Positive Darier Research Articles

Urticaria Pigmentosa – A Case Report with a Review of the Literature

Mastocytosis encompasses a rare group of diseases characterized by the accumulation of mast cells, primarily in the skin or internal organs. In the 2016 revised WHO classification, mastocytosis is divided into cutaneous mastocytosis (CM), systemic mastocytosis (CM), and localized mast cell tumor. Cutaneous mastocytosis (CM) includes maculo-papular CM/urticaria pigmentosa (UP), diffuse CM and cutaneous mastocytoma. Urticaria pigmentosa is the most common skin variant. It presents with erythematous brownish macules or papules, often accompanied by pruritus. A case of a 48-year-old woman with disseminated, mildly pruritic, sharply demarcated, livid-brownish macules on the skin of the trunk and extremities is presented. A positive Darier symptom was established. Laboratory tests revealed granulocytosis (73%) and lymphocytosis (19.8%). Serum tryptase and 24-hour urine 5-hydroxyindoleacetic acid were not elevated. The diagnosis of urticaria pigmentosa was confirmed by the histopathological examination revealing perivascular infiltrates of mast cells, mainly in the deep dermis. Screening performed did not detect systemic involvement. Symptomatic treatment with H1 and H2 blockers and topical corticosteroid was carried out. Avoidance of triggers is recommended. The patient's condition has improved. Both a historical review of mastocytosis and a revised classification, as well as the epidemiology, etiology with triggering factors, clinical presentation, laboratory investigations, and management of urticaria pigmentosa are presented.

Diffuse Cutaneous Mastocytosis: A Current Understanding of a Rare Disease.

Mastocytosis is a heterogeneous disease characterized by the expansion and accumulation of neoplastic mast cells in various tissues. Diffuse cutaneous mastocytosis (DCM) is a rare and most severe form of cutaneous mastocytosis, which typically occurs in childhood. There have been reports of a familial DCM with specific gene mutations, indicating both sporadic and hereditary factors involved in its pathogenesis. DCM is associated with severe MC mediator-related symptoms and an increased risk of anaphylaxis. The diagnosis is based on the appearance of skin lesions, which typically show generalized thickening, erythroderma, blistering dermographism, and a positive Darier's sign. Recognition, particularly in infants, is challenging due to DCMs resemblance to other bullous skin disorders. Therefore, in unclear cases, a skin biopsy is crucial. Treatment focuses on symptom management, mainly including antihistamines and mast cell stabilizers. In extremely severe cases, systemic steroids, tyrosine kinase inhibitors, phototherapy, or omalizumab may be considered. Patients should be equipped with an adrenaline autoinjector. Herein, we conducted a comprehensive review of literature data on DCM since 1962, which could help to better understand both the management and prognosis of DCM, which depends on the severity of skin lesions, intensity of mediator-related symptoms, presence of anaphylaxis, and treatment response.

Challenges in the Diagnosis of Cutaneous Mastocytosis.

Mastocytosis is characterized by an accumulation of clonal mast cells (MCs) in tissues such as the skin. Skin lesions in mastocytosis may be clinically subtle or heterogeneous, and giving the correct diagnosis can be difficult. This study compiles personal experiences together with relevant literature, discussing possible obstacles encountered in diagnosing skin involvement in mastocytosis and cutaneous mastocytosis (CM). The nomenclature of the term "CM" is ambiguous. The WHO classification defines CM as mastocytosis solely present in the skin. However, the term is also used as a morphological description, e.g., in maculopapular cutaneous mastocytosis (MPCM). This is often seen in systemic, as well as cutaneous, mastocytosis. Typical CM manifestations (MPCM), including mastocytoma or diffuse cutaneous mastocytosis (DCM), all share a positive Darier's sign, and can thus be clinically recognized. Nevertheless, distinguishing monomorphic versus polymorphic MPCM may be challenging, even for experienced dermatologists. Less typical clinical presentations, such as MPCM with telangiectatic erythemas (formerly called telangiectasia macularis eruptiva perstans), confluent, nodular or xanthelasmoid variants may require a skin biopsy for histopathological confirmation. Because MC numbers in CM have a large overlap to those in healthy and inflamed skin, detailed histopathological criteria to diagnose mastocytosis in MPCM are needed and have been proposed. D816V KIT mutational analysis in tissue is helpful for confirming the diagnosis. Biomarkers allow the prediction of the course of CM into regression or evolution of the disease. Further diagnostic measures should screen for concomitant diseases, such as malignant melanoma, and for systemic involvement. Whereas in typical cases the diagnosis of CM may be uncomplicated, less typical manifestations may require specific investigations for making the diagnosis and predicting its course.

Current Challenges in the Diagnosis of Pediatric Cutaneous Mastocytosis

Pediatric mastocytosis is mostly a cutaneous disease classified as cutaneous mastocytosis (CM), which is characterized by mast cell (MCs) accumulation in the skin and the absence of extracutaneous involvement. Based on the morphology of skin lesions, CM can be divided into three major forms: maculopapular CM (MPCM), diffuse CM (DCM) and mastocytoma of the skin. A positive Darier’s sign is pathognomonic for all forms of CM. MPCM is the most common form, presenting with red-brown macules or slightly raised papules. Mastocytoma is characterized by solitary or a maximum of three nodular or plaque lesions. DCM is a rare, severe form which presents as erythroderma, pachydermia and blistering in the infantile period of the disease. CM is associated with MC mediator-related symptoms, most commonly including pruritus, flushing, blistering, diarrhea and cramping. Anaphylactic shock occurs rarely, mainly in patients with extensive skin lesions and a significantly elevated serum tryptase level. Childhood-onset MPCM and mastocytoma are usually benign diseases, associated with a tendency for spontaneous regression, while DCM is associated with severe mediator-related symptoms, an increased risk of anaphylaxis and, in some cases, underlying systemic mastocytosis (SM). In contrast to adults, SM is a rare finding in children, most commonly presenting as indolent SM. However, advanced SM sporadically occurs.

A rare case of cutaneous mastocytosis in pediatric practice

Mastocytosis belongs to a group of rare diseases in which there is a pathological accumulation of mast cells in tissues. In childhood, it is more often limited to skin lesions. A clinical case of a bullous form of severe cutaneous mastocytosis, with the onset of the disease at 3.5 months, is presented. Cutaneous manifestations with a positive Darier–Unna symptom and a high level of tryptase in the blood, the exclusion of systemic lesions allowed diagnosing cutaneous mastocytosis and choosing treatment tactics.

Anaphylaxis Accompanying Mastocytoma in Childhood: A Case Report

Background: Mastocytosis is a heterogenous disorder characterized by accumulation of mast cells in different tissues. Mastocytosis may be limited to skin or it may involve bone marrow, liver, spleen and lymphatic tissue as systemic mastocytosis. Patients may also present with anaphylaxis. Here we report a six-year-old boy with atopic dermatitis, wheat anaphylaxis, and solitary mastocytoma. Case report: The dermatologic manifestations of atopic dermatitis appeared early in his first days of life and were all over his face with a dark red infiltrate, edema, small vesicles and severe itching. At the age of 3 months, the patient was fed with an ordinary milk formula for the first time, which immediately resulted in severe vomiting, generalized urticaria and angioedema of the lips and eyes, followed by lethargy and atony. The result of RAST test indicated allergy to wheat and cow’s milk. At the age of two years, his mother noticed a rubber-like skin lesion on his left arm with positive Darier sign. Laboratory tests were all within normal limits except IgE and serum tryptase which were 1425 IU/mL and 31 ng/ml, respectively. Conclusion: To conclude, Anaphylaxis may accompany cutaneous forms of mastocytosis even mastocytoma. Delayed diagnosis due to the lack of awareness may lead to recurrent life-threatening events, particularly in infancy when anaphylactic reactions are easily misdiagnosed as infants are not capable of expressing their symptoms.

Mastocytosis in children: a single-center long-term follow-up study.

Mastocytosis is a heterogeneous group of rare disorders characterized by the accumulation of clonal mast cells in organs such as the skin and bone marrow. The diagnosis of cutaneous mastocytosis (CM) is based on clinical findings, positive Darier's sign, and histopathology, if necessary. Medical records of 86 children with CM diagnosed during a 35-year long period were reviewed. Most patients (93%) developed CM during the first year of life (median age 3 months). Clinical features at presentation and during the follow-up period were analyzed. Baseline serum tryptase level was measured in 28 patients. Atotalof85% of patients had maculopapular cutaneous mastocytosis/urticaria pigmentosa (MPCM/UP), 9% had mastocytoma, and 6% had diffuse cutaneous mastocytosis (DCM). Boy to girl ratio was 1.1:1. Fifty-fourof86 patients (63%) were followed from 2 to 37 years (median 13 years). Complete resolution was registered in 14% of mastocytoma cases, 14% of MCPM/UP, and in 25% of DCM patients. After the age of 18, skin lesion persisted in 14% mastocytoma, 7% MCPM/UP, and 25% children with DCM. Atopic dermatitis was diagnosed in 9.6% ofpatients with MPCM/UP. Threeof28 patients had elevated serum tryptase. Prognosis in all patients was good, and there were no signs of progression to systemic mastocytosis (SM). To the best of our knowledge, our results represent the longest single-center follow-up study of childhood-onset CM. We found no complications of massive mast cell degranulation or progression to SM.

Aggressive Systemic Mastocytosis with a Relatively Non-aggressive Course

Background: Mastocytosis is a heterogeneous group of disorders that is characterized by excessive proliferation and pathologic accumulation of mast cells in various body tissues. The mast cells also have abnormal morphology and aberrant expression of surface receptors. Clinical Description: A 4-year-old boy was brought with a history of generalized skin lesions since birth and abdominal distension for 3 years. The diagnosis had not been established to date. General physical examination revealed severe acute malnutrition, pallor, dental staining, facial hypertrichosis, polymorphous skin lesions (cicatricial alopecia, diffuse erythema, multiple plaques of variable diameter, skin-colored nodules, and hypertrophic irregular scars), and positive Darier's sign. He also had hepatosplenomegaly. The differentials considered were congenital erythropoietic porphyria, systemic mastocytosis (SM), multifocal Langerhans cell histiocytosis, and linear immunoglobulin A bullous dermatosis. The presence of mast cells on skin biopsy and elevated serum tryptase levels led us to suspect SM and perform bone marrow studies. The diagnosis of “aggressive” SM was initially made on the application of the diagnostic criteria but revised to “smoldering” SM with the emergence of Vitamin B12 deficiency as the probable cause of pancytopenia. Management: Management was planned by a multidisciplinary team: pediatrician, dermatologist, and hematopathologist. The parents were counseled about the nature, natural history, treatment options, and prognosis of the disorder. The child was provided with nutritional rehabilitation and medication for the cutaneous symptoms (selective histamine H1 receptor inverse agonist, H2-receptor antagonist, and application of topical tacrolimus and calamine lotion). Conclusion: The prognosis varies according to subtype. Careful correlation of clinical and laboratory investigations is required when applying the diagnostic criteria for staging.

Cutaneous Mastocytosis in an 8-year-old child: Case Report and Review of the Literature

Mastocytosis is a clinical condition occurring from birth to adulthood and may involve mainly the skin and/ or many organs such as the liver, bone marrow, spleen and lymph nodes. The condition has a bimodal distribution presenting in children from birth to 2 years of age and in patients older than 15. In adult patients may or may not have cutaneous involvement. In cutaneous mastocytosis the mast cells infiltrate mostly the skin but may be associated with systemic symptoms due to mast cell mediators release. In children, the disease manifests with one or more tan to red-brown papules or plaques (urticaria pigmentosa). Patients with mastocytosis may be asymptomatic or have symptoms due to mast cells degranulation – itch, flush, headache, syncope, gastrointestinal complaints of abdominal pain and diarrhea. A pathognomic sign for the disease is Darier`s sign where stroking of the skin lesions provokes pronounced urtication due to mast cells degranulation. Diagnosis of cutaneous mastocytosis is based on clinical morphology of skin lesions, positive Darier`s sign and histological skin lesions stained for tryptase and/or CD117. Therapeutic management involves avoiding triggers, H1-/H2- receptor blockers and symptomatic medications. All patients with cutaneous mastocytosis require follow-up examinations. Herein, a clinical case of an 8-year-old male patient with cutaneous mastocytosis is presented. An update comprehensive review of literature focusing on clinical findings, diagnosis and modern therapeutic modalities is highlighted.

Firm, enlarging papule on an infant's proximal thigh

Firm, enlarging papule on an infant's proximal thigh

Pediatric Leukemia Cutis: Darier’s Sign

Leukemia Cutis (LC) is defined as infiltration and proliferation of neoplastic cells of lymphoid or myeloid lineage in the epidermis, dermis or hipodermis. The case of a 7-month-old infant with Leukemia Cutis, characterized by papules, nodules with a positive Darier’s sign, with histopathological findings of an infiltrate of monomorphic lymphoid cells in the dermis and hypodermis, without the presence of mast cells, as a manifestation before acute lymphoblastic leukemia is presented in this article.

Mediator-Related Symptoms and Anaphylaxis in Children with Mastocytosis.

Mastocytosis is characterized by the pathological accumulation of mast cells (MC) in various organs. In these patients, MC may degranulate and thereby contribute to clinical symptoms, especially when a concomitant allergy is present. However, MC activation can not only be induced by high-affinity receptors for IgE, but also by anaphylatoxins, neuropeptides, IgG immune complexes, complement-components, drugs, products of bacteria or parasites, as well as physical factors such as heat, cold, vibration, stress, sun, or physical effort. Symptoms due to mediators released by activated MC may develop in adults suffering from systemic mastocytosis, but also evolve in children who usually have cutaneous mastocytosis (CM). Clinically, CM is otherwise characterized by typical brown, maculopapular skin lesions or mastocytoma associated with a positive Darier’s sign. Pruritus and flushing are common and blistering may also be recorded, especially in diffuse CM (DCM). Pediatric patients with mastocytosis may also have gastrointestinal, respiratory, and neurologic complaints. Although anaphylaxis is not a typical finding, pediatric patients with massive skin involvement and high tryptase levels have a relatively high risk to develop anaphylaxis. This paper reviews MC mediator-related symptoms and anaphylaxis in children with mastocytosis, with special emphasis on risk factors, triggers, and management.

Darier sign in a teenager with primary cutaneous marginal zone lymphoma.

Primary cutaneous marginal zone lymphoma (PCMZL) is a low-grade B-cell lymphoma that arises in the skin. An adolescent male presented with dermal nodules on the arms, legs, and back with a positive Darier sign, ultimately diagnosed as PCMZL. The nodules demonstrated a partial response to doxycycline in the setting of prior Lyme disease followed by a complete response to rituximab.

Co-Occurrence of neurofibromatosis-1 with urticaria pigmentosa: A Coincidental association?

Neurofibromatosis-1 (NF-1) is a neuroectodermal abnormality characterized by multiple neurofibromas, café-au-lait macules, axillary freckling, and Lisch nodules. Urticaria pigmentosa (UP) is a maculopapular cutaneous mastocytosis due to mast cell hyperplasia. We report a case of NF-1 associated with UP. A 19-year-old male presented with multiple neurofibromas, café-au-lait macules, axillary freckling, and Lisch nodules. He also had UP lesions with positive Darier's sign. A clinical diagnosis of NF-1 with UP was made and confirmed histopathologically. Mastocytosis exhibits mast cell hyperplasia due to C-kit gene mutation. Mast cell mediatiors directly contribute to neurofibroma growth. C-kit receptor abnormality is implicated in the formation of neurofibromas as well as in UP. With possible interconnected underlying pathology of mast cell hyperplasia and increased mast cell mediators in both UP and NF-1, a possible association of NF and UP beyond simple coincidence should be considered.

CUTANEOUS MASTOCYTOSIS IN THE ADULT: WHAT LIES BENEATH

Mastocytosis is a disorder characterized by clonal mast cell proliferation and accumulation within various organs, most commonly, the skin. Adult-onset mastocytosis is highly suggestive of a systemic involvement and the cases limited to the skin are uncommon. The authors report a 61-year-old male with pruritus associated with hyperpigmented maculopapular skin lesions and a positive Darier’s sign. The skin biopsy revealed spindle mast cells infiltrations. The bone marrow study was normal. He started on H1 antihistamines with significant clinical improvement

Childhood Solitary Cutaneous Mastocytoma: Clinical Manifestations, Diagnosis, Evaluation, and Management.

Background: The diagnosis of solitary cutaneous mastocytoma is mainly clinical, based on lesion morphology, the presence of a positive Darier sign, and the absence of systemic involve-ment. Knowledge of this condition is important so that an accurate diagnosis can be made.Objective: To familiarize physicians with the clinical manifestations, diagnosis, evaluation, and man-agement of a solitary cutaneous mastocytoma.Methods: A PubMed search was completed in Clinical Queries using the key term “solitary cutane-ous mastocytoma”. The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. Only papers published in English language were included. The information retrieved from the above search was used in the compilation of the present article.Results: Typically, a solitary cutaneous mastocytoma presents as an indurated, erythematous, yellow-brown or reddish-brown macule, papule, plaque or nodule, usually measuring up to 5 cm in diameter. The lesion often has a peau d'orange appearance and a leathery or rubbery consistency. A solitary cu-taneous mastocytoma may urticate spontaneously or when stroked or rubbed (Darier sign). Organo-megaly and lymphadenopathy are characteristically absent. The majority of patients with skin lesions that erupt within the first two years of life have spontaneous resolution of the lesions before puberty. Treatment is mainly symptomatic. Reassurance and avoidance of triggering factors suffice in most cases.Conclusion: The diagnosis is mainly clinical, based on the morphology of the lesion, the presence of a positive Darier sign, and the absence of systemic involvement. A skin biopsy is usually not neces-sary unless the diagnosis is in doubt.

Urticaria pigmentosa presenting as cardiac emergency

Abstract Introduction Urticaria pigmentosa is a common type of mastocytosis. It is a disease that needs to be treated by doctors of many specialties. Aim We present a case report based discussion concerning the approach to a patient with this disease including treatment, prophylaxis of degranulation and anesthesia in affected patients. Case study A 57-year-old male patient was admitted for diagnosis of maculopapular lesions that first occurred about 10 years before. He presented massive maculopapular lesion covering his trunk and legs with positive Darier's sign. The punch biopsy revealed mastocytosis, the tryptase level was slightly elevated – 22 μg/L ( N Results and discussion Patient was not diagnosed before although he had many serious symptoms of the disease which were ignored by both, doctors and the patient (fainting, the cardiorespiratory arrest and the seizures during the anesthesia, recurring diarrhea). After last incident, when the skin lesion was already covering almost whole trunk and legs he was sent to the Department of Dermatology for further diagnosis that was described in beginning. Conclusions Mastocytosis is a disease that is not easy to diagnose, classify and treat for doctors. But it is crucial that patients know the disease well and are informed on how to cope with the symptoms.

Solitary mastocytoma with positive Darier′s sign

A 15-month-old girl child presented with a 6-month-old solitary nodular lesion over her lower abdomen. No symptoms were reported by the parents, except for temporary redness and swelling of the lesion developing while manipulating. Systemic symptoms such as spontaneous hives, flushing, wheezing, unexplained diarrhea, or bone pains were absent. Cutaneous examination revealed a 2.5 × 1.5 cm sized firm, nontender, yellow-tan to light-brown noduloplaque with a characteristic “peau d’orange” surface and rubbery consistency [Figure 1]. Gentle stroking of the lesion evoked erythema and swelling within 30 seconds [Figure 2], which became pronounced in 2 minutes [Figure 3], signifying a positive Darier's sign. Systemic examination was unremarkable. Histopathology of the lesion revealed mast cell aggregates in the papillary dermis, which was confirmed on toluidine blue staining. A diagnosis of solitary mastocytoma was made. Parents were reassured about its benign nature and advised to avoid triggering factors such as rubbing the lesion.Figure 1: Yellow-tan to light-brown nodule over the right lower abdomen of a 15-month-old girl child, with an “orange peel” appearanceFigure 2: Appearance of lesional erythema and mild edema after 30 s of gentle stroking with a key in the center of the lesion (the vertical mark in the center being the site of strokingFigure 3: Pronounced lesional and perilesional erythema and edema within 2 min signifying a strongly positive Darier's signMastocytosis is characterized by abnormal proliferation of mast cells, involving only the skin (cutaneous mastocytosis or CM) or extracutaneous organs (systemic mastocytosis). Skin is the most commonly involved organ, especially in children. Solitary mastocytoma (SM), the second most common type of CM, accounts for 10%–15% of the total cases of CM.[1] The other variants of CM include urticaria pigmentosa (the most common variant), diffuse CM, and telangiectasia macularis eruptive perstans (TMEP). A mastocytoma is usually solitary that presents as a yellow to tan-brown nodule or plaque, ranging 0.5–3 cm in diameter. A shiny peau d’orange or “orange peel” appearance with a rubbery consistency is characteristic of a classical lesion. Common locations include the trunk, head and neck, and extremities. Although lesions may rarely appear in adulthood, majority present during infancy; with only 10% appearing after 2 years of age.[2] The lesions may be asymptomatic or become itchy and swollen on rubbing. The clinical differential diagnosis includes melanocytic naevi, xanthomas, and xanthogranulomas.[3] Darier's sign, named after the French dermatologist Ferdinand-Jean Darier, is considered to be a foretoken of CM. Gentle rubbing or stroking of lesions of cutaneous mastocytosis is followed by local itching, erythema, and weal formation within 2–5 min, which may last from 30 min to several hours. The pathophysiology of Darier's sign involves stroking-induced degranulation of the increased number of functionally normal dermal mast cells, followed by exocytosis of effector molecules such as histamine and heparin.[4] Of all the variants of CM, Darier's sign is most commonly encountered in urticaria pigmentosa, with up to 94% positivity reported in children with urticaria pigmentosa in a clinical analysis of 71 childhood cases with CM.[5] However, its positivity has been reported in only 50% cases of SM.[3] Intriguingly, Darier's sign has also been reported in conditions other than CM, such as leukemia cutis, juvenile xanthogranuloma, histiocytosis X, and rarely in cutaneous large T-cell lymphoma. Darier's sign needs to be severalized from Pseudo-Darier's sign, an augury of congenital smooth muscle hamartomas, characterized by transient piloerection and elevation or increased induration of the lesion induced by rubbing.[4] The diagnosis of SM is confirmed on lesional biopsy with histopathology revealing mast cell aggregates in the papillary dermis, confirmed by metachromatic stains such as toluidine blue. The condition is benign and self-limited, with systemic involvement being uncommon and spontaneous involution of the lesion expected by puberty, rendering laboratory evaluation de trop. Reassurance along with avoidance of triggering factors such as pressure, friction, and intake of mast cell degranulating agents (eg, aspirin) suffice in most cases. Medical treatment with antihistamines, topical or intralesional steroids, or topical tacrolimus is indicated in select cases.[23] Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Dermatoscopy in diagnosing maculopapular cutaneous mastocytosis

The diagnosis of cutaneous mastocytosis is based on the clinical finding of the pigmented macules or papules, positive Darier's sign and a dermal infiltrate composed of mast cells that can be better visualized by the use of special stains (Giemsa or Toluidine blue). Clinical, dermatoscopic and histopathological presentations of new appearing pigmented lesions in a female patient were presented. Dermatoscopic findings of pigment network-like structure combined with parallel pigmented lines and central reddish background in a adult patient with new appearing pigmented lesions should led us to searching for cutaneous mastocytosis.

Combined central xanthomatous and peripheral macular skin lesions in an infant

Combined central xanthomatous and peripheral macular skin lesions in an infant