Febrile ulceronecrotic Mucha-Habermann's disease with fatal outcome

A 43-year-old woman was examined in October 1993 for a widespread, large, ulceronecrotic skin eruption with exception of the mucosa (Fig. 1). The skin lesions were round and regular, varied in size from 0.5 to 2 cm, and were partially covered by a brownish-black crust. The patient had a fever ranging from 38 to 40 °C, always preceded by shivering. She had presented with small exfoliating erythematous patches and itching, 8 months before being admitted to our institute, and was treated with topical corticosteroids. After five and a half months, together with the beginning of fever, the above lesions became wet and were covered with squamous crusts. For 2 years the patient had been affected by perianal fistula, but had not referred to this pathology before. She also reported that she had been treated with antibiotic and corticosterod intravenous therapies. A biopsy specimen from a lesion of the right leg showed a widely ulcerous fragment of the skin, characterized by a strong infiltration of lymphocytes, especially in the upper part of the dermis, with neutrophil granulocytes. The epidermis surrounding the ulcer showed acanthosis, orthokeratosic hyperkeratosis, and spreading lymphocyte exocytosis, with a large number of necrotic keratinocytes and the presence of melanophages (Figs 2 and 3), All the above data suggested a diagnosis of pityriasis lichenoides et varioliformis acuta (PLEVA). Direct immunofluorescence carried out on perllesional skin showed the presence of fluorescent bodies on the superficial dermis using antisera anti-immunoglobulin (anti-IgM) and Ciq. Laboratory tests showed the following values: erythrocyte sedimentation rate (ESR), 55 LVh; C-reactive protein, 85 mg/L; white blood cell (WBC), 9200 g/dL; platelets, 476,000; gamma glutamil transferase, 93 U/L; alkaline phosphatase, 185 IU/L; complement C3 fraction, 70.9 mg/L; CP4/CD8 lymphocyte ratio, 6.5; total IgE, 2493 ku/L. Human immunodeficiency virus (HIV), Epstein-Barr virus (EVB), cytomegalovirus, herpes simplex 1 and 2, toxoplasma, rickettsia, and hepatitis markers A, B, and C gave negative results, while blood cultures were positive for Staphylococcus aureus and Pseudomonas aeruginosa. Circulating immune complexes (as C1 binding system), 80 (im/eq/L (normal value, less than 20). Qhest X-ray and total body computed axial tomography (CAT) scan were negative. Antimicrobial therapy with teicoplanin and trimethoprim + sulfamethoxazole for 15 days resulted in a reduction in microbial count in blood cultures, and therapy with prednisone (60 mg/day) for a further 20 days was started. The patient was discharged from hospital in reasonable physical condition, without fever and with an improvement of the skin lesions. Surgery for the treatment of her perianal fistula was not performed as her general condition had improved- The patient continued therapy at home with 50 mg prednisone and a broad spectrum antimicrobial for a further 20 days. One month later, the patient was admitted to hospital in a poor physical condition with fever (peaks of 40/41 °C), preceded by shivering, relapsing skin ulcers, weak respiration, and polypneia. The laboratory tests showed a serious hypoproteinemia, C-reactive protein concentration of 321 mg/L, and high transaminase levels. Blood analysis was positive for Staphylococcus aureus. Therapy was started with 60 mg prednisone, antimicrobials, and albumin, but 24 h later the patient fell into a coma and died from cardiogenic shock. Upon her family's request, no autopsy was performed.     

Pustular panniculitis in a patient with rheumatoid arthritis

A 51-year-old woman presented with a 10-day history of painful red swelling of the right lower leg. She had been treated with prednisolone for classic (seven criteria according to the American Rheumatism Association), seropositive, rheumatoid arthritis of 5 year's duration. She had received prednisolone at an initial dose of 60 mg/day, with gradual tapering over 16 weeks to a final dose of 7.5 mg/day. In addition, mizoribine (immunosuppressive agent) 100 mg/day was administered for 2 months. Examination of the skin revealed erythematous lesions with shiny surfaces that were markedly swollen and involved the entire right lower leg, with partial violaceous, eroded areas, and bullous formation (Fig. 1). Extensive fat necrosis was accompanied by necrosis of the overlying skin, and a large amount of an oily, yellow serous liquid, approximately 200 mL, was discharged from the lesions. There were no sign or symptom of arteritis or venous insufficiency. A skin biopsy showed prominent edematous change in the reticular dermis, and perivascular inflammatory cell infiltrate. In addition, lobular and septal panniculitis with fat necrosis accompanied by a massive cellular infiltrate consisting of numerous neutrophils, neutrophilic dust, and occasional eosinophils, was observed mainly in the subcutaneous lobules and partially in the septa (Fig. 2). Leukocytoclastic vasculitis of the whole dermis, involving small and medium-sized arteries and venules, with fibrlnoid necrosis of the vessel walls, was present. However, no deposition of immunoglobulins and complements was demonstrated on immunohistopathologic examinations. The overall thickness of the subcutaneous space had collapsed, leaving extensive microcysts lined by membranous fat necrosis and filled with massive neutrophilic and eosinophilic infiltrate. Stains for organisms, including acid-fast bacteria, were negative. Laboratory studies showed anemia (hemoglobin, 10.3 g/L), elevated erythrocyte sedimentation rate;.,. (98 mm/h), white blood cell count (8000/μL), increased levels of aspartate aminotransferase (44 U/L), alanine aminotransferase (41 U/L), alkaline phosphatase (29.1 King-Arnnstrong Unit), Leucine amino peptidase (567 lU/L), gamma-glutamyl transferase (483 IU/L), hepatitis B antigen (5361 U/mL), hepatitis B antibody (13.3 mU/mL), circulating immune complexes (9.8 (xg/mL), and positive rheumatoid factor (40 IU/mL), positive antinuclear antibody test (1: 640) in a speckled pattern, without anti-DNA, and a decreased complement level of C4 (11.5 mg/dL). Serum protein electrophoresis showed hypergamma-globulinemia (40.7%). Hepatitis C antibody, C-reactive protein, cryogiobulin, complement level (CH50, C3), extractable nuclear antigen (Sm, RNP), amylase, alpha-1 antitrypsin inhibitor, chest roentgenogram, and electrocardiogram were within normal limits or revealed negative findings. No organisms were cultured from repeated swabs. Treatment with prednisolone 60 mg (2 mg/kg)/day along with methotrexate 10 mg/week was started. Shortly after, the erythematous swelling of the affected leg regressed moderately and within 4 weeks the ulcers became clean and were totally healed. The dose of prednisolone was decreased to 25 mg/day along with methotrexate 10 mg/week, but no relapse has occured during the 8 months’follow-up.     

Extranodal NK/T-cell lymphoma, nasal type, presenting after 5 years of remission

A 76‐year‐old woman with multiple edematous erythemas, erosions, and ulcers on the breast and abdomen was admitted to our hospital in June 2005. She had developed granulomatous bleeding lesions in the right nostril 6 years prior to her visit to our dermatology unit. She had been observed at the otorhinolaryngology department of our hospital, and a biopsy was taken from the nasal lesion. Computerized tomography and gallium scintigraphy (⁶⁷Ga single‐photon emission computed tomography) did not reveal any lesions corresponding to the diagnosis of malignant lymphoma. The histologic examination of the nasal specimen rendered a diagnosis of natural killer (NK)/T‐cell lymphoma, nasal. Because imaging analysis indicated a small‐sized tumor without metastases, oral prednisolone at 20 mg/day was administered for 1 month. The tumor decreased in size and disappeared after 19 months of low‐dose steroid therapy. Five years after the initial treatment, the patient developed a fever of 38 °C with infiltrated erythemas and erosions on her breast. Erysipelas was initially suspected, but the antimicrobial agent did not show any effect and the multiple infiltrated erythemas and ulcers spread throughout her chest and abdomen ( Fig. 1 ). The lymph nodes were not palpable. The right nasal cavity showed no granulomatous lesions or other signs of abnormality. The peripheral white blood cell count (3000/µL), red blood cell count (3.54 × 10⁶/µL), and platelet count (112 × 10³/µL) were reduced. Atypical lymphocytes were not observed. The serum lactic dehydrogenase (LDH; 1770 U/L; normal, 224–454 U/L), aspartate aminotransferase (AST; 140 U/L; normal, 10–30 U/L), and alanine aminotransferase (ALT; 57 U/L; normal, 3–29 U/L) levels were elevated. The soluble interleukin‐2 (IL‐2) receptor level was high (25,300 U/mL; normal, 167–497 U/mL). Epstein–Barr virus (EBV) serologic examination showed the immunoglobulin G (IgG) viral capsid antigen (VCA) at 1 : 320 and the EBV nuclear antigen (EBNA) at 1 : 40. IgM VCA and EBV early antigen‐diffuse restricted antibody (EA) IgA and IgG were not detectable. Histologic findings from the left chest skin showed a distribution of atypical lymphocytes from the upper dermis to the subcutaneous tissue, and many foamy cells which had phagocytosed the hemocytes ( Fig. 2a,b ). Immunohistochemical analysis showed that the atypical lymphocytes were sCD3–, CD4–, CD8–, CD20–, CD56+, granzyme B+, and T‐cell intracellular antigen (TIA‐1) positive. Furthermore, EBV‐encoded small RNAs (EBER), detected by in situ hybridization, exhibited a strong signal. The nasal lesions biopsied 6 years previously showed an identical staining pattern with the skin lesions immunohistochemically. Analysis of the T‐cell receptor‐β (TCR‐β), TCR‐γ, and TCR‐δ gene did not reveal any clonal rearrangements, but the EBV gene was detected from the skin specimens by Southern blotting. Our patient's condition was diagnosed as a case of extranodal NK/T‐cell lymphoma, nasal type, but the patient had concomitantly developed hemophagocytic syndrome (HPS). She was treated with a combination of steroid pulse therapy and chemotherapy (pirarubicin hydrochloride 30 mg/m², cyclophosphamide 500 mg/m², vincristine 1 mg/m², prednisolone 30 mg/m², etoposide 80 mg/m²). After the first session of chemotherapy, the lesions on the chest and abdomen diminished, but, 2 weeks later, the skin lesions recurred, and disseminated intravascular coagulation (DIC) induced by HPS supervened. The patient died as a result of multiple organ failure induced by HPS.

Figure 1 Open in figure viewer PowerPoint Multiple infiltrated erythemas, erosions, and ulcers on the breast and abdomen     

CD4/CD8 double-positive, acute type of adult T-cell leukemia/lymphoma with extensive cutaneous involvement

A 67‐year‐old Korean man presented with a 2‐week history of pruritic cutaneous lesions on the trunk and a 2‐month history of cervical neck masses. The cutaneous lesions had been spreading rapidly for the last week. The past history included an unknown liver disease about 40 years previously, and he had never been transfused. The physical examination revealed multiple cervical lymph node enlargements and a two‐finger width of splenomegaly with tenderness. Numerous nodules and plaques were distributed on the trunk, face, and proximal extremities ( Fig. 1 ). The results of laboratory tests were as follows: leukocyte count, 24,200/mm³, with lymphocytes 15,560/mm³; serum lactate dehydrogenase, 943 IU/L (normal range, 263–450 IU/L); alkaline phosphatase, 135 IU/L (normal range, 35–60 IU/L); blood urea nitrogen, 32 mg/dL (normal range, 3–24 mg/dL); serum creatinine, 1.7 mg/dL (normal range, 0.3–1.6 mg/dL); serum calcium, 17.5 mg/dL (normal range, 8.8–10.2 mg/dL). Other laboratory results, including liver function test and urine analysis, showed no abnormalities. The examination of peripheral blood revealed multilobulated atypical lymphoid cells. The radiologic images showed hilar, para‐aortic lymph node enlargement and splenomegaly. A skin biopsy from the nodular lesion revealed massive infiltration of small‐ to medium‐sized atypical lymphoid cells in the dermis ( Fig. 2a ). The infiltrating cells were positive for CD3 ( Fig. 2b ), CD4 ( Fig. 2c ), CD5, and CD8 ( Fig. 2d ), but negative for CD20, CD34, CD56, CD68, and terminal deoxynucleotidyl transferase (TdT) in the immunohistochemical studies on paraffin sections. They also showed high Ki‐67 labeling (80–90%), and this finding reflects their highly proliferative nature. Polymerase chain reaction (PCR) analysis showed a distinct band for the T‐cell γ receptor gene, confirming the T‐cell clonality of the infiltrating neoplastic cells. Specimens from the cervical lymph node and bone marrow showed the same results in immunohistochemical studies. PCR analysis of the DNA from peripheral leukemic cells showed human T‐cell leukemia virus type I (HTLV‐I) proviral integration. The patient was diagnosed as having the acute type of adult T‐cell leukemia/lymphoma (ATLL). The disease course was extremely aggressive, and he died of acute renal failure on the 16th day following diagnosis.

Figure 1 Open in figure viewer PowerPoint Pruritic erythematous nodules and plaques on the face, trunk, and upper arms     

Complete resolution of psoriasis vulgaris after excision of thyroid cancer

A 61-year-old woman was seen with a 1-month history of a widespread eruption over the trunk and extremities. She also had an asymptomatic tumor in the neck that had developed 8 years earlier. Examination revealed generalized, erythematous scaling plaques over the trunk, arms, and extremities (Fig. 1). An ultrasound and radioisotope scan of the neck disclosed a soft tissue mass compatible with thyroid carcinoma.
Laboratory tests showed a white cell count of 9.8X10⁹/L, and triiodothyronine, thyroxin, and calcium levels within the normal range. The thyroid-stimulating hormone (TSH) level was 6.3 μIU/mL (normal range 0.33–3.6 μIU/mL), and thyroglobulin was 320 μg/mL (normal range 14–31 μg/mL).
A skin biopsy specimen from the upper portion of the arm showed hyperkeratosis with focal parakeratosis and elongation of the rete ridges. The dermis showed mild papillary edema and perivascular lymphocytic infiltration compatible with psoriasis vulgaris. After the biopsy, ampicillin, 1000 mg daily, was administered for 21 days; however, the lesions were unchanged. The patient was then operated on with excision of the thyroid cancer and the regional lymph nodes. Histopathologic examination disclosed an adenocarcinoma of the thyroid; the lymph nodes were infiltrated by tumor cells. After the operation, cefazolin, 2000 mg daily, was given for 9 days. At 2 weeks postoperatively, the lesions began to subside without any dermatologic treatment and then resolved completely within 1 month of the operation (Fig. 2). Three weeks after the excision of the tumor, the patient started to receive levothyroxine sodium (T4), 0.1 mg daily, to compensate for low thyroid hormone production. Within the second postoperative month, TSH, triiodothyronine, and thyroglobulin returned to normal. After excision of the carcinoma, her psoriatic lesions, remained in remission for an additional 5 months without any dermatologic treatment.     

Retroperitoneal round-cell liposarcoma associated with paraneoplastic pemphigus presenting as lichen planus pemphigoides-like eruption

A 59-year old Caucasian woman refugee from Bosnia had been in good health until a year before admission, when she developed painful erosions and ulcerated lesions in the mouth, anogenital area, hands, and feet. Treatment with topical and systemic antibiotics, acyclovir, and antifungal creams was ineffective. Three months before admission, her skin and mucosal lesions had worsened, resulting in the limitation of walking and her daily activities. She had also experienced significant weight loss. On admission to the Department of Dermatology, University of Belgrade, the patient was noted to be thin, distressed, and quite depressed. Physical examination reveaied ulceration that involved the floor of the mouth, ventral and laterai tongue, buccai mucosa, and hard and soft palate (Fig. 1). The vermiiion surfaces were fissured, eroded, and crusted with shiny vioiaceous scaiy papules dispersed across the cutaneous edge of both upper and iower lip (Fig. 1). Skin examination disciosed scattered vioiaceous scaiy lesions on the fiank, wrists, dorsa of the hands and feet, and lower legs. There were numerous erosions with livid erythema on the palms and soles, fingers and toes, with fissured naiis, partial and totai onycholysis, and pterygium formation. On the vulvar and vaginai mucosa, as well as the anal and perianal area, numerous erosions with erythema and white exudate were aiso present. On the skin of the anterior abdomen, both axillas, and right groin, large tense blisters were noticed. In the right lower quadrant of the abdomen, a firm, painful, ill-defined mass was palpated, approximateiy 15 cm beiow the right costal margin. A pelvic examination confirmed a hard, immobile, painful, abdominai mass, with the suggested origin from the right adnexai (tubo-ovarial) region. Abdominal and peivic sonogram, as well as CT scan revealed a 10x9 cm, right-sided retroperitoneal tumor. Chest rentgenogram, and CTscan of the lungs were within normal limits. Laboratory studies revealed normocytic, normochromic anemia with hypoalbuminemia. The following analyses were negative or within normal limits: antinuclear antibodies, cryogiobulins, VDRL, cultures for Candida and Herpes virus from oral and perianal mucosa. A biopsy specimen from the orai mucosa demonstrated acantholytic blister with keratinocyte necrosis and vacuolar interface changes. A biopsy of the violaceous papules from the wrist, finger and lower legs showed hyperkeratosis, hypergranulosis, dyskeratotic keratinocytes, prominent vacuolar interface changes, lichenoid infiltrate with exocytosis of mononuclear celis and superficial, subcorneal clefting in one specimen (Fig. 2). Biopsy of the tense blister from the anterior abdomen disciosed subepidermal bulla consistent with bullous pemphigoid. Direct immunofluorescence (DIF) of perilesional skin and oral mucosa revealed intercellular binding of IgG as well as diffuse deposition of IgG and C3 along with dermoepidermal junction. Indirect immunofluorescence (IIF) studies of the patient serum revealed strong intercellular binding on human skin (titer 1:640) as well as on transitional epithelium of rodent urinary biadder (titer 1:40) (Fig. 3). Immunoprecipitation studies were not available at the time of hospitalization and were not performed. Two weeks after the admission, the tumor was resected. Final pathoiogicai diagnosis was consistent with encapsulated round-oeii liposarcoma. No metastatic spread was observed through the tumor capsule into the surrounding tissue. After tumor resection, the patient was treated with prednisone (0.75–1.0 mg/kg) and azathioprine (100 mg/day) with significant improvement of skin lesions in the following 2 weeks. The mucosal lesions were however still active with slow, but progressive, epitheliazation of the erosions. At the time of discharge, late in November 1993, her prednisone dose was tapered to 0.5 mg/kg, with azathioprine 50 mg/day, with almost complete healing of the oral lesions. Her general health condition was satisfactory, and no signs of metastatic diseases were evident. Since discharge, the patient has never returned to our department, and was subsequently lost to follow-up.     

A case of recurrent Sweet's syndrome in an 80-year-old man: a clue to an underlying malignancy

An 80-year-old man presented with multiple erythematous papules on the trunk and extremities of a few weeks' duration. He had no past medical or family history of skin diseases or any other medical diseases. A biopsy showed a perivascular lymphohistiocytic infiltrate and sparse neutrophils with several atypical lymphocytes in the deeper dermis. With an initial diagnosis of T-cell pseudolymphoma or unspecified neutrophilic dermatosis, he showed a brisk response to an intramuscular injection of triamcinolone acetonide (40 mg/mL). After 1 month, his skin lesion recurred. Steroid was given with a good clinical response. One month later, however, his skin lesion relapsed. At this time, he presented with disseminated pustulopapular lesions on the trunk and extremities. Examination revealed multiple, variable-sized, erythematous plaques with central pustules on the extremities (Fig. 1). The mucous membranes were not involved. He had no pain or tenderness. He had no systemic symptoms. Laboratory tests showed a hemoglobin level of 10.3 g/dL, a leukocyte level of 6,900/mm(3), with an increased proportion of segmented nuclear neutrophils (83%), and an elevated C-reactive protein. A skin biopsy revealed a dense perivascular and interstitial infiltrate composed of neutrophils with marked dermal edema (Fig. 2). Sweet's syndrome was the final diagnosis and he was treated with oral prednisolone (30-40 mg/day) and dapsone (50 mg/day) for 2 months. As this 80-year-old patient had a recurrent history of similar skin lesions and anemia, an underlying hematologic malignancy was suspected. A bone marrow biopsy showed typical myelodysplastic syndrome (MDS). The hemoglobin level was decreased to 5.3 g/dL during a follow-up period of 5 months. The skin lesions recurred despite oral steroids and dapsone. The patient received only symptomatic treatment, such as a transfusion, for the underlying malignancy MDS.     

Nodular fat necrosis associated with lupus-induced pancreatitis

A 29–year-old black vi/oman presented with a 6–year history of lupus nephritis, cerebritis, arthritis, and recurrent facial erythema. She was admitted to the National Naval Medical Center following an acute lupus flare manifested by the onset of acute tubular necrosis requiring the initiation of hemodialysis. The patient had also developed a Staphylococcus aureus septicemia secondary to an infected IV site. During the first and second weeks in hospital, the patient responded well to aggressive antibiotic therapy and oral prednlsone. As the oral prednisone was decreased from 60 mg to 40 mg per day on day 19 in hospital, the patient developed several tender, erythemafous, subcutaneous nodules over the lower extremities (Fig. 1). There was no cutaneous ulceration or drainage. Although the initial clinical diagnosis was erythema nodosum, a deep incisional biopsy was performed to rule out infectious, vasculitic, or lupus panniculitis. Histologic findings of a representative leg nodule included lobular panniculitis with extensive fat necrosis,' ghost cell' formation, acute suppurative inflammation, and focal calcification (Fig. 2). Stains and cultures for organisms were negative. These findings were felt to be pathognomonic for nodular fat necrosis associated with pancreatic disease. Laboratory data revealed serum amylase and lipase to be markedly elevated at 1342 U/L (A/=28–110 U/L) and 4160 U/L (W=7–60 U/L), respectively; white blood cell count and differential were within normal limits. Other significant laboratory data included an anti-DNA of 692 lU/mL (A/=<100 IU/mL) and positive anti-Sjogren's syndrome-A. Simultaneous punch biopsy of an erythematous facial macule revealed epidermal atrophy, vacuolar interface change, and a mild perivascular and periadnexal lymphohistiocytic infiltrate, consistent with lupus erythematosus. Computed tomography (CT) scan and ultrasound exannination of the abdominal cavity failed to provide further evidence of pancreatitis. Although the patient was initially asymptomatic, 1 week following the onset of her leg nodules she developed severe ankle and knee arthralgias, abdominal pain, nausea, and vomiting which were attributed to her pancreatitis. She was treated with high-dose prednisone and Cytoxan for control of her lupus flare, which brought about the resolution of her leg nodules and associated symptoms over the following 6 weeks. Only post-inflammatory hyperpigmentation remained in the skin overlying the sites of nodular fat necrosis.     

Acantholytic dermatosis in chronic renal failure

A 53-year-old Chinese man with chronic renal failure complained of persistent small raised papules behind the ears and on the nape of the neck for the past 6 months. These lesions were slightly pruritic but nontender. He was diagnosed as having chronic renal failure secondary to chronic glomerulonephritis and had been on maintenance hemodialysis for the past 9 years. He had pulmonary tuberculosis 18 months earlier and had completed a full course of antituberculous therapy consisting of 2 months of 800 mg/day ethambutol, and 9 months of 450 mg/day rifampicin and 300 mg/day isoniazid. His present medications included 100 mg/day asprin, 0.25 μg/day calcitriol, daily calcium, and multivitamin supplements which he had been taking for the past 3 years. He worked mainly on a night shift as a cab driver for the past 20 years and gave no history of excessive sun exposure. There was no family history of any acantholytic disorder. Physical examination revealed an anemic patient with pallor and the sallow discoloration of chronic renal failure. Multiple discrete, brownish scaly papules (approximately 20 in number), measuring between 2 and 6 mm in diameter, were clustered behind both ears and on the nape of the neck just below the hairline (Fig. 1). Some of the firm papules had a central depression. The rest of the body was unaffected. There were no signs of significant sun damage present. Laboratory tests showed the following: hemoglobin 7.6 g/dL, white blood cell count 8000/mm³, platelets 234,000/mm³, urea 21.0 mmol/L, Na 135 mmol/L, K4.8 mmol/L, Cl 101 mmol/L, HCO₃20.0 mmol/L, blood glucose 5.9 mmol/L, creatinine 1176 nmol/L, total calcium 2.39 mmol/L, and inorganic phosphate 2.29 mmol/L. On biopsy, the papular lesions showed suprabasal clefts, focal acantholysis with corps ronds, and grains (Fig. 2). The adjacent dermis showed patchy infiltrates of lymphocytes and mononuclear cells. The histologic findings resembled Darier's disease. Most of the skin lesions were excised and followed by primary skin closure. No recurrence was noted after 6 months of follow-up.     

Drugs and Wells' syndrome: a possible causal relationship?

In April 1997, a 28‐year‐old woman presented with a 3‐day history of multiple papules and vesicles on the fingers and wrist of her right hand. She reported that she had been taking nonsteroidal anti‐inflammatory drugs containing tenoxicam and diclofenac sodium, and had no history of an insect bite. The medical history also included pruritic erythema on her trunk 1 month before her initial visit, and oral tenoxicam and diclofenac sodium treatment for ankle arthralgia 2 days before the skin lesions appeared. At that time, her dermatologist had told her that the skin lesions might be due to an insect bite and were secondarily infected. She took amoxicillin for the lesions, and during the following days developed bullous lesions on her hands and feet. The patient was diagnosed with ‘‘drug reaction’' at another hospital based on a histopathologic examination of the affected skin. Treatment with topical corticosteroids and oral antihistamines was ineffective. Physical examination revealed a few crusted, erythematous, papular lesions on the dorsal aspects of the patient's feet, bullous lesions on her right wrist, and vesiculopapules on her fingers. She had no fever or other abnormal clinical findings. Laboratory studies showed a white blood cell count of 6000/mL with 16.5% eosinophils. A bacterial culture of the content of one of the bullous lesions was negative. The results of stool tests for parasites and ova were negative. Clinical and laboratory findings were in line with the diagnosis of drug reaction. The patient was advised not to take nonsteroidal anti‐inflammatory drugs. The skin lesions resolved rapidly on treatment with wet compresses of Burow's solution and oral prednisolone (40 mg/day). The dose of prednisolone was gradually reduced, and was discontinued after 3 weeks. The patient was readmitted in July 1997 for an indurated, erythematous plaque on her left foot, a lesion that resembled cellulitis. Her history at that time included the initiation of amoxicillin treatment for a gingival abscess 2 days before the skin lesion appeared. The lesion regressed after amoxicillin was discontinued and the patient received an intramuscular injection of triamcinolone acetonide. Several months later, in October 1997, she developed a similar cellulitis‐like lesion on her right ankle. This time there was no history of drug intake. We obtained a skin biopsy from the lesion, and histopathology revealed an intense eosinophilic infiltrate in the dermis and extending into the subcutaneous tissue. Flame figures were abundant ( Fig. 1 ). We also observed edema and erythrocyte extravasation in the dermis. Based on these features and her history, a diagnosis of Wells' syndrome was made. The skin lesion resolved spontaneously, and she has experienced no lesion recurrence since.

Figure 1 Open in figure viewer PowerPoint A characteristic ‘‘flame figure’' (hematoxylin and eosin stain; original magnification, × 230)     

CAROTENODERMA: A POSSIBLE PIT-FALL IN THE IMMUNOPATHOLOGIC DIAGNOSIS OF PEMPHIGUS VULGARIS

A 30-year-old woman presented with an orange-yellow discoloration of the skin, most noticeable on the palms and soles and nasolabial folds; sclera appeared normal. The patient had observed the abnormal pigmentation of her skin 3 months earlier and noticed that it had become more evident after a sauna she had taken 2 days before our examination. In the last 3 years the patient's diet included about 2 kg of oranges daily (which are notoriously rich in carotene) following her own original idea. Complete laboratory analyses were normal. In particular, thyroid and liver function tests were in the normal range as were serum lipid levels. The serum carotene levels were 410 mg/dL (NV 20-150 mg/dL) and the levels of vitamin A 68 mg/dL (NV 25-60 mg/dL). A punch biopsy, taken from the palm of the right hand, observed under an optic microscope showed an autofluorescence in the superficial horny layer and a pemphigus-like pattern of intercellular autofluorescence. A month after the interruption of the orange-rich diet, the abnormal coloration of the skin disappeared and serum levels of carotene and vitamin A were normal.     

A randomized parallel trial of topical aspirin–moisturizer solution vs. oral aspirin for acute herpetic neuralgia

BACKGROUND: In this study, the efficacy of oral aspirin vs. topical aspirin in moisturizer (Vaseline Intensive Care Lotion) was studied in an open, randomized, parallel trial in patients with acute herpetic neuralgia. METHODS: Thirty patients were evaluated in the trial, with 15 in each group. The patients were randomized to receive either oral aspirin, 375-750 mg three times a day, or 75 mg topical aspirin/mL of moisturizer (5-10 mL, depending on the extent of involvement), three times a day, for 21 days. Pain was assessed daily by means of a self-rating visual analog scale and physician assessment. In addition, the skin and plasma levels of aspirin were measured in both groups. RESULTS: The mean time to onset of pain relief was 44 min with topical aspirin and 110 min with oral aspirin. The mean duration of pain relief after a single application of topical aspirin was 5.4 h, whereas it was 3.5 h with oral aspirin. The mean visual analog scale scores for pain with oral aspirin decreased from 68.2 +/- 6.1 on day zero to 43.1 +/- 8.7 on day 21, which was not significant compared with the baseline score. With topical aspirin, the baseline pain score was 77.5 +/- 3.7 and decreased to 6.8 +/- 3 on day 21 (P < 0.001 compared to the baseline score and compared to oral aspirin). The mean plasma and skin levels of aspirin following oral administration were 16.21 +/- 1.1 microg/mL and 1.97 +/- 0.3 microg/mm2, respectively. After topical administration, the mean plasma level of aspirin was 2.29 +/- 0.5 microg/mL (P < 0.01 vs. oral aspirin) and the skin level was 5.96 +/- 0.4 microg/mm2 (P < 0.05 vs. oral aspirin). Treatment tolerance was excellent in both groups. CONCLUSIONS: This trial has demonstrated that topical aspirin in moisturizer is clearly superior to oral aspirin in relieving the pain of acute herpetic neuralgia, and that the analgesic activity of aspirin is largely due to its local effect.     

Multiple keratoacanthomas in a young woman: report of a case emphasizing medical management and a review of the spectrum of multiple keratoacanthomas

A 27-year-old white woman was referred for consultation with regard to the presence of extensive multiple keratotic lesions. She began to develop these lesions at the age of 9 years, with healing of the lesions resulting in scar formation. A biopsy was performed at the age of 16 years, but the patient was unsure of the results. Since then, she had not had any treatment or biopsies, and stated that she had not suffered from any health problems during the intervening period. She was most concerned about the tumors on her heels and soles, which caused difficulty with ambulation. The family history was negative for skin diseases, including melanoma, nonmelanoma skin cancer, psoriasis, and eczema, and positive for Type II diabetes mellitus. A relative reported that the patient's grandfather had similar lesions, but the patient's parents and siblings were healthy. She was married and had one child, a 9-year-old daughter. Her child had no skin lesions. The patient's only medication was Ortho-Tricyclene birth control pills. She had no known drug allergies. Physical examination revealed the presence of multiple lesions on her body (Fig. 1). Her left superior helix contained a well-demarcated, dome-shaped nodule with a rolled, mildly erythematous border with a central hyperkeratotic plug. A similar lesion was present in the scaphoid fossa of the left ear and smaller lesions were scattered on her face. Numerous lesions were present on the arms and legs bilaterally, with the majority of lesions being located on the anterior lower legs. There were also lesions present on the palms and soles. The lesions ranged in size from 5 mm to 3 cm, the largest being a verrucous exophytic nodule on the anterior aspect of her left leg. Overall, there appeared to be two distinct types of lesion. One type appeared round, oval, and symmetric with a central keratotic plug, similar to that on the ear. The other type was larger, more exophytic, and verrucous, including the lesions on the volar surfaces. Also present were numerous, irregularly shaped atrophic scars where previous lesions had healed spontaneously. There were no oral lesions or lesions on her fingernails or toenails, and her teeth and hair were normal. A biopsy was obtained from an early lesion on the right dorsal forearm. Histology revealed an exo-/endophytic growth having a central crater containing keratinous material (Fig. 2). The crater was surrounded by markedly hyperplastic squamous epithelium with large squamous epithelial cells having abundant glassy cytoplasm. Some cells were dyskeratotic. Within the dermis was a dense, chiefly mononuclear inflammatory infiltrate. A buttress of epidermis surrounded the crater. The clinical and pathologic data were consistent with keratoacanthomas. Initial laboratory screenings revealed elevated triglycerides and total cholesterol, 537 mg/dL (normal, < 150 mg/dL) and 225 mg/dL (normal, < 200 mg/dL), respectively, with all other laboratory results within normal limits. In anticipation of starting oral retinoid therapy for her multiple keratoacanthomas, she was referred to her primary care physician for control of hyperlipidemia. After her lipids had been controlled, she was placed on isotretinoin (Accutane) 40 mg/day. There was some interval improvement with regression of some lesions leaving atrophic scars. She was also started on topical application of tazarotene (Tazorac) for all nonresolving lesions. Possible side-effects from the isotretinoin occurred, including dry mouth and eyes. After 8 months of isotretinoin, the patient was switched to acitretin (Soriatane) 25 mg to determine whether it might have a more beneficial effect on the resistant lesions. Many of the larger lesions regressed leaving atrophic scars. The dose of acitretin was subsequently increased to 35 mg because the lesions on her heel and the ball of her foot persisted. Almost all of the lesions resolved, except those on her feet, which are slowly regressing. Currently, the patient is on a regimen of acitretin 25 mg once a day with tazarotene 0.1% gel applied directly to the few residual keratoacanthomas on her feet, which are slowly improving.     

Juvenile mycosis fungoides treated with bexarotene and PUVA

A 14-year-old Caucasian boy presented with a 4-month history of a slightly pruritic eruption that began on the hips and later extended to the trunk and upper and lower limbs. The patient did not present fever, weight loss, or asthenia. Physical examination revealed multiple, red, desquamative, oval patches with areas of healthy skin between them, which covered nearly 50% of the body surface area. The palms, soles, face, and mucosa were not affected. In addition, he presented two violet-colored infiltrated plaques on the left thigh and right buttock (Fig. 1). There were multiple, > 1 cm, freely mobile, axillary and inguinal nodes. In follow-up, the patient developed two red-colored, mobile, well-delimited cutaneous nodules of 2.5 cm in diameter in the right hemithorax and lumbar area. The lumbar nodule regressed spontaneously before treatment. The clinical diagnosis was mycosis fungoides. We obtained three skin biopsies, one from a patch lesion and the others from a nodule; the third was sent to a reference hospital to determine the rearrangement. Histologic examination was similar in the three biopsies and revealed an atypical lymphoid infiltrate in the superficial dermis with epidermotropism and a tumoral nodule of atypical, small-sized lymphocytes in the deep dermis and subcutaneous level (Fig. 2). The atypical infiltrate was CD3+, CD4+, CD8-, T-cell intracellular antigen (TIA)+/-, Epstein-Barr-encoded RNA (EBER)-, and CD56-. The biopsy of one left axillary adenopathy was compatible with mycosis fungoides (Fig. 3). Amongst the additional tests carried out was a blood analysis showing 5300 leukocytes (neutrophils, 35%; lymphocytes, 40.7%; monocytes, 16.8%; eosinophils, 6.40%) without Sézary cells, normal lactate dehydrogenase (LDH), immunoglobulin E (IgE) of 497 U/mL (normal, 3-100 U/mL), and beta2-microglobulin of 3.09 mg/L (normal, 1.64 +/- 0.58 mg/L). A bone marrow study and a thoraco-abdomino-pelvic scan were normal. The rearrangement in the skin was monoclonal, whereas in peripheral blood and lymph nodes it was polyclonal. With the diagnosis of mycosis fungoides stage IVA (according to the TNM classification), treatment was initiated with psoralen plus ultraviolet light A (PUVA), three times a week, plus oral bexarotene at a dose of 300 mg/m2/day. The parents were informed that this treatment was not approved for this age group and informed consent was obtained. The clinical tolerance to bexarotene was very good, although low doses of atorvastatin (10 mg/day) and 75-100 mg of thyroxine were needed to control the expected adverse reactions to oral retinoid. After 32 sessions of PUVA and 6 months of treatment with oral bexarotene, the skin patches regressed, except for the plaque on the left buttock and the nodule on the right hemithorax (Fig. 4). There was no evidence of lymphadenopathy clinically or via sonographic evaluation. Bexarotene was discontinued after patient clearance and resolution of adenopathies. Nevertheless, 5 months after discontinuation of oral treatment, the patient developed multiple, scaling, nonconfluent macules on the trunk and arms affecting almost 30% of the body surface area, which disappeared with the application of methylprednisolone aceponate. He did not present significant lymphadenopathies.     

小儿获得性二期梅毒1例

患儿女,4岁。外阴、肛周皮损1月余,伴虫蚀样脱发半月余。皮肤科情况:外阴、肛周可见红色湿性斑块,肛周皮损表面覆灰白色薄膜及分泌物。RPR1:32(+),TPPA(+)。诊断:小儿获得性二期梅毒。予苄星青霉素肌内注射治疗后皮损基本消退。     

Lichen planus pemphigoides: report of two cases

Case 1 A 73‐year‐old woman with a 5‐month history of widespread lichenoid eruption developed disseminated blisters. She had insulin‐dependent diabetes mellitus and renal tuberculosis treated with isoniazide (300 mg/day), rifampin (600 mg/day), ethambutol (1.5 g/day) and pyrazinamide (2 g/day) following right nephrectomy. Antituberculous therapy which had been begun 2 months before the onset of lichenoid eruption was stopped by the patient following the appearence of blisters. Examination revealed lichenoid plaques on the face, neck, trunk and extremities and tense bullae on the neck and extremities ( Fig. 1a ). The bullae were either on lichenoid plaques or normal appearing skin. Some of the blisters were hemorrhagic. Two skin biopsies were performed. The first biopsy from a blister with a lichenoid base on the arm, showed typical changes of lichen planus (LP) with subepidermal cleft formation. The second biopsy from a blister on normal appearing skin on the trunk showed subepidermal bulla with perivascular inflammatory cell infiltrate of eosinophils and lymphocytes. Direct immunofluorescence (DIF) of perilesional skin showed linear deposition of IgG and C3 along basal membrane zone (BMZ). Direct immunofluorescence on salt‐split skin revealed epidermal binding of immunoreactants. Indirect immunofluorescence showed a circulating IgG autoantibody binding to the BMZ at a titre of 1/200. Immunoblot analysis of her serum recognized minor 180 Kd BP antigen. An initial trial of dapsone (100 mg/day) for 2 weeks was not effective. She was then treated with oral methylprednisolone (32 mg/day), which induced rapid improvement in her skin lesions ( Fig. 1b ). After 2 months of treatment, corticosteroid was stopped and the patient stayed in remission for 1 year till she died due to myocard infarction.

Figure 1 Open in figure viewer PowerPoint (a) Lichenoid papules and hemorrhagic blisters on the face and the neck. (b) After 2 months of oral methylprednisolone therapy     

Perforation of large and small bowel in Henoch-Schonlein purpura

A 43-year-old woman with an unremarkable medical history was admitted with severe polyarthralgia, purpuric papules on her lower legs (Fig. 1), and recent pain with blue discoloration of her third left finger. She was taking no medication. At the time of presentation the abdominal examination was normal. Laboratory evaluation showed normal or negative values of BUN, creatinine, AST, WBC, Hb, VDRL, rheumatoid factor, HBSAg, ANA, ASO, cryoglobulins, cryofibrinogen, anticardiolipins, anti-Sm, anti-RNP, anti-Ro, anti-La, anti-SCl70, and anti-centromere. Hepatitis C titer was not obtained. Sedimentation rate was 61 mm/h and immune circulating complexes were present (14.2 <1.5μg/ml); normal, <1.5 μg/ml). Urine sediment analysis revealed the presence of cellular, hyalin, granular, and erythrocyteic casts. IgA level was 1.98 g/l (normal, 0.5–3.0 g/l). Skin biopsy showed extensive leucocytoclastic vasculitis. Deposits of IgA, IgM, and C3 were observed in the dermal vessels under direct immunofluorescence microscopy.
The patient was put on prednisone 60 mg/day. Three days after admission she complained of acute abdominal pain. Increased abdominal tenderness was noted on examination. An abdominal angiogram was normal. Because of the deteriorating intestinal condition, she received methylprednisolone 1 g IV per day. Despite this treatment she developed acute peritonitis 2 days later. Laparotomy disclosed three perforations on the caecum and ascending colon, and one on the ileum. She underwent sub-total colectomy with terminal ileostomy. Following surgery she was kept on parenteral methylprednisolone 1 g daily; cyclophosphamide 300 mg daily was started with progressive improvement of her condition.
The histopathologic examination of the colonic segment disclosed vasculitis of the medium-sized vessels (Fig. 2). Direct immunofluorescence microscopy revealed strong deposits of IgA and C3 in the vessel walls of the large intestine (Fig, 3).     

Scar sarcoidosis after hyaluronic acid injection

A 54-year-old woman presented with a 5-month history of tender nodules in both nasolabial folds that had developed 4 months after the injection of hyaluronic acid (HA) (Restylane) for wrinkles. The patient was treated with 1.5 mg/day betamethasone for 6 days and her lesions disappeared within 1 week. About 8 days after stopping therapy, however, new nodules developed at the same site, on previously healthy buttocks, and on old scars. On examination, nodules of about 0.5-1 cm in size were palpable at the nasolabial folds, and red nodules were present on the buttocks (Fig. 1) and on two old scars. Laboratory tests disclosed an increased protein C reaction (7.9 mg/L; normal value, < 5 mg/L) and acetyl-converting enzyme test (14.5 U/L; normal value, < 9 U/L). A chest X-ray was normal. Lung function tests showed a decreased lung CO diffusion, and chest axial tomography disclosed fibrosis, increased parenchyma density, and calcifications, findings suggestive of a diagnosis of lung sarcoidosis. An X-ray of the hands showed some bone cysts. Interestingly, two granulomatous lesions were observed at the sites of venipuncture. Histology of a gluteal lesion biopsy showed a deep granuloma with epithelioid and Langhans cells in the absence of necrobiosis. Sarcoidosis was diagnosed and the patient was given 50 mg/day prednisone with clear clinical improvement of cutaneous lesions in about 6 months. Decreased parenchyma density was also observed by chest axial tomography.     

Lichen sclerosus et atrophicus in sclerodermatous chronic graft-versus-host disease

In May 1994, a 40-year-old woman with chronic myeloid leukemia received an allogeneic bone marrow transplant (BMT) from her human leukocyte antigen (HLA) identical sister, after a conditioning regimen with cyclophosphamide and busulfan. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine (CsA) and methotrexate. Facial and palmoplantar erythema and moderate cholestasis developed on day 14 after the BMT. A diagnosis of acute GVHD was made and she was successfully treated with low doses of corticosteroids. On day 150 after the BMT, despite the prophylactic treatment of GVHD with CsA (150 mg/12 h), she developed several burning white plaque-like striae over the buccal mucosa and numerous itching violaceous lichenoid papules on the fingertips. Biopsy specimens obtained from both the skin of the fingertips and the oral mucosa ( Fig. 1 ) revealed patchy to diffuse subepithelial lymphocytic inflammation and necrosis of individual squamous cells, consistent with a diagnosis of chronic lichenoid GVHD. Despite therapy with CsA, topical and systemic corticosteroids (prednisone 60 mg/24 h), the oral lichenoid lesions persisted. On day 750 after the BMT, 2 months after withdrawal of immunosuppressive therapy, she developed several erythematous, pruriginous, and slight indurated lesions over the neck. These lesions coalesced into plaques, adopting a white atrophic-like appearance with follicular plugs similar to lichen sclerosus et atrophicus ( Fig. 2 ). Histopathologic examination showed hyperkeratosis with follicular plugging, atrophy of the stratum Malpighii with hydropic degeneration of the basal cells, homogenization of the collagen, incontinence of the pigment, and a discrete lymphoplasmocytic inflammatory infiltrate in the upper dermis ( Fig. 3 ). Systemic corticosteroid therapy was re-introduced. On day 850 after the BMT, physical examination revealed patchy hyperpigmentation affecting the back and limbs, and diffuse thickening and hardening of the skin of the legs, forearms, and dorsa of the hands, resulting in

Figure 1 Open in figure viewer PowerPoint Diffuse subepithelial lymphocytic inflammation and satellite cell necrosis of squamous cells in oral mucosa (hematoxylin and eosin, ×25)     

Cutaneous alternariosis in a patient with idiopathic pulmonary fibrosis

A 78-year-old farmer presented with symptomless skin lesions for evaluation. Two years prior, he had developed idiopathic pulmonary fibrosis (IPF) and had been treated thereafter with oral prednisolone 20 mg/day and occasionally with colchicine 1 mg/day. On examination, erythematoviolaceous, slightly infiltrated plaques, measuring approximately 5 x 9 cm, rubbery in consistency, intermingled with pustules, sometimes eroded, with distinctive borders, were noted on the dorsum of both hands and on the extensor surface of both forearms. The lesions had developed over a 20-day period. The skin of these areas was atrophic or eroded with multiple ecchymoses (Fig. 1). The abnormal laboratory findings included an elevated white blood cell count of 17,100/mm3, with 79% neutrophils, 16% lymphocytes, and 5% monocytes, C-reactive protein of 33.15 mg/dL (normal, <0.8 mg/dL), and immunoglobulin G of 598 mg/dL (normal, 701-1545 mg/dL). Other blood and urine tests performed were within normal limits. The diagnosis of IPF was reconfirmed through radiology, high-resolution computed tomography, and spirometry, as well as bronchoscopy and bronchoalveolar lavage fluid analysis. Coexistence of presumptive pulmonary alternariosis was excluded. Hematoxylin and eosin stained sections of the excised cutaneous specimen showed focal ulceration of the epidermis adjacent to a mainly intradermal abscess cavity. Within the latter, remnants of a partly destroyed hair follicle were seen amongst degenerating polymorphonuclear leukocytes, as well as many histiocytes and a few Langhans-type multinucleated giant cells. Minute collections of polymorphonuclear leukocytes were seen in the adjacent epidermis. Periodic acid-Schiff (PAS) and Gomori's silver methenamine stains showed a multitude of broad branching fungal hyphae and large spores within the aforementioned cavity, both free and within the cytoplasm of giant cells (Fig. 2). Immunohistochemistry was performed by means of the alkaline phosphatase anti-alkaline phosphatase (APAAP) method. Sections showed that the infiltrate consisted of an almost equal number of B and T lymphocytes, whereas histiocytes and the few giant cells were labeled with anti-CD68 antibodies. Skin smears and biopsy specimens taken twice from all lesions were used for mycologic examination. Wet mounts revealed numerous, brownish, septate hyphae and ovoid Skin smears and biopsy specimens taken twice from all lesions were used for mycologic examination. Wet mounts revealed numerous, brownish, septate hyphae and ovoid structures. Biopsy material was plated on Sabourand's dextrose agar with cloramphenicol (0.05 mg/mL). After 7 days at 27 degrees C, dark, gray-white colonies with a dark brown underside appeared. Microscopic examination of the colonies revealed hyphae with typical conidia having transverse and longitudinal septa. Based on macroscopic and microscopic examination, the isolates were identified as Alternaria alternata (Fig. 3). Treatment with prednisolone was reduced to 10 mg/day and the patient received oral itraconazole (200 mg/day). This resulted in progressive improvement of alternariosis, and the lesions healed completely within 3 months, when treatment was interrupted. Two years later, there is no evidence of recurrence.