrimps. The patient required emergency treatment with epinephrine, high-dose and antihistamines. After exclusion of other causes of incompatibility she was sent to us for allergy diagnosis. REFERENCES All serum laboratory data were normal. No speci¢c IgE antibodies 1. Diel E, Bayas N, Stibbe A, et al. Histamine containing food: estab- against ¢sh or other food were found. In PRICK tests with seasonal lishment of a German food intolerance databank (NFID). In£amm and perennial aeroallergens, fungi and ¢sh and other foods no type I Res 1997; 46 (Suppl. 1): 87 ^ 88. sensitization was detected. In oral provocation with 1 ^ 20 g ¢sh (sal- 2. Sattler J, Hafner D, Klotter HJ, et al. Food-induced histaminosis as mon, shrimps and tuna) no reaction was observed. an epidemiological problem: plasma histamine elevation and haemo- An oral provocation test with histamine was then performed. The dynamic alterations after oral histamine administration and blockade patient developed diarrhoea 30 min after ingesting 60 mg of histamine. of diamine oxidase (DAO). Agents Agens 1988; 23: 361 ^ 365. The serum level of histamine was elevated six times (121.9 ^ 745.7 mg/l) 3. Ring J, MeÞmer K. Incidence and severity of anaphylactoid reac- compared with base level. We therefore made the diagnosis of hista- tions to colloid volume substitutes. Lancet 1977; 1: 466 ^ 548. mine intolerance. 4. O'Neil C, Helbing AA, Lehrer SB. Allergic reactions to ¢sh. Clin Rev Allergy 1993; 11: 183 ^ 200. 5. Sanchez-Guerrero IM, Vidal JB, Escudero AI. Scombroid ¢sh poi- DISCUSSION soning: a potentially life-threatening allergic-like reaction. J Allergy There are many published reports of as a speci¢c Clin Immunol 1997; 100: 433 ^ 434. 6. Wantke F, GÎtz M, Jarisch R. Die histaminfreie DiÌt. Hautarzt allergic reaction to ¢sh, shrimps or other types of seafood (4, 1993; 44: 512 ^ 516. 5). The present case, however, shows that histamine intoler- ance should be included in the di¡erential diagnosis of ana- Accepted July 6, 1998. phylaxis after eating ¢sh. After a diagnosis of histamine intolerance, patients must be advised to avoid histamine-rich M. Thewes, J. Rakoski and and J. Ring food, and drugs which may block intestinal diamine oxidase Department of Dermatology and Allergy, Technical University of (Table I) (6). Munich, Biedersteiner Str. 29, D-80802 Munich, Germany.

Acta Derm Venereol (Stockh) 79 90 Letters to the Editor Zosteriform Cutaneous Metastases arising from Adenocarcinoma of the Colon: Diagnostic Smear Cytology from Cutaneous Lesions

Sir, were grouped, in¢ltrated, erythematous and crusted papules, or trans- Cutaneous metastases arising from internal malignancy are lucent (Fig. 1). There was marked non-pitting oedema on his left leg. uncommon, and a zosteriform pattern is very rare. We report Material from the base of a translucent papule, obtained by curettage a case of colonic adenocarcinoma metastasizing to the left with a scalpel, was smeared onto a glass slide, and stained with Giem- lower extremity in a zosteriform pattern. No herpetic cyto- sa's stain. Although the smear showed no herpetic balloon cells, atypi- cal cells occurred in cohesive groupings or in a papillary structure. pathic changes were noted, and cohesive malignant cells in Those cells had round, ovoid nuclei and small to moderate amounts the papulo-vesicular lesions were observed on a Tzanck smear. of clear cytoplasm (Fig. 2a). The cytoplasm in those cells stained posi- Mucin production from tumour cells is the most likely source tive for carcinoembryonic antigen (CEA). Well-di¡erentiated meta- of the vesicular appearance. static adenocarcinoma was suspected. Laboratory data revealed a normal complete blood count (cbc). The chemistry pro¢le was found to be within normal limits. Serum CEA level and CA. 19-9 level were CASE REPORT 98 ng/ml (normal; 0 ^ 5), and 57 U/ml (normal; 0 ^ 30), respectively. Computed tomography (CT) of the abdomen showed marked lympha- In December 1990 a 65-year-old man underwent a palliative colostomy denopathy in the left inguinal and para-aortic lymph nodes. for sigmoid colon cancer with spreading to the peritoneum. In January Histological examination of a skin biopsy showed numerous tumour 1995 he noticed swelling of the left thigh, and he received local radio- nests in the papillary and reticular dermis (Fig. 2b). The lumina of these therapy and chemotherapy. The patient was referred to our dermatol- granular con¢gurations contained necrotic debris. Mucin in the colum- ogy clinic 1 month later for evaluation of skin lesions on his left leg. In nar tumour cells and the stroma stained with colloidal iron stain. July 1995, he noticed painless, erythematous in£ammatory papules and Furthermore, poorly di¡erentiated cells with pleomorphic nuclei in¢l- nodules. Because of the dermatomal distribution of the lesions, the trated among the collagen bundles in Indian ¢le formation. No dilated diagnosis was thought to be herpes zoster. He was started on oral dermal lymphatics with tumour cells in their lumen were observed. acyclovir but did not improve. Immunoperoxidase stains for CEA and CA 19-9 gave positive results. Examination revealed several ¢rm papules and nodules in an L-1 to The morphological and immunohistological ¢ndings were consistent L-3 dermatomal distribution on his left thigh. The numerous lesions with metastatic adenocarcinoma of the colon. The patient died 5 months later. An autopsy was not performed.

DISCUSSION Patients with colonic adenocarcinoma have been shown to reveal metastases to the skin in 4.4% of all cases (1). Certain internal malignancies appear to metastasize to speci¢c sites. Because the malignant cell may spread by direct extension from the underlying tumour or dissemination to local sites through the lymphatics, the abdominal wall is the most fre- quent site of colonic metastases. A review of the literature has not shown any cases of cutaneous metastases from colonic ade-

Fig. 2. Cytological presentation from a papule on the cutaneous lesions revealing (a) well-di¡erentiated adenocarcinoma and (b) histo- pathology showing a proliferation of well-di¡erentiated adenocarci- Fig. 1. Cutaneous nodules and vesiculo-papules on the left thigh in noma cells forming solid nests of varying sizes and shapes in the a zosteriform pattern. upper dermis.

Acta Derm Venereol (Stockh) 79 Letters to the Editor 91 nocarcinoma to the leg, as occurred in the case described here. ination (4). Manteaux et al. described a patient who developed The dermatomal distribution of the lesions accompanied by epidermotropic metastases (3). A Tzanck smear showed large neuralgia and hyperaesthesia led the physician to conclude that atypical cells which had been misinterpreted as herpetic bal- the patient had herpes zoster. loon cells. Skin biopsy revealed discohesive malignant cells This rare type of metastases has been reported in several within the subepidermal and intraepidermal vesicles. cases to date (2, 3). The primary tumours with zosteriform Smear cytodiagnosis is a rapid, accurate means of establish- metastases were located in the breast, carcinoma of the lung, ing a diagnosis of metastatic disease, especially in cases in carcinoma of the bladder, carcinoma of the renal pelvis, and which the lesions localize in the or subepidermis, carcinoma of the ovary. The frequent histopathological type and application of immunoperoxidase may qualify the cytolo- of this metastasis is adenocarcinoma, and rarely transitional gical diagnosis and location of the primary tumour. cell carcinoma. To our knowledge, this seems the ¢rst case of zosteriform cutaneous metastasis from a colonic adenocarci- noma. The vesicular appearance in our case may have been REFERENCES due to mucin production by adenocarcinoma. Some authors 1. Lookingbill DP, Spangler N, Helm KF. Cutaneous metastasis in explain this phenomenon as being caused by lymphoedema patients with metastatic carcinoma: A retrospective study of 4020 (2) and other authors by epidermotropic metastasis (3). The patients. J Am Acad Dermatol 1993; 29: 228 ^ 236. tumour cells may have been disseminated on the left lower 2. Hodge SJ, Mackel S, Owen LG. Zosteriform in£ammatory meta- extremity by lymphatic spread in the case described, because static carcinoma: Int J Dermatol 1979; 18: 142 ^ 145. direct lymphatic in¢ltration of the tumour cells was not proven 3. Manteaux A, Cohen PR, Rapini RP. Zosteriform and epidermotro- pic metastasis: J Dermatol Surg Oncol 1992; 18: 97 ^ 100. histologically and an obstruction in the left inguinal and para- 4. Pak HY, Foster BA, Yokota SB. The signi¢cance of cutaneous aortic lymph nodes had been shown in a CT scan. metastasis from visceral tumors diagnosed by ¢ne-needle aspiration Easy and prompt diagnosis of cutaneous metastases can be biopsy. Diagn Cytopathol 1987; 3: 24 ^ 29. made because skin lesions often mimic the primary tumour cytologically. In this case, tumour cells occurring in cohesive groupings or in a papillary structure were observed and the Accepted July 13, 1998. immunostaining studies displayed tumour cell reactivity for CEA, favouring intestinal adenocarcinoma as the primary Setsuko Maeda, Hiroyuki Hara and Takafumi Morishima source in a Tzanck smear. Unlike non-cutaneous metastases, Department of Dermatology. Nihon University School of Medicine, cutaneous lesions can be readily seen with careful visual exam- 1-30 Oyaguchikamimachi, Itabashi-ku, Tokyo 173-8610, Japan

Erythema Elevatum Diutinum in a Patient with Human Herpesvirus 6 Infection

Sir, on HEP2 cells (1/40 speckled IgM and IgG). Anti-HHV-6 were posi- Several cases of erythema elevatum diutinum (EED) have tive (IgM 1/80 and IgG 1/20), while antibodies against other viruses recently been found to be associated with human immunode¢- were negative or indicative of immunity. ciency virus (HIV) infection (1 ^ 3), supporting the hypothesis When ¢rst examined, the patient had been taking 30 mg de£azacort that an infectious agent plays a role in its aetiology (4). We daily for 1 month. The lesions had worsened, however, and the treat- ment was stopped. In the absence of any treatment, the lesions began to describe here an HIV-negative patient with evidence of human improve and 1 month later the anti-HHV-6 IgM titre was 1/20 and herpesvirus 6 (HHV-6) infection who developed EED. anti-HHV-6 IgG 1/80. Treatment with 100 mg dapsone daily was started. One month later, the skin lesions had clearly improved and the anti-HHV-6 IgG titer CASE REPORT decreased to 1/40. IgM were still 1/20. The drug was reduced to 50 mg daily and, 1 month later, discontinued. The disease did not relapse. In September 1996 a 50-year-old white woman in apparently good health developed a papulo-nodular eruption on the limbs. On examina- tion, she exhibited a symmetrical, di¡use papulo-nodular eruption on DISCUSSION the outer surface of thighs (Fig. 1), buttocks and ¢nger joints, and some plaques over the knees and elbows. The ear lobes and face were also EED is a rare chronic form of cutaneous of unknown involved (Fig. 2). The lesions were indurated, circinate or oval with cen- aetiology that is considered an immune-complex mediated tral atrophy, purplish to reddish-brown in colour. Neither arthralgia reaction. The disease may be associated with streptococcal nor other subjective complaints were noted. , in£ammatory bowel disease, haematological disor- A biopsy specimen showed a dense perivascular leucocytoclastic ders (4) and, less frequently, with other pathologies (4, 5) in¢ltrate in the papillary and reticular dermis consistent with EED. including HIV infection (1 ^ 3). Direct immuno£uorescence was negative. Laboratory tests including In the patient described here, an infectious cause may be sug- blood cell count, renal and liver functions were within normal ranges. gested by the exacerbation of her lesions with the steroidal There was no evidence of streptococcal infection. Chest X-rays and therapy and by their prompt amelioration with the cortico- abdominal ecography were also normal. Paraproteinaemia and cryo- globulins were absent and tumoural markers negative. steroid discontinuation (6). Immunological investigations showed only a faint ANA positivity In addition, this patient disclosed speci¢c anti-HHV-6 IgM

Acta Derm Venereol (Stockh) 79 92 Letters to the Editor

Fig. 2. Nodular lesions involving the ear lobes.

2. Requena L, Sanchez Yus ES, Martin L, Antonio B, Dolores A. Fig. 1. Papulo-nodular lesions on the thighs. Erythema elevatum diutinum in a patient with acquired immuno- de¢ciency syndrome: another clinical simulator of Kaposi's sar- coma. Arch Dermatol 1991; 127: 1819 ^ 1822. and an increase in the titre of anti-HHV-6 IgG. These serologi- 3. LeBoit PE, Cockerell CJ. Nodular lesions of erythema elevatum cal ¢ndings may be interpreted as a seroconversion during a diutinum in patients infected with the human immunode¢ciency primary HHV-6 infection or as HHV-6 endogenous reactiva- virus. J Am Acad Dermatol 1993; 28: 919 ^ 922. tion (7). 4. Yiannias JA, Rokea A, El-Azary, Gibson LE. Erythema elevatum HHV-6 infection usually occurs during infancy and persists diutinum: A clinical and histological study of 13 patients. J Am in a lifelong latent state (8). Primary infection may cause Acad Dermatol 1992; 26: 38 ^ 44. subitum in children (9), but frequently is inapparent 5. Tanzer FR, Lyn¢eld YL. Erythema elevatum diutinum. Arch Der- or results in febrile illness without any . In adults, the pri- matol 1978; 114: 802 ^ 803. mary infection is very rare, consisting of a mononucleosis-like 6. Drago F, Romagnoli M, Loi A, Rebora A. Epstein-Barr virus illness, prolonged lymphadenopathy or hepatitis (10). related persistent in chronic fatigue syn- drome. Arch Dermatol 1992; 128: 217 ^ 222. HHV-6 IgM antibodies can be detected both in primary 7. Fox JD, Ward P, Briggs M, Irving W, Stammers TG, Tedder RS. infections and in reactivation states. Anti-HHV-6 IgG antibo- Production of IgM antibody to HHV-6 in reactivation and primary dies are present in 80 ^ 90% of adults and tend to disappear infection. Epidemiol Infect 1990; 104: 289 ^ 296. over time (8). An increase in the titres of IgG to HHV-6, there- 8. Levy JA, Ferro F, Greespan D, Lennette ET. Frequent isolation of fore, is considered indicative of reactivation. In the absence of HHV-6 from saliva and high seroprevalence of the virus in the other viral cross-reactivities, such as EBV or CMV active infec- population. Lancet 1990; ii: 1047 ^ 1050. tions, the speci¢c anti-HHV-6 IgM and the increased titres of 9. Yamanishi K, Okuno T, Shiraki K, Takahashi M, Kondo T, Asano IgG make an HHV-6 endogenous reactivation most likely. The Y, Kurata T. Identi¢cation of human herpesvirus-6 as a causal rarity of the primary infection in adults and its usual severe agent for exanthem subitum. Lancet 1988; i: 1065 ^ 1067. course are additional evidences. 10. Kirchesc H, Mertens T, Burkhardt U, Kruppenbacher JP, Ho¡ken A, Eggers HJ. Seroconversion against human herpesvirus-6 (and Whether EED cutaneous lesions might be determined other herpesviruses) and clinical illness. Lancet 1988; ii: 273 ^ 274. directly by the HHV-6 reactivation state or may be a mere coincidence, cannot be established by a single case.

Accepted July 15, 1998. REFERENCES F. Drago1,M.Semino1,P.Rampini2,C.Lugani1 and A. Rebora1 1. Da Cunha Bang F, Weismann K, Ralfkiaer E. Erythema elevatum 1Department of Dermatology, University of Genoa, Viale Benedetto diutinum and pre-AIDS. Acta Derm Venereol (Stockh) 1986; 66: XV,7, 16132, Genova and 2Division of Dermatology, Gaslini Hospital, 272 ^ 274. Genova, Italy.

Acta Derm Venereol (Stockh) 79 Letters to the Editor 93 Graham Little-Piccardi-Lasseur Syndrome Following HBV Vaccination

Sir, females. LRP usually appears after the second vaccination, as As is well established, lichen ruber planus (LRP) can be asso- occurred in our case, and can be induced by all 3 types of vac- ciated with (1), whereas LRP following hepatitis B cine in common use: Hevac B (3), Gen Hevac B (7 ^ 8) (both virus (HBV) vaccination is an unusual, little known and still produced by the Pasteur Institute) and Recombivax (produced debated condition. We report here the case of a man who devel- by Merck-Sharp & Dohme). As all these vaccines share the oped Graham Little-Piccardi-Lasseur syndrome (GLPLS) same non-infective viral subunit S derived from HBsAg (4), after intramuscular HBV vaccination. we can hypothesize that this is the causal agent of LRP induced by HBV vaccination. The cutaneous reaction is probably induced by T-cell-mediated immunoreaction against keratino- CASE REPORT cytes presenting HBsAg, more speci¢cally the S protein, as A 48-year-old man, who was at risk for HBV infection as he worked as occurs in graft-versus-host reaction (5, 6). The severity of our a nurse in an emergency department, received HBV vaccine Recombi- case can be explained by the administration of the third dose vax (Merck-Sharp & Dohme, MSD). The ¢rst dose of vaccine (1 ml) despite the occurrence of LRP as a reaction to the second injec- was given to the patient in July 1995 and the second (1 ml) 4 weeks later. tion of Recombivax. This hypothesis would suggest a possible At the end of September 1995 the patient noted an eruption of numer- dose-dependant response of our patient to HBV vaccine, with ous, polygonal, red and itchy papules localized on the trunk, limbs and LRP as a ¢rst sign of GLPLS. wrists. No mucosal involvement was present. All routine laboratory tests results were normal, HBsAg and HBeAg results were negative while HBsAb and HBcAb were positive. The patient therefore con- sulted his general practitioner who diagnosed this condition as drug REFERENCES eruption and for which he prescribed antihistamines per os for 1 month. The condition healed in 6 weeks leaving a hyperpigmentation. 1. Rebora A, Patri PL, Rampini E, Crovato F, Ciravegna G. Erosive Six months after the ¢rst dose the patient received the third vaccine and cirrhotic hepatitis. It Gen Rev Dermatol 1978; 18: dose (1 ml); 5 months later spinous, acuminate, follicular papules 123^127. a¡ecting the scalp occurred. In November 1996 he consulted us. The 2. Trevisan G, Stinco G. Lichen ruber planus following HBV vaccina- dermatological examination revealed hyperpigmented polygonal, £at tion. Acta Derm Venereol (Stockh) 1993; 73: 73. papules localized on the wrists and ankles and brown spots on the lat- 3. Ciaccio M, Rebora A. Lichen planus following HBV vaccination: a eral surface of the trunk, probably the result of previous episodes of coincidence? Br J Dermatol 1990; 122: 424. LRP. On the scalp some cicatricial alopecic areas as well as di¡use alo- 4. Lefort A, Dachary D, Vergier B, Boiron G. Lichen planus and vac- pecia with ¢ne and coarse hair were present. The diagnosis of GLPLS cination against hepatitis B. Ann Dermatol Venereol 1995; 122: was therefore formulated and con¢rmed on histological examination. 701 ^ 703. The patient was treated with systemic and topical corticosteroids for 4 5. Grezard P, Philippot V, Perrot H. Lichen planus and hepatitis B vac- months, leading to healing of the hyperkeratotic papules, the alopecia cination. Two case report. Nouv Dermatol 1995; 14: 444 ^ 445. still persisting. 6. Gisserot O, Carsuzaa F, Marlier S, Morand JJ, Morrot E. Lichen planus after hepatitis B vaccination. 3 new cases. Presse Med 1997; 26: 760. DISCUSSION 7. Pusel B, Will F, Grosshans E. Lichen plan et vaccination contre GLPL is a follicular pattern of lichen planus characterized by l'he¨ patite B. Nouv Dermatol 1993; 12: 709 ^ 710. the triad: spinous or acuminated follicular lesions, typical 8. Aubin F, Angonin R, Humbert P, Agache P. Lichen planus follow- ing hepatitis B vaccination. Arch Dermatol 1994; 130: 1329 ^ 1330. cutaneous or mucosal lichen planus and alopecia of the scalp with or without atrophy. These features need not be present simultaneously. Although HBV vaccination is quite a common Accepted August 21, 1998. practice, to our knowledge LRP induced by it has been reported, until now, in only 10 cases (2 ^ 8). They were all F. Bardazzi, C. Landi, C. Orlandi, I. Neri and C. Varotti adults and they always had LRP without scalp involvement. Department of Clinical and Experimental Medicine, Division of Our case is the second induced by Recombivax (2) and the ¢rst Dermatology, University of Bologna, Via Massarenti 1, I-40138 of GLPLS, a quite rare condition more frequently observed in Bologna, Italy.

Acta Derm Venereol (Stockh) 79 94 Letters to the Editor Discordance Between DNA Analysis and the Clinical Picture in a Case of Xeroderma Pigmentosum

Sir, neurological disorders (2). In this case, the results of in vitro Xeroderma pigmentosum (XP) is a rare (2 cases/1,000,000 tests and the clinical picture were highly discordant. On the newborns), recessively transmitted genetic disease caused by basis of the clinical data (late onset of skin cancer despite many the defective repair of UV-induced DNA damage. We can years of recreational sun exposure, absence of photosensitivity, observe clinical of photosensitivity, early no involvement of other organs) our patient should be classi- skin ageing, dispigmentation and a high incidence of basal cell ¢ed in the variant group (XP-V). Laboratory examination, carcinomas (BCC), squamous carcinomas (SCC) and, rarely, however, demonstrated a reduced response of DNA repair of . XP may also be associated with ocular disor- mechanisms to UV damage. The rate of damage, that is higher ders, deafness and neurological diseases (1, 2). in the classical form of XP, is present in our patient at the low- est detectable rate. Many doubts have arisen recently about the sensibility and CASE REPORT speci¢city of the tests used to classify XP, such as complemen- We present here the case of a 76-year-old woman a¡ected by XP, which tation group analysis and UDS study (3, 4). Cell fusion may is characterized by discordance between the results of DNA analysis demonstrate enzyme de¢ciency but it cannot identify the gene. and the clinical picture. Upon anamnesis, she referred the onset of mul- Evidence of clinical and biochemical heterogeneity within indi- tiple lentigines, naevi and solar keratoses since childhood. She regu- vidual XP complementation groups has been found: for exam- larly sunbathed at the seaside and in the tropics without being ple some patients in complementation group A have severe sunburnt. She denied any hereditary disease and other dermatoses. neurological abnormalities, while others do not (4). Published When she was 54 years of age she underwent surgical excision of a data has demonstrated the limits of the UDS test: in one BCC followed, 10 years later, by the excision of 2 more BCC. In 1993, family, two brothers were found to have depressed levels of aged 73, the patient came to our department for the ¢rst time for UDS following UV irradiation, but only one of them had skin removal of a melanoma on the right cheek and a BCC on the forehead. The history of many de novo occurring cutaneous cancers and the ¢nd- cancer. The other, despite many years of occupational sun ing of many actinic keratoses on the photoexposed skin lead to a XP exposure, remained tumour-free (4). being suspected. Medical examination, routine blood tests, chest X- ray and abdominal ultrasound ¢ndings were all normal. No eye, audi- CONCLUSION tory or neurological disorders were found. A biopsy from photoprotected skin was taken to investigate the We conclude that in our patient the DNA repair system is fairly response of ¢broblasts to UVC damage (2, 3). A small reduction in e¤cient and it has worked well for many years; skin cancer the results of an unscheduled DNA synthesis assay (UDS) and in a col- appeared only after many years of exposure to the sun. Our ony-forming ability test (CFA) were demonstrated. These results were genetic probes could not have exactly located the a¡ected gene. considered compatible with a diagnosis of XP. Further studies with more speci¢c probes, which are not yet In 1995, we found a melanoma (III Clark level, 0.7 mm Breslow) and available, will let us identify the genetic defect and better clas- a SCC on the lower third of the right leg, and two BCC on the face. The patient is followed-up in our department to ensure early diagnosis and sify the patient. treatment of any new skin cancer.

REFERENCES

DISCUSSION 1. Robert C, Sarasin A. Le xeroderma pigmentosum. Que peut-on attendre des e¨ tudes biologiques? Ann Dermatol Venereol 1994; XP patients can be classi¢ed into 8 groups (Table I) on the basis 121: 434 ^ 439. of genetic defects and the di¡erent incidence of skin cancer and 2. Itoh T, Watanabe H, Yamaizumi M, Ono T. A young woman with

Table I. Xeroderma pigmentosum (4)

Disease and Number % Unscheduled DNA CFA following Skin cancer Neurological complementation of synthesis following UV disorders group patients UVC irradiation irradiation (% of normal) (% of normal)

XP-A 159 33.4 v2 v1 zzz zzz XP-B 3 0.6 3^7 zz zz XP-C 91 19.1 10^20 15 zz z XP-D 59 12.4 25 ^ 50 1 zz ^ XP-E 13 2.7 40 ^ 50 z ^ XP-F 16 3.4 10 ^ 20 40 z ^ XP-G 5 1.1 v2%;25 zzz z XP-V 130 27.3 100 z ^ Total cases 476 100

Acta Derm Venereol (Stockh) 79 Letters to the Editor 95

xeroderma pigmentosum complementation group F and a mor- Accepted July 30, 1998. phoeic basal cell carcinoma. Br J Dermatol 1995; 132: 122 ^ 127. 3. Lambert WC, Lambert MW. Diseases associated with DNA and G. Tessari1,F.S.D'Onghia1, M. Stefanini2 and A. Barba1 chromosomal instability. In Alper JC, editor. Genetic diseases of 1Department of Dermatology, University of Verona, c/o Ospedale the skin. St. Louis: Mosby Year Book 1991: 320 ^ 358. Civile Maggiore Piazzale Stefani 1 37124 Verona and 2Consiglio 4. Lambert WC, Kuo HR, Lambert MW. Xeroderma pigmentosum. Nazionale delle Ricerche ^ Istituto di Genetica Biochimica ed DermClin1995;(13)1:169^209. Evoluzionistica, Pavia, Italy.

Post-herpes Zoster Scar Sarcoidosis

Sir,

CASE REPORT A 70-year-old white woman presented a papular zosteriform eruption on her right upper thorax and right arm. Shiny, erythematous-purplish or £esh-coloured papules 2 ^ 3 mm in diameter were observed, isolated or closely arranged in little plaques (Fig. 1). The patient complained only of mild itching; no systemic signs and symptoms were referred. Two months earlier the patient had a C5 ^ C6 right brachial palsy due to brachial herpes zoster. The histopathological pattern of a papula showed a dermal non-caseating granulomatous in¢ltrate with giant Langerhans-like cells and sclerosing evolution indicating scar sarcoi- dosis. Further clinical and laboratory investigations failed to reveal systemic sarcoidosis. Chest roentgenogram and liver ultrasonography were normal; X-ray of the hands and feet did not reveal osteolytic alterations. Spirometry and ophthalmology examinations were negative, as well as Mantoux test and skin tests.

DISCUSSION The in¢ltration of scar tissue by non-caseating granulomas is a well-recognized form of cutaneous sarcoidosis (1 ^ 3). To our knowledge, it has been reported to occur in the site of previous Fig. 1. Papular zosteriform eruption of the right arm. herpes zoster only in one case (1). Most of the patients with scar sarcoidosis have other systemic manifestations, particularly pulmonary changes; scar in¢ltrates 2. Olumide YM, Bandele EO, Elesha SO. Cutaneous sarcoidosis in may appear early in the disease or before parenchymal changes. Nigeria. J Am Acad Dermatol 1989; 21: 1222 ^ 1224. 3. Veien NK, Stahl D, Brodthagen H. Cutaneous sarcoidosis in Changes in scars in patients with sarcoidosis in remission may Caucasians. J Am Acad Dermatol 1987; 16: 534 ^ 540. indicate exacerbation of the disease or may even be a marker 4. Roegel E, Pauli G, Grosshans E, El Baz D, Dietemann-Molard A, for recurrences of thoracic sarcoidosis (4). A careful and pro- Hutt JP. Sarcoides re¨ cidivantes sur cicatrices cutane¨ es re¨ ve¨ latrices longed follow-up in these patients is strongly recommended due de sarcoidose thoracique ite¨ rative. Rev Pneumol Clin 1984; 40: to the potential risk of developing systemic sarcoidosis. 81^83.

Accepted July 30, 1998. REFERENCES 1. Bisaccia E, Scarborough DA, Carr RD. Cutaneous sarcoid granu- Monica Corazza, Sandra Bacilieri and Renata Strum|© a loma formation in herpes zoster scars. Arch Dermatol 1983; 119: Dermatology Department, University of Ferrara, Via Savonarola 9, 788 ^ 789. I 44100 Ferrara, Italy.

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