Acrokeratosis neoplastica (Bazex syndrome): Report of two cases and literature review.

The skin often reflects the presence of internal diseases. Acrokeratosis neoplastica (Bazex syndrome) is a unique skin manifestation characterized by its erythematous hyperkeratosis with yellowish, adherent scales on the palm, sole, or other acral locations. There is a potentially high association between Bazex syndrome and malignant pathology, especially squamous cell carcinomas (SCC). To date, various skin conditions have been recognized as diagnostic indicators of insidious malignancies. The recognition of paraneoplastic dermatoses has a strong potential for prompt cancer detection and early therapeutic intervention. Here we describe clinical and forensic cases of Bazex syndrome that are associated with SCC of the glottis and lung. Bazex syndrome has been reported to be associated with a variety of cancers in addition to SCC. We review the clinical manifestations of Bazex syndrome and include updated knowledge on disease pathogenesis.

Deck-chair sign as a diagnostic clue for insidious T-cell lymphoma: An autopsy case of mycosis fungoides.

Skin reflects the presence of systemic diseases, leading to an unexpected diagnosis of insidious diseases. Deck-chair sign is a unique skin eruption characterized by widespread erythematous papules that become erythrodermic with spare skin folds. An association between the deck-chair sign and malignancies, especially hematological neoplasms, has been suggested. We report a forensic case of mycosis fungoides unexpectedly diagnosed in the presence of a deck-chair sign. Mycosis fungoides is representative of cutaneous T-cell lymphomas. Here, we successfully demonstrated the feasibility of analyzing mycosis fungoides in a forensic autopsy case using basic histopathology and serology. We emphasize that the underlying malignancy should be primarily considered in cadavers with a positive deck-chair sign and review current reports about this characteristic skin manifestation.

Malignancy-related Hypercalcemia Caused by Metameric Cutaneous Metastasis of Parathyroid Hormone-related Protein-producing Bladder Carcinoma with Squamous Cell Differentiation: An Autopsy Case of Cobb Syndrome.

A 74-year-old woman was admitted with hypercalcemia and prolonged disturbance of consciousness. The left buttock to the anterior aspect of the left thigh was swollen and erythematous, with a collection of 1.0-cm large, firm, elastic nodules distributed in a zosteriform pattern in the L1-L4 region. Based on autopsy findings, a very rare case of Cobb syndrome was diagnosed due to a spinal vascular malformation at the Th12-L4 level and L5 vertebral hemangioma. Cobb syndrome-associated cutaneous metastasis extending along the same metamere was complicated by immunohistochemically proven parathyroid hormone-related protein-producing advanced bladder carcinoma in this case.

Symmetrical Skin Lesions on the Gluteal Region in a Patient with Anti-Laminin-332 Mucous Membrane Pemphigoid.

Mucous membrane pemphigoid (MMP), previously called cicatricial pemphigoid, is a rare subepidermal immunobullous disorder that primarily affects the mucous membranes (1,2). MMP is divided into two major subtypes, anti-BP180-type MMP and anti-laminin-332 (previously called laminin 5 or epiligrin) MMP. Anti-laminin-332 MMP is known to be associated with malignant tumors (3), which may cause overexpression of autoantibodies and induce autoimmunity to laminin-332 (4). MMP primarily affects the mucous membranes, and widespread skin lesions are rare. In MMP, circumscribed skin lesions have been previously reported as occurring on the head, neck, and upper trunk (5). We report a case of anti-laminin-332 MMP presenting with symmetrical skin lesions characteristic of MMP on the weight-bearing areas of the gluteal region. A 66-year-old Japanese man presented with a month-long history of multiple erosions and blisters on the mucous membranes and skin, with conjunctival hyperemia, nasal obstruction, oral pain, and hoarseness of voice. Three days before the first visit, he was diagnosed with gastric cancer with liver metastasis by gastrointestinal endoscopy and abdominal ultrasound examination for tarry stool. Physical examination demonstrated erosions and tense bullae on the conjunctivae, tongue, and lips (Figure 1, a,b), as well as erosive erythematous skin lesions on the nape, right index finger, both legs, and symmetric lesions on the gluteal region (Figure 1, c). His body weight was 86 kg. Laboratory examinations showed slight liver dysfunction and elevation of C-reactive protein levels. Histopathologic examination of the skin lesions demonstrated subepidermal blisters with lymphocytic and eosinophilic infiltrates (Figure 1, d,e). Direct immunofluorescence (IF) revealed linear deposits of IgG and C3, but not IgA, along the basement membrane zone (BMZ) (Figure 1, f,g). An IgG subclass study showed IgG1 and IgG4 deposits. Indirect IF on normal human skin revealed weak positivity for IgA anti-keratinocyte cell surface antibodies and IgG anti-BMZ antibodies, which were bound to the dermal side of 1 mol/L NaCl-split skin (Figure 1, h). IgG immunoblot analyses of both normal human epidermal and dermal extracts showed negative results (including BP230, BP180, 290 kDa type VII collagen, and 200 kDa laminin-γ1). Immunoprecipitation using radio-labeled cultured keratinocyte lysate demonstrated positive reactivity with laminin-332 (Figure 1, i). We established the diagnosis of anti-laminin-332 MMP. We started treatment with oral minocycline (200 mg/day) and niacinamide (900 mg/day) with topical corticosteroids without any effect after 2 weeks of therapy. Administration of oral prednisolone (40 mg/day) with topical corticosteroids and alprostadil ointment on the skin lesions, as well as beclometasone dipropionate powder on the oral lesions resulted in significant improvement of mucocutaneous lesions within 10 days. Although the gastric cancer and liver metastasis initially responded to chemotherapy with fluorouracil and cisplatin, the patient succumbed to multiple organ failure 9 months after the initial visit. Anti-laminin-332 antibodies were originally detected by immunoprecipitation, as in our case. Immunoblotting of purified human laminin-332 have been subsequently developed, which detects the 165/145 kDa α3, 140 kDa ß3, and 105 kDa γ2 subunits of laminin-332 in various patterns (6). Today, the ELISA system uses laminin-332 preparations as adjunct diagnostic tools in MMP (7). Occasionally, a wide spectrum of autoantibodies is detected in MMP, for example, MMP with IgG antibodies to both BP180 and laminin-332, which were considered to be developed via epitope spreading. Detection of circulating IgA autoantibodies against the skin have also been reported in MMP (8). However, the pathogenic significance and mechanisms of coexistence of IgG anti-laminin-332 antibodies and IgA anti-keratinocyte cell surface antibodies found in our case are currently unknown. It is generally considered that IgG1 antibodies activate complements and are pathogenic in MMP, while IgG4 antibodies behave as blocking antibodies and are protective. In our case, direct IF revealed IgG1 and IgG4 deposits; the same was reported in a previous case report (9). The pathogenic roles of autoantibodies with different IgG subclasses need to be analyzed in further studies. Conjunctival mucosal lesions in MMP may occur by rubbing of the eyes due to irritation. Blinking subjects the conjunctivae to repeated friction. Vocal cords vibrate during breathing and speaking. The tongue moves while eating and drinking; in particular, the tip of the tongue gets into frequent contact with the inner sides of the incisor teeth. In the present case, characteristic symmetrical skin lesions were seen on the weight-bearing areas of the gluteal region on bony prominences which receive mechanical stresses in the sitting position. These skin lesions were subjected to repeated stretch and pressure stresses, but no ischemic changes were observed, such as decubitus ulcers. Therefore, the symmetrical skin lesions in the gluteal region as well as the ocular and oral mucosal lesions seen in our patient might have resulted from the same mechanism of pathogenesis. We reported a case of anti-laminin-332 MMP presenting with symmetrical gluteal skin lesions, probably induced by mechanical stress. MMP primarily affects the mucous membranes, and widespread skin lesions are rare. Our case emphasizes that clinicians need to specifically check for the presence of skin lesions on weight-bearing parts of the body during examination of patients with suspected MMP.

Management of Infected Calcific Myonecrosis: A Report of 2 Cases.

Calcific myonecrosis (CM) is a rare condition in which a large calcified mass develops after trauma. Generally, CM occurs in a lower extremity, and there have been no reports of its occurrence in the upper arm. We report 2 cases of infected CM, including a rare case of CM occurrence in the arm and a typical case in the leg. Case 1: An 84-year-old woman presented with a draining sinus and a large calcified mass in the arm and axillary region. The mass involved the neurovascular bundle; thus, complete resection was impossible. We performed surgical debridement and postoperative negative-pressure wound therapy with instillation and dwell. Case 2: A 43-year-old man presented with a large calcified mass in the right leg and 2 draining sinuses. After surgical debridement, negative-pressure wound therapy was initiated. However, the wound became infected, and we performed additional debridement, followed by a split thickness skin grafting. The infection was controlled in both patients, although complete resection was not feasible. Complete resection is generally considered the optimum treatment for infected CM, but it is difficult to achieve in some patients. Negative-pressure wound therapy with instillation and dwell appears as a good option for postoperative management if complete resection of infected CM cannot be achieved.

Advanced Lung Adenocarcinoma with Nivolumab-associated Dermatomyositis.

We herein report a 42-year-old man with advanced lung adenocarcinoma and nivolumab-associated dermatomyositis. Nivolumab, an anticancer drug that is classified as an immune checkpoint inhibitor, often induces immune-related adverse events (irAEs). However, there have so far been no reports regarding nivolumab-associated dermatomyositis. This patient was diagnosed with dermatomyositis due to the presence of proximal muscle weakness with abnormal electromyography and magnetic resonance imaging findings; skin lesions, such as heliotrope rash, shawl sign, and periungual erythema; and an elevated serum aldolase level after nivolumab administration. It is important to consider drug-associated dermatomyositis in the differential diagnosis of patients presenting with skin lesions and muscle weakness after nivolumab treatment.

Dipeptidyl peptidase-4 inhibitor-associated bullous pemphigoid in a patient with acquired reactive perforating collagenosis.

Bullous pemphigoid (BP) is a common autoimmune blistering disorder with unknown etiology. Recently, increasing numbers of BP cases which developed under the medication with dipeptidyl peptidase-4 inhibitors (DPP4i), widely used antihyperglycemic drugs, have been reported in published works. Here, we report a case of DPP4i (teneligliptin)-associated BP that developed in a 70-year-old Japanese man. Interestingly, the patient had acquired reactive perforating collagenosis (ARPC), which is also known to be associated with the onset of BP. In the present case, clinical, histopathological and immunological findings suggested that DPP4i rather than ARPC was associated with the onset of BP.

Possible paraneoplastic syndrome case of bullous pemphigoid with immunoglobulin G anti-BP180 C-terminal domain antibodies associated with psoriasis and primary macroglobulinemia.

A 61-year-old Japanese man developed bullous skin lesions during topical therapy for psoriasis vulgaris. Physical examination demonstrated numerous tense bullae and scaly erythemas on the trunk and extremities. Histopathology of the skin biopsy demonstrated subepidermal bullae and lymphocytic infiltration with eosinophils in the dermis. Direct immunofluorescence revealed linear deposits of immunoglobulin (Ig)G, IgA and C3 along the basement membrane zone. Indirect immunofluorescence of 1 mol/L NaCl-split skin showed IgG reactivity with both epidermal and the dermal sides. IgM reactivity with both the epidermal and dermal sides was also detected. Enzyme-linked immunosorbent assays showed negative results for both BP180 and BP230. Immunoelectrophoresis of serum and bone marrow aspiration revealed underlying primary macroglobulinemia with M-proteinemia of IgM-κ type. Immunoblot analysis revealed IgG, but not IgM, antibodies to recombinant protein of BP180 C-terminal domain. We diagnosed the present case as bullous pemphigoid with IgG anti-BP180 C-terminal domain autoantibodies associated with primary macroglobulinemia and psoriasis vulgaris. Systemic administration of prednisolone 30 mg/day resulted in dramatic improvement of both bullous and psoriatic skin lesions. When the bullous and psoriatic lesions relapsed, DRC chemotherapy (dexamethasone, rituximab and cyclophosphamide) for macroglobulinemia was performed. Then, the psoriatic lesions improved and the bullous lesions disappeared. We suggested that the present case may be paraneoplastic syndrome of bullous pemphigoid associated with primary macroglobulinemia and psoriasis vulgaris.

Disseminated extrafacial rosacea with papulonecrotic lesions.

BACKGROUND: Rosacea is a common skin disease and predominantly affects on the face of middle-aged women. It exceptionally occurs on the extrafacial areas such as ear, neck, axilla, and upper extremities, and has been reported as disseminated rosacea. MAIN OBSERVATION: A 40-year-old Japanese female presented with one-month history of erythematous skin eruption with burning sensation on the face, neck, and upper limbs. Physical examination showed rosacea-like eruption on the face as well as multiple papules disseminated on the neck, forearms, and hands. These extrafacial lesions demonstrated papulonecrotic appearance. Bilateral conjunctiva showed marked hyperemic which was consistent with ocular rosacea. Corneal opacity was also seen. Histology of the umbilicated papule on the neck revealed necrobiotic granulomas around the hair follicle with transepidermal elimination. Another tiny solid papule on the forearm suggesting early lesion also demonstrated necrobiosis with palisading granuloma but no transepidermal elimination. Systemic administration of minocycline and topical tacrolimus therapy promptly improved the skin lesions. Topical application of fluorometholone in temporary addition with levofloxacin improved ocular involvement 12 weeks after her 1st visit. The clinical course of the skin lesion and ocular symptoms mostly correlated. Then, the skin lesion and ocular symptoms often relapsed. Rosacea uncommonly associates with the extrafacial involvement as disseminated rosacea. The present case is characterized by the disseminated papulonecrotic lesions of the extrafacial areas histologically showing transepidermal elimination of necrobiotic granulomas. CONCLUSIONS: Dermatologists should recognize that papulonecrotic lesions of the neck and upper extremities might be extrafacial rosacea when the patient has rosacea on the face.

Cheek and periorbital peculiar discoid lupus erythematosus: rare clinical presentation mimicking tinea faciei, cutaneous granulomatous disease or blepharitis.

We present clinically peculiar facial discoid lupus erythematosus (DLE) that mimicked tinea faciei. Although DLE is a chronic autoimmune dermatosis, it has a variety of rare clinical presentations, including periorbital DLE, comedonic DLE and hypertrophic DLE recently. In this case, a scaly, erythematous lesion on the eyelid and the central healed, mildly elevated, annularly distributed facial DLE mimicked tinea faciei, complicating our diagnosis.