Pemphigus Vegetans of Hallopeau: A Case Report.

Dear Editor, Pemphigus vegetans (PV) of Hallopeau is a rare and indolent variant of pemphigus clinically characterized by vegetating lesions preceded by pustules mainly in flexural areas (1,2). This helps us to differentiate it from PV of Neumann, which is a more extensive and refractory disease, more alike to a pemphigus vulgaris outbreak with blisters which turn into vegetating plaques (3). We report the clinical presentation, course, and therapeutic response in a patient diagnosed with PV of Hallopeau from its early stage during a 3-year follow up. A 62-year-old man, non-smoker, presented at our clinic in July 2018 with hemorrhagic-serous crusts and fissures on the vermilion of the lower lip (Figure 1, a) and two merged circinate, sharply demarcated plaques on the right side of the groin (Figure 1, b). Plaque margins were elevated, with hypertrophic granulation tissue studded with pustules. Mucosal and cutaneous lesions persisted 6 and 4 weeks, respectively. The rest of the mucosa and skin were unaffected; the general state was good. The patient's family history for skin diseases was negative. The medical history included hypertension, atherosclerosis and hypercholesterolemia, hiatus hernia, and recent surgery (3 months prior) of an aortic abdominal aneurysm with reconstruction and synthetic graft placement. He was taking antihypertensives (fixed combination of 3 drugs, among them the ACE-inhibitor perindopril) with well-regulated blood pressure, statins, a pump-proton inhibitor, and acetylsalicylic acid. Differential blood count revealed eosinophilia. Histopathology finding showed acanthosis, suprabasal clefting with a suprabasilar bulla and acantholysis, prominent eosinophilic intraepidermal spongiosis, and heavy dermal infiltration of eosinophils and lymphocytes (Figure 2, a and b). The diagnosis of pemphigus was confirmed by direct immunofluorescence (DIF), which detected C3 deposits on the surface of keratinocytes throughout the epidermis of perilesional skin. Circulating pemphigus antibodies were detected by indirect IF. Only Dsg 3 antibodies were detected using an ELISA assay (233.23 RU/mL). After establishing the diagnosis of PV of Hallopeau, treatment with prednisolone 0.75 mg/kg/day orally in combination with adjuvant immunosuppression (azathioprine 100 mg daily) was started. Appropriate topical therapy with local steroids and antiseptic was applied. The steroid dose was titrated and gradually tapered down to the minimum required to control the disease - 10 mg. One-year remission was achieved. Azathioprine was withdrawn in October 2019 and since then the patient experienced a flare-up twice. The control of pemphigus flare-ups was achieved by a low dose of steroids (30 mg prednisolone orally). It remains debatable whether surgical trauma and radiology procedures such as angiographies (4) well as ACE-inhibitor drugs (5) triggered or aggravated the pemphigus. Early recognition and correct diagnosis of this rare type of pemphigus allows us to treat and control the disease successfully with lower doses of steroids, reducing complications to the minimum.

Grover's Disease in a Kidney Transplant Recipient.

Dear Editor, It is not unusual for patients with renal insufficiency to develop skin pathologies. There are reports in the literature of increased incidence of calciphylaxis, pruritus, perforating dermatoses, and porphyria cutanea tarda in this patient population (1). Although it is quite rare, Grover's disease (GD) has been reported in several patients with renal insufficiency, but only once in a renal transplant recipient (2). The disease follows three patterns: persistently pruritic, transient eruptive, or a chronic asymptomatic course (3). Common risk factors concomitant with disease prevalence are immunosuppression, HIV, hemodialysis, viral and bacterial infections, malignancies, and other skin pathologies like contact and atopic dermatitis (4). A 60-year-old woman had a family history of polycystic kidney disease and was subsequently diagnosed in 1997. The patient had concomitant hepatic involvement and a stable aneurysm of the anterior cerebral artery. Consequently, the patient preemptively received a kidney transplant in 2015. The immunosuppressive therapy consisted of tacrolimus, mycophenolate mofetil, and prednisone with basiliximab induction. In 2017, a biopsy of the right thigh demonstrated squamous cell carcinoma in situ measuring 1×1cm in size. The lesion was treated with surgical excision. The patient also exhibited an erythematous brown macule with undefined borders on the left side of the nose with a size of 12 mm; it was later determined to be actinic keratosis. The lesion was treated successfully with cryotherapy. During this period, a fever prompted a PCR for BK virus DNA which showed a substantial amount of copies, measuring 28,850 copies/mL in urine and 98 copies/mL in blood. The mycophenolate dose was reduced, and tacrolimus trough concentration was maintained at between 3 and 5 µg/L. In 2018 the patient presented with multiple pruritic erythematous papules located on the trunk. Upon histological biopsy, there was dominant suprabasal acantholysis with numerous cells separating from the epithelium. Furthermore, there was a moderate amount of mononuclear infiltrate in the upper portion of the dermis and sparse suprabasal clefts (Figure 1). Clinical presentation and histologic examination were consistent with Grover's disease. The patient was treated topically with betamethasone cream twice daily for four weeks. The skin changes persisted for only a few weeks. The pathophysiological mechanism causing GD is still unknown. It is usually only a transient skin condition that lasts no more than a few weeks, but there have been more chronic cases lasting for years, particularly in patients on hemodialysis (5). The lesions commonly affect the chest area but may spread to diffusely envelope the body as erythematous papules, pustules, lichenoid lesions, or vesicles (2). Grover characterized 4 different subtypes based on the pathohistological findings as Darier-like (the most common), pemphigus vulgaris-like, Hailey-Hailey-like, or spongiotic subtype (3). The histological patterns are not exclusive to one patient and may even be found concomitantly in a single lesion. The condition is definitively diagnosed through histology, showing distinctive acantholysis along the epidermis with dyskeratosis that is described as "corps ronds" and "grains" (3). Grover's disease is more prevalent in middle-aged Caucasian men than any other group, with a 1.6-2.1 gender ratio (6). It was originally thought that the disease was caused by dysfunctional eccrine sweat glands, as the ailment was more common in patients that had increased perspiration either due to environmental heat, fever, or extensive bedrest. This idea was reinforced by histological evidence of atrophied sweat glands in uremic patients with renal insufficiency (7). Moreover, a case series and case report described remissions of GD in their patients on hemodialysis that received a renal transplant (5,8). However, subsequent studies have not supported an association with sweat dysfunction and disease development, while others have only managed to attribute sweat gland dysfunction as the primary trigger in 20-30% of cases (9). Conversely, cold dry air and xerosis cutis is thought to trigger the disease because it is four times more likely to be diagnosed in the winter months (10). Ultraviolet radiation has been identified as an exacerbating factor for GD, which could have been the trigger for onset of disease in our patient as demonstrated by her squamous cell carcinoma and actinic keratosis (11). Despite immunosuppression being a risk factor for GD, as shown by its association in patients with HIV, bone marrow transplantation, hemodialysis, and hematological malignancies, GD has been reported only once in the literature after a renal transplant (2,4). As our case, that patient developed GD a few years after transplant without an obvious trigger and the lesions appeared as red papules that were disseminated over the anterior thorax. Their patient's cutaneous lesion resolved spontaneously after 2 weeks and never returned in the 2.5-year follow-up period. Their patient has had two renal allografts over a 20 year timespan, while ours had had her graft for only two years. The immunosuppressive regimen was slightly different: cyclosporine, azathioprine, and methylprednisolone versus our combination of tacrolimus, mycophenolate mofetil, and prednisone. Grover's disease can be treated conservatively by avoiding risk factors such as UV light and sweating as well as and applying moisturizing emollients which may cause the lesion to resolve spontaneously. Medical therapy consists of topic corticosteroids, topical vitamin D analogues, oral retinoids, and oral corticosteroids, PUVA, and methotrexate for resistant cases (6,12). When a patient exhibits pruritic papules of the skin, GD should be considered in differential diagnosis, especially in kidney transplant patients and those on hemodialysis. While the condition is rare, increased recognition in this patient population will allow for studies to further characterize this poorly understood disease.

A Giant Basal Cell Carcinoma Misdiagnosed and Mistreated as a Chronic Venous Ulcer.

Basal cell carcinoma (BCC) is the most common cutaneous malignancy. Giant BCCs are quite rare. They can cause extensive local invasion, disfigurement, and metastasis. We present a case of a 58-year-old woman with an unrecognized and inadequately treated ulcerated giant BCC sized 12.5 × 10.0 cm that occurred on her left lower leg without any sign of metastasis. Neglect and inadequate treatment of the primary lesion are the most important contributing factors responsible for size in giant BCC.

Nodular Prurigo Associated with Mycosis Fungoides - Case Report.

Mycosis fungoides (MF) is the most common type of cutaneous lymphoma and accounts for approximately 50% of all lymphomas arising primarily in the skin. The three types of MF lesions are patches, plaques, and tumors, according to which the disease is traditionally divided into three clinical stages. The clinical course can be protracted and take years or decades. In the final stage, MF evolves to a systemic form of the disease. Nodular prurigo (NP) is still a condition of unknown etiology characterized by papulonodular eruption and intense pruritus. Multiple diseases, including dermatological, systemic, and psychiatric diseases, have been assumed to cause NP. Pruritic skin lesions have been known to precede clinically evident B and T cell lymphomas for years. In the literature, pruritus and NP have been reported in patients affected by systemic Hodgkin and non-Hodgkin lymphomas. Only two cases of cutaneous lymphoma as underlying disease in patients with PN have been reported in the literature. We report a rare case of a patient with concomitant non-Hodgkin skin lymphoma - MF and NP. Our female patient with a 10-year history of MF stage IIb during the last three years had been presenting for regular check-up with itchy, newly formed, rarely disseminated nodules 5-8 mm in diameter on the forearms and lower legs. Sharply limited erythematosquamous, slightly infiltrated foci (as part of MF as the underlying disease) were visible on the trunk and extremities. Extracutaneous involvement of MF was excluded. We performed a biopsy on a nodule from the lower leg to rule out tumor stage MF; the biopsy confirmed NP. We conclude that prurigo nodules should not be confused with tumor stage MF. NP is a therapeutic challenge for any dermatologist. Any underlying diseases should be treated first.

Radiotherapy of primary cutaneous follicle center lymphoma: case report and review of literature.

Primary cutaneous follicle center lymphoma is an indolent primary cutaneous B-cell lymphoma originating from the follicle center cells, composed of a combination of centrocytes (small and large cleaved cells) and centroblasts (large noncleaved cells) with a follicular, follicular/diffuse, or diffuse growth pattern. Lesions are mostly located on the head, neck and trunk. A case is presented of a 56-year-old male patient with primary cutaneous follicle center lymphoma, with lesions involving the skin of the back, shoulders, presternal area and right forearm. As the patient presented a disseminated cutaneous form of the disease that involved several anatomical regions, complete work-up was followed by superficial fractionated radiotherapy of eight fields in VI expositions, with total irradiation dose of 1400 cGy upon the following fields: right and left pectoral region, left and right shoulders, right suprascapular region, and proximal third of the right forearm. Total irradiation dose applied upon each field for the lesions located on the left and right side of the back was 1500 cGy. This therapy resulted in significant reduction of visible tumor. The patient was regularly followed up on outpatient basis for 12 months of radiotherapy, being free from local recurrence and systemic spread of the disease.

Macular amyloidosis: a case report.

Macular amyloidosis is a major cause of skin pigmentation and a rare form of localized primary cutaneous amyloidosis in western countries, with a higher prevalence in Asia and South America. The etiopathogenesis of macular amyloidosis has not yet been fully clarified; a number of risk factors are involved, among them chronic friction in particular. A 54-year-old patient with macular amyloidosis is presented. The diagnosis of macular amyloidosis was based on history data on long-term persistence of the disorder, localized pruritus and constant scratching urge, grayish-brown pigmentation over the scapula, and detection of amyloid in histologic slides. Three-month tretinoin therapy resulted in pruritus alleviation, with no change in the appearance of hyperpigmentation. The exact incidence of macular amyloidosis in Croatia is not known, however, the issue appears to be underestimated or neglected in dermatology routine.

An unusual case of superficial lymphangioma of the right foot.

Superficial lymphangioma is a microcytic lymphatic malformation that is usually present already at birth. Women are more commonly affected than men are. It occurs because of the deep lymphatic circulation obstruction. Superficial lymphangioma is most commonly found in the mouth, especially the tongue, on the shoulders, neck, limbs, armpits and groin. It appears as a cluster of small firm blisters filled with clear or hemorrhagic lymph fluid, resembling frogspawn. We are presenting an unusual case of superficial lymphangioma of the right foot in an adult female patient.

Löfgren's syndrome presenting with erythema nodosum-like eruption.

Löfgren's syndrome is an acute form of sarcoidosis that mostly presents with erythema nodosum, periarticular ankle inflammation, arthritis, conjunctivitis, and unilateral or bilateral hilar or right paratracheal lymphadenopathy. Erythema nodosum is the most common cutaneous lesion in acute sarcoidosis, but it is histologically nonspecific, as it does not reveal sarcoidal granulomas upon microscopic examination. We present a case of a 57-year-old woman with acute onset of tender erythematous nodules on the calves, which were clinically erythema nodosum-like lesions. Histologic analysis revealed sarcoidal granulomas located in the dermis and subcutaneous tissue. Upon further work-up, the patient was found to have both pulmonary and ocular sarcoidosis. Based on this case, we recommend that all patients with erythema nodosum-like lesions undergo biopsy and further work-up for sarcoidosis is recommended in case of biopsy proven sarcoidal granulomas.

[Leukocytoclastic vasculitis in primary Sjögren syndrome: a case report]. / Leukocitoklasticki vaskulitis u primarnome sjögrenovu sindromu: prikaz bolesnika.

We report a case of primary Sjögren's syndrome (SSjö with cutaneous leukocytoclastic vasculitis. The accurate diagnosis of SSjö was established based on objective signs and symptoms of ocular and oral dryness and characteristic appearance of a biopsy sample from a minor salivary gland, and presence of anti-SS-A autoantibody. Another autoimmune disorder was not present, so diagnosis of primary SSjö was established. Histologic finding of skin biopsy of purpuric lesion was typical for leukocytoclastic vasculitis. The patient was treated with small doses of glucocorticoids and with local symptomatic therapy for ocular and oral dryness. SSjö is one of the most common autoimmune disorders and vasculitis is one of the most characteristic extraglandular manifestations, but wide spectrum of cutaneous involvement in primary SSjö has been little studied.

Folliculotropic mycosis fungoides with follicular mucinosis--case report.

Reports on clinical and histologic follicular alterations in patients previously diagnosed with mycosis fungoides (MF) or at the time of MF diagnosis are rare. The clinical and histologic criteria to distinguish MF associated with follicular mucinosis from follicular MF are a matter of debate. A patient is described with advanced clinical and histologic alterations predominated by follicular lesions and presence of mucin. In the early stage of the disease, folliculotropism was clinically and histologically present but less pronounced than epidermotropism and classic plaque-like lesions. The patient died four years after the diagnosis. As the term 'folliculotropic' describes a particular histopathologic finding, we consider it correct to use the term "folliculotropic MF" to denote atypical lymphocyte folliculotropism in the absence or presence of mild epidermotropism, presence of mucin, or no evidence for intrafollicular mucin. Folliculotropic MF seems to represent a specific clinicopathologic entity which may have a poorer prognosis than classic MF.

Atypical clinical appearance of pemphigus vulgaris on the face: case report.

Pemphigus vulgaris is an organ-specific autoimmune mucocutaneous disorder. In the majority of cases, the disease manifests initially with oral lesions, and may be limited to a single site for months before spreading. A 78-year-old woman with yellowish crusted areas on her left preauricular region and close to the medial angle of her right eye is presented. Although she described an episode of erosions on her lower lip, the involvement of mucosal surfaces was not noticed on examination. Before she presented to our Department, she was misdiagnosed as an actinic cheilitis and malignant skin tumor. Histopathologic examination and direct immunofluorescence confirmed the diagnosis of pemphigus vulgaris. Immunoblotting of epidermal extracts detected IgG antibodies against desmoglein 3 but not desmoglein 1, which was also confirmed by ELISA test. The patient responded favorably to systemic corticosteroid therapy combined with adjuvant immunosuppressive therapy, with complete clearance of the lesions.

A eleven-year retrospective study of metastatic carcinomas of the skin: own experience.

A brief overview of some metastatic carcinomas of the skin is given. The basic principles of the metastatic process, the distribution of metastases and clinical features of the most common metastatic carcinomas of the skin are presented, along with an account of our own data based on the records of Dermatohistology Registry of the University Department of Dermatology and Venereology, Zagreb University Hospital Center, for the 1994-2004 period and presentation of 22 cases of cutaneous metastases from this eleven-year period.

Primary anetoderma associated with antiphospholipid antibodies and micromorphologic vascular lesions: case report and literature review.

A 40-year-old male patient with primary anetoderma is presented in whom antiphospholipid antibodies were detected while not fulfilling diagnostic criteria for antiphospholipid syndrome. The possible pathogenic role of antiphospholipid antibodies in the disease development is postulated.

Cytokeratin 10 and Ki-67 nuclear marker expression in keratoacanthoma and squamous cell carcinoma.

The most frequent consideration in the clinical and histologic differential diagnosis of keratoacanthoma is squamous cell carcinoma. In the present study, cytokeratin 10 expression and proliferation rate as measured by Ki-67 expression were compared between 50 clinically and histologically diagnosed keratoacanthomas and 50 squamous cell carcinomas. Tissue sections from the skin were immunohistochemically stained with anti-cytokeratin 10 and anti-Ki-67 monoclonal antibodies. The distribution of cytokeratin 10 expression and proliferative cell count were analyzed. Study results showed higher cytokeratin 10 expression in keratoacanthomas than in squamous cell carcinomas and different distribution of staining in the two entities. The analysis of cytokeratin 10 expression showed a much wider range of values and statistically higher median (p<0.001) in keratoacanthomas than in squamous cell carcinomas. Additionally, the proliferation index of keratinocytes as measured by Ki-67 expression was significantly higher in squamous cell carcinomas than in keratoacanthomas (p<0.01). These results may prove helpful in histologic differentiation of these disorders.

Zoon plasma cell balanitis: an overview and role of histopathology.

Balanitis circumscripta plasmacellularis or Zoon's balanitis is an idiopathic, benign condition of the genitalia that mostly presents as a solitary, persistent plaque on the glans of primarily uncircumcised, middle-aged to older men. Its etiology and pathogenesis remains speculative. This article provides an overview of the clinical morphology, microscopic features, differential diagnosis and therapy. Particular attention is paid to histopathologic features. Besides, a case is presented of an uncircumcised man with clinical and histologic features of balanitis circumscripta plasmacellularis who was successfully cured by circumcision. The distinction of this lesion from similar lesions is rather important, and a large group of disorders such as premalignant, infective and other inflammatory penile diseases should be definitely taken into consideration on the differential diagnosis. It seems that circumcision might be the current 'gold standard' for treatment of this disorder.

Mal de Meleda: genetic haplotype analysis and clinicopathological findings in cases originating from the island of Mljet (Meleda), Croatia.

BACKGROUND: Mal de Meleda (keratoderma palmoplantaris transgrediens) is an autosomal recessive disorder, first described on the island of Mljet (Meleda), Croatia. The candidate region for the gene responsible for this disorder was found on the chromosome 8qter, and the responsible mutations have recently been identified in 12 Algerian and 7 Croatian families. OBJECTIVES: To fully characterize all 12 living cases originating from the original setting of the disease, the island of Mljet, in the light of new findings and using modern diagnostic technology. PATIENTS AND METHODS: Twelve patients and 37 family members were identified over the period 1998-1999, interviewed and examined. RESULTS: The reconstruction of 8 genealogies suggests a common ancestry of all cases but one. The clinical presentation and pathologic findings of these cases are described in detail and are consistent with previous reports. Symptoms and signs were found to be milder in non-manual workers who had applied continuous symptomatic treatment. Blood samples were taken from 8 cases and 16 close relatives for genetic studies. These confirmed a shared haplotype in all cases, but in none of 17 unaffected control individuals, near the marker D8S1751 on chromosome 8. CONCLUSIONS: This review characterizes mal de Meleda in its original setting and shows that the sporadic cases found in the regions of medieval trade routes of the Republic of Dubrovnik (Middle East and Northern Africa) carry the same mutation as the patients from Mljet Island, Croatia.