Yi-Ju Chen

Paraneoplastic pemphigus as the first manifestation of follicular dendritic cell sarcoma

Paraneoplastic pemphigus (PNP) is a life-threatening autoimmune bullous disease characterized by severe intractable mucositis and polymorphous skin eruptions [1]. The condition is associated mostly with hematological malignancies and less commonly with solid non-hematological neoplasms [1–3]. In about one-third of patients, there is no known underlying malignancy at the time of initial mucocutaneous Clinical Letter eruption [3]. Therefore, PNP can be a warning sign and an obligatory paraneoplastic marker for occult malignancy [4]. We describe a patient with PNP as the first manifestation of follicular dendritic cell sarcoma (FDCS). A 54-year-old woman previously in good health presented with painful erosions on the lips and oral mucosa for one month (Figure 1a), followed by erythematous to violaceous papules, vesicles and plaques on the face, trunk, limbs (Figure 1b) and palms (Figure 1c) for one week. Histopathology of the skin lesion revealed vacuolar interface change with necrotic keratinocytes and subepidermal bullous formation (Figure 1d). Direct immunofluorescence (DIF) was negative for IgG and complement. The clinicopathological features were compatible with erythema multiforme (EM). After initiation of systemic corticosteroids therapy, the cutaneous lesions showed slight improvement but the mucosal involvement persisted. The skin eruption became more

Flare-up of incontinentia pigmenti in association with Behçet disease.

A 16-year-old girl, who was diagnosed as having incontinentia pigmenti (IP) during infancy, presented with diffuse hyperpigmented patches along the lines of Blaschko over most of her body below the neck. She had no associated ocular or neurological abnormalities, but dental X-ray revealed congenital absence of one lower lateral and two upper lateral incisors. At the age of 7, she suffered from recurrent genital ulcers, oral aphthosis, and facial pustules. Pathergy test was positive. Behçet disease was diagnosed. After systemic corticosteroids were administered, her condition improved and remained stable for years. She experienced occasional flares of oral aphthous ulcers, but no recurrence of genital ulcers developed. Her mother and older sister had been diagnosed with IP, and her mother also had Behçet disease. She recently presented with itching, stinging erythematous patches with vesiculobullous lesions on previous hyperpigmented patches over her left calf. Genital ulcers and oral aphthous ulcers recurred simultaneously. There were no other infectious symptoms and signs over the upper respiratory tract and genitourinary tract. Routine laboratory tests revealed mild leukocytosis and elevated erythrocyte sedimentation Clinical Letter rate (113 mm/hr.). Blood chemistry, urinalysis, and antinuclear antibodies were within normal limits. The erythematous lesions disappeared quickly and turned to hyperkeratotic verrucous papules and vesicles (Figure 1a, b) within one week. Virus cultures for varicella-zoster virus and herpes simplex virus of lesional skin and bacterial cultures of blood and urine were negative. Histological examination showed marked hyperkeratosis, acanthosis, papillomatosis, and focal dyskeratosis of the epidermis (Figure 2a). The dyskeratotic cells were arranged in a whorled configuration (Figure 2b). The skin lesions resolved in ten days. The oral aphthous ulcers and genital ulcers healed two weeks later. Recurrent inflammation of incontinentia pigmenti associated with flare-up of Behçet disease was diagnosed. Incontinentia pigmenti is an X-linked dominant multisystemic syndrome with cutaneous, neurologic, dental, and ophthalmologic manifestations. Classically, there are four stages of cutaneous lesions: vesicular, verrucous, hyperpigmented, and hypopigmented. In recent studies, mutation in the gene NEMO (nuclear factor κB [NF-κB] essential modulator), also known as “the inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma”, on the X chromosome at Xq28, has been related to the development of incontinentia pigmenti [1, 2]. NF-κB may protect keratinocytes from tumor necrosis factor-α (TNF-α)-induced apoptosis [1, 2]. Epidermal cells with the mutant NEMO gene cannot activate NF-κB, so they will lose the ability to inhibit TNFα-induced apoptosis, giving rise to cutaneous lesions associated with IP [1, 2]. Most patients with IP remain stable after the initial inflammatory stage. However, some patients experienced episodes of late reactivation of the inflammatory cutaneous

Cutaneous granulomas in a patient with common variable immunodeficiency disease

A 43-year-old man presented to our dermatology department for evaluation of a plaque on his right shoulder. The lesion had first appeared six months earlier. The patient had a 20year history of common variable immunodeficiency disease (CVID) for which he had been on a monthly intravenous immunoglobulin (IVIG) regimen to maintain IgG levels above 650 mg/dL. Clinical examination showed a non-scaly, mildly pruritic, erythematous to yellowish indurated plaque in the right clavicular region, measuring approximately 2 cm x 1 cm (Figure 1). The patient denied any trauma, insect bites, or application of a topical agent. Laboratory findings were as follows: white blood cells 3,320/mL (41.6 % neutrophils and 43.1 % lymphocytes); hemoglobin10.4 g/dL; IgG: 716 mg/ dL (normal range: 650–1,600 mg/dL); IgM: < 1.09 mg/dL (normal range: 50–300 mg/dL); and IgA: < 10.46 mg/dL (normal range: 40–350 mg/dL). Liver and renal function tests, alkaline phosphate, and bilirubin were within normal limits. Serum calcium and phosphate levels as well as the erythrocyte sedimentation rate were likewise unremarkable. Antinuclear antibodies and rheumatoid factor were negative. A chest X-ray showed bilateral basal bronchiectasis; there was no evidence of nodules or hilar lymphadenopathy. Histology of a skin biopsy revealed non-caseating granulomatous inflammation in the dermis (Figure 2). Periodic acid-Schiff and acid-fast stains showed no microorganisms. Workup for sarcoidosis revealed no evidence of pulmonary, ocular, or articular involvement. Except for monthly IVIG therapy, the patient was on no other systemic medications such as systemic corticosteroids, hydroxychloroquine, or immunosuppressants. During one year of monthly follow-up, he developed no new granulomatous lesions, which led us to the diagnosis of cutaneous granulomas associated with CVID. Common variable immunodeficiency disease is a primary immunodeficiency disorder that may affect both adults and children. Table 1 shows the European Society of Primary Immunodeficiency Registry criteria for the diagnosis of CVID. Patients tend to develop recurrent infections, in particular respiratory and gastrointestinal infections caused by Streptococcus pneumoniae and Haemophilus influenzae [1]. Moreover, affected individuals are at greater risk for malignancies; the incidence of autoimmune diseases is also increased [2]. Histopathologically, patients frequently exhibit a variable spectrum of granulomatous changes without evidence of infection, including sarcoidal, caseating, or necrobiotic granulomas [3]. While there have been a few reported cases of cutaneous granulomas, usually located on the face and extremities, 5.4–22 % of CVID patients develop pulmonary, hepatic, splenic, or conjunctival granulomatous lesions [1]. Cutaneous as well as extracutaneous Figure 1 Erythematous to yellowish indurated plaque in the right clavicular region (arrow).