Trichoscopy of Non-Cicatricial Alopecia.

MAIN FINDINGS

Alopecia areata
Micro-eclamation mark hairs, tapered hairs, black dots, yellow dots, upright regrowing hairs, pigtail regrowing hairs, vellus hairs and broken hairs.

Androgenetic alopecia
Increased proportion of thin and vellus hairs, hair shaft thickness heterogeneity, perifollicular discoloration (hiperpigmentation), and presence of variable number of yellow dots

Telogen effluvium
Upright regrowing hairs and predominance of hair follicle openings with only one emerging hair shaft.

Psoriasis 
Silver-white scales, red dots and globules, twisted red loops, and glomerular vessels.

Seborrheic dermatitis
Yellowish scales, arborizing vessels and atypical red vessels.

Tinea capitis
Comma hairs, corckscrew hairs, broken hairs, damaged hairs, black dots, zigzag hairs and interrupted hairs.


ALGORITHM

- Yellow dots: Numerous: Alopecia areata (AA)
                      A few:  Other alopecia: hypotrichosis congenita, Kerion celsie..
                                  Hair diameter diversity (≥20%), perifollicular pigmentation ⁄peripilar sign: AGA

- Black dots and/or broken hairs:  Tapering hairs (exclamation mark hairs): AA
                                                      Short vellus hairs: AA
                                                      Curled hairs: Trichotillomania                                               
                                                      No findings: AA and/or trichotillomania

                                                      Others: Tinea capitis, chemotherapy - induced alopecia, after laser depilation or trichogram.
- Others:  Perifollicular scale/sebum: Seborrheic alopecia
                Short vellus hairs, many: AA remitting
                Comma hairs: tinea capitis
                No findings: Telogen effluvium
              

UpToDate: Management of SJS/TEN.

• Early recognition and immediate withdrawal of any potentially causative agents are critical first steps in the management of SJS/TEN.
• Multiple specialists should be involved in the care of patients with SJS/TEN when possible, including experts in critical care, plastic surgery, dermatology, infectious disease, ophthalmology, and nutrition.
• For patients with extensive desquamation, we suggest transfer to a burn unit if possible (Grade 2C).
• The optimal approach to wound care has not been determined. Success has been reported with both repeated debridement of exfoliating skin, and "anti-shear" wound care, in which the necrotic skin is left in place to act as a biologic dressing.
• Sepsis is the major cause of death. Sterile handling, infection control measures, topical antibiotic agents, and surveillance cultures of possible sites of superinfection are important components of prevention. Prophylactic systemic antibiotics are not utilized by the majority of burn centers, although antimicrobials should be administered at the first sign of infection, and choice of agent should be guided by specific culture data.
• Supportive care should be the primary focus of management of SJS/TEN. Beyond this, there is insufficient evidence to establish the benefit of any adjunctive therapies (table 1). Systemic glucocorticoids and intravenous gammaglobulin (IVIG) are commonly used at many centers, although not all. Our approach is described below.
• For children (aged 16 years and younger) with SJS, we suggest NOT administering glucocorticoids (Grade 2C).
• For adult patients with mild to moderate SJS, in whom the diagnosis has been made within a few days of symptom onset, we suggest high dose, short-term systemic glucocorticoids (Grade 2C). We typically use prednisone, 2 mg per kg daily or an equivalent amount of prednisolone or methylprednisolone, initiated as soon as possible after diagnosis. Glucocorticoids are discontinued after four to seven days or at the first sign of infection.
• For pediatric and adult patients with severe SJS and TEN, we suggest IVIG (Grade 2C). We administer a dose of 1 gram/kg daily for three consecutive days. We do not administer glucocorticoids, due to concern about increasing the risk of sepsis, or employ plasmapheresis in the treatment of TEN.
• The mortality of SJS is 1 to 3 percent, while the mortality of TEN ranges from 25 to 35 percent. Predictors of mortality include older age at onset and greater extent of skin involvement. Long-term sequelae of the skin and eyes are common among survivors.

For more information:

Stevens-Johnson syndrome and toxic epidermal necrolysis: Management, prognosis, and long-term sequelae
Whitney A High, MD Milton H Nirken, MD	UpToDate

Hair Transplantation and Cicatricial Alopecia.

Unger W, Unger R & Wesley C. The surgical treatment of cicatricial alopecia. Dermatologic Therapy 2008: 21: 295–311.

Do not miss this book: Unger WP, Shapiro R. Hair Transplantation, 4th edn. New York: Marcel Dekker, 2004.


Availability of donor hair 
The long-term donor-recipient area ratio – that is, the ratio of “permanent” donor hair relative to the ultimate size of present, as well as future areas of alopecia that might develop – is perhaps the most important factor to consider. In many patients, however, the ratio is inadequate to satisfactorily treat both the current and possibly future areas of cicatricial alopecia, in addition to addressing surrounding areas that are likely to develop male pattern baldness (MPB) or female pattern hair loss (FPHL). Furthermore, if donor hair is taken from an area that is eventually destined to lose its hair secondary to MPB/FPHL or some of the diseases that cause unstable cicatricial alopecias (UCAs), it will also be lost in the recipient area.
Given the difficulty in accurately estimating this ratio, excision is generally preferable to hair transplanting. This is especially true with respect to larger alopecic regions in younger individuals, while older patients with small areas of scarring may often be appropriately treated with hair transplantation.

Scalp laxity
The less scalp laxity, the more preferable hair transplantation is to excision.

Patient’s healing characteristics 
Hypertrophic or keloid scars, less or greater than average scalp laxity (especially those with Elhers–Danlos syndrome), and individuals who have experienced inexplicable excessive postoperative bleeding in the past favor a decision to utilize hair transplantation as opposed to excision.

Vascular circulation
Grafts in the center of a large scar are most distant from a good blood supply. To test the blood supply of a large area, it is recommended that one first anesthetize a portion of the area with a 2% lidocaine solution without epinephrine. Then a 19-G needle can be used to make several incisions. There should be evidence of bleeding when this is done. If not, the area would be best treated with surgical excision.

Area of involvement
Hair transplantation is preferable in sites such as the hairline and eyebrow. If excision is employed, ideally the surgeon should use a “trichophytic” closure in which a narrow zone of the epidermis of one flap of the wound is removed and the wound is closed in such a way as to result in hair which grows through the scar itself.

Melanoma, Vemurafenib and Ipilimumab.

Vemurafenib 

It has been approved in Europe for use in the treatment of patients with unresectable or metastatic melanoma whose tumors have a BRAF mutation. About 50% of patients with melanoma have this BRAF mutation. A companion diagnostic test, the cobas 4800 BRAF V600 Mutation Test (Roche Molecular Systems), is already commercially available.A post hoc analysis showed that vemurafenib significantly improved median survival, compared with dacarbazine (13.2 vs 9.6 months): N Engl J Med 2011; 364: 2507-16.       

Potential adverse events include severe allergic reactions, severe skin reactions, cardiac events such as QT prolongation (which can be potentially life-threatening), abnormal liver function tests, eye problems, and new melanoma lesions. Common adverse effects include joint pain, rash, hair loss, tiredness, sunburn or sun sensitivity, nausea, itching, and warts.

Patients with advanced melanoma who are treated with vemurafenib should be tested for RAS mutations!! The testing is important because there is "potential for secondary tumor development" that arises from treatment with vemurafenib. Thus, patients with RAS mutations could also develop secondary cancers in organs beyond the skin, namely cutaneous squamous cell carcinoma and keratoacanthomas.

 Ipilimumab 

 

Ipilimumab is a fully human monoclonal antibody (IgG1) that blocks cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), an immune checkpoint molecule that downregulates pathways of T-cell activation. By inhibiting CTLA-4, ipilimumab acts to "release the brake" on the immune system. The role of CTLA-4 is to guard against unwanted and harmful self-directed activities (ie, autoimmunity). 

Treatment Arm	12 months (%)	18 months (%)	24 months (%)
Ipilimumab + gp100	43.6	30.0	21.6
Ipilimumab alone	45.6	33.2	23.5
gp100 alone	25.3	16.3	13.7

Hodi FS, O'Day SJ, McDermott DF et al. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 363(8), 711–723 (2010).
•• First Phase III study to demonstrate the efficacy of ipilimumab in patients with advanced melanoma. 

 

A more recent Phase III trial comparing treatment with ipilimumab with dacarbazine versus dacarbazine alone has also provided evidence for efficacy of ipilimumab in melanoma patients with improved overall survival in the ipilimumab plus dacarbazine group (11.2 months vs 9.1 months) and durable responses in a small number of patients. Robert C, Thomas L, Bondarenko I et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N. Engl. J. Med. 364(26), 2517–2526 (2011).

The current dosing of ipilimumab is 3 mg/kg of body weight, administered by intravenous infusion over 90 minutes once every 3 weeks, for a total of 4 treatments. Disease regression has been reported 3-6 months following treatment initiation. In addition, a partial response followed by stable disease has been noted. Complete responses have been recorded approximately 1 year after receiving therapy.

The most common severe immune-mediated adverse reactions are: enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy. These reactions often can be mitigated by withholding or permanently discontinuing ipilimumab, as well as by the administration of corticosteroids.  

Vismodegib for Advanced Basal Cell Carcinoma

Vismodegib is an oral drug that is designed to selectively inhibit abnormal signaling in the Hedgehog pathway, which is an underlying molecular driver of BCC. It binds to and inhibits Smoothened, a transmembrane protein involved in Hedgehog signal transduction.

Vismodegib was reviewed under the US Food and Drug Administration (FDA) priority review program offering an expedited 6-month review. It was approved for use in advanced basal cell carcinoma (BCC) ahead of the prescription user fee goal date, which was March 8, 2012.

 

Clinical Implications

• The FDA has approved vismodegib for treatment of BCC that has metastasized or relapsed after treatment with surgery, or for treatment of BCC in patients who are not candidates for surgery or radiation.

• The recommended dose of vismodegib is one 150-mg capsule orally once daily, with or without food. If a dose is missed, it should not be made up but should be resumed with the next scheduled dose.

• Vismodegib is pregnancy category D and can cause fetal harm. Men as well as women should be advised concerning pregnancy prevention and planning. Breast-feeding mothers should discontinue either vismodegib or breast-feeding, depending on how important the drug is to the mother. The safety and efficacy of vismodegib have not been established in pediatric patients or in patients with hepatic or renal impairment. 

The most common adverse reactions (incidence of 10% or more) were muscle spasms, alopecia, dysgeusia, weight loss, fatigue, nausea, diarrhea, decreased appetite, constipation, arthralgias, vomiting, and ageusia.

Therapy for Infantile Hemangiomas.

Propranolol vs Corticosteroids for Infantile Hemangiomas: A Multicenter Retrospective Analysis

Price CJ, Lattouf C, Baum B, et al. Arch Dermatol 2011;147:1371-6.

The patients were subdivided into 2 treatment groups: those receiving propranolol (n = 68; mean treatment duration, 7.9 months; target dose, 2 mg/kg/d) and those receiving oral corticosteroids (n = 42; mean treatment duration, 5.2 months; target dose, 4 mg/kg/d). To insure comparability, investigators matched these groups for patient age and lesion size, location, and type.
Outcome measures included percentage of IH clearance (< 75% or ≥ 75%), adverse effects, percentage of patients needing subsequent surgical referral, and average treatment cost per IH. Propranolol proved superior in all of these criteria:

1. 82% of patients treated with propranolol achieved ≥ 75% clearance vs 29% of patients treated with oral corticosteroids (P < .01).
2. 1 of 68 patients treated with propanolol had transient hypoglycemia, 2 patients (3%) had nonspecific skin eruptions, all patients completed treatment, and no patients suffered serious adverse events, whereas all patients treated with oral corticosteroids had adverse effects, including cushingoid features (100%), gastroesophageal reflux (n = 4), and hypertension (n = 2). One patient had a life-threatening bleed due to IH ulceration eroding into the external carotid artery.
3. 12% of patients treated with propranolol required surgery after therapy vs 29% of patients treated with oral corticosteroids.
4. The average cost per IH treated (excluding monitoring costs and prophylaxis/treatment of adverse effects) was $205.32 for propranolol vs $416.00 for oral corticosteroids

 Although "propranolol blows away corticosteroids" is the headline here, the investigators of this study also made several other important observations. For example, they found that:

1. Propranolol induced IH regression even when treatment was initiated after the first year of IH growth, confirming previous reports that the drug works to debulk more mature lesions beyond the proliferative phase.
2. Initial treatment with oral corticosteroids followed by oral propranolol showed a trend toward slightly improved efficacy over propranolol alone, although this benefit was not statistically significant.
3. IHs were less likely to relapse if propranolol therapy continued until at least 1 year of age.
4. The risk for propranolol-related side effects can be minimized with proper monitoring (eg, cardiac preclearance and checking for signs or symptoms of bradycardia, hypotension, and hypoglycemia).

Finally, Price and colleagues acknowledged that at least one more critical question remains: We still do not know how propranolol works to slow IH and induce regression. Does it trigger endothelial cell apoptosis, inhibit proangiogenic cytokines, or cause vasoconstriction by reducing nitric oxide levels? As researchers try to solve this complex puzzle, powerful new IH treatments will surely follow.

Neurofibromatosis Type 1

Major Cutaneous Features

•    Neurofibromas (60–90%)    •    Café-au-lait macules (>90%)    •    Axillary and/or inguinal freckling (∼80%)    •    Plexiform neurofibroma (25%)

 

In its fullest expression, NF1 can manifest as thousands of neurofibromas in a patient, hence the appellation neurofibromatosis (Fig. 60.3). Several variants of neurofibromas are observed in NF1. Most commonly, proliferations of spindle cells occur within the dermis, leading to cutaneous neurofibromas (CNFs). CNFs are skin-colored to pink, tan or brown, polypoid or pedunculated nodules that are soft or slightly rubbery in texture and can range from a few millimeters to several centimeters in diameter. They invaginate easily into the skin with gentle external pressure, thereby exhibiting the pathognomonic ‘buttonhole’ sign. Although these soft nodules are usually asymptomatic (except for their appearance), they may become pruritic or, occasionally, irritated. CNFs can appear as early as 4-5 years of age but more typically develop around puberty, with occasional acceleration during pregnancy.

DIAGNOSTIC CRITERIA FOR NEUROFIBROMATOSIS TYPE 1

Two or more of the following must be present:    •    Six or more café-au-lait macules >5 mm in prepubertal individuals and >15 mm in postpubertal individuals    •    Two or more neuro.bromas of any type or one plexiform neurofibroma    •    ‘Freckling’ in the axillary or inguinal regions    •    Optic gliomas    •    Two or more Lisch nodules (iris hamartomas)    •    Osseous lesion, such as sphenoid wing dysplasia or thinning of long bone cortex, with or without pseudarthrosis    •    First-degree relative (parent, sibling or offspring) with NF1 by the above criteria

 Arch Neurol. 1988;45:575–8.

A-to-T flap.

It is a double advancement flap. When primary defect remains triangular-shaped and unilateral replacement seems to be insufficient, surgeon may advence tissue bilaterally. Since their pedicle is wide, isquemia is unplausible. On forehead, due to its inelastic characteristics, it is an excellent reconstructive option for large primary defects. In addition, future scars will be hidden under facial tension lines. Frequently, displacement of Burow's triangles may be necessary.

How do you reconstruct it?

A 60-year-old patient presented this ulcerated nodule of 2.5 cm in size. Margins were papular, erythematous and well-defined. Clinical and histopathological examinations were compatible with basal cell carcinoma on her forehead. The tumor was removed succesfully, but surgical reconstruction was necessary. 

How do you do? 

Dermatologic surgery: Bilobed flap.

A patient diagnosed with basal cell carcinoma underwent surgery. Defects of the lower one-third of the nose measuring between 0.5 and 1.5 cm are the ideal size and location for the use of the bilobed flap.

Diagram from: Atlas Cirugía Dermatol. Dr. P. Redondo Bellón, 2011.

Radiación solar y cáncer cutáneo. Por: José Mª Mir Bonafé

Publicado en Mallorca Diario el 21-09-2011.

http://www.mallorcadiario.com/sanidad-y-salud/sabe-usted/radiacion-solar-y-cancer-cutaneo-84355.html

Leo con detenimiento un artículo publicado en International Journal of Dermatology en el que Narayanan y colaboradores (International Journal of Dermatology 2010: 49; 978–986) realizan una revisión del riesgo existente entre la radiación ultravioleta (RUV) y el cáncer de piel. Debido a que este tipo de publicaciones tienen como receptor un restringido sector sanitario, considero necesario transmitirles una serie de puntos considerados de salud pública. Es importantísimo conocer que:
- La RUV es el factor de riesgo más determinante para padecer cáncer cutáneo.
- Según un estudio, el 65-90% de los melanomas podrían ser atribuidos a RUV.
- La RUV provoca directamente mutaciones celulares oncogénicas e inmunosupresión.
- Las personas de piel negra presentan una incidencia de cáncer cutáneo menor a los caucásicos. Esto es debido a su mayor cantidad de melanina epidérmica, que actúa como fotoprotector.
- La depleción de la capa de ozono permite mayor filtración de RUV.
- Un descenso del nivel de ozono del 10% equivale a la escalofriante cifra de 300.000 nuevos “cáncer cutáneo no-melanoma” y 4,500 melanomas.
- Es importante conocer que estar situado a la sombra no previene totalmente de la RUV (sólo en un 50-95%).
- El fotoprotector debe ser 30 o superior y aplicado cada 2 horas.
- El mayor riesgo está comprendido entre las 10 y las 16 horas.
- Además de la exposición crónica, las quemaduras solares ocasionales representan un factor de riesgo importantísimo.
- El daño solar es acumulativo: prevenga de la exposición a los más jóvenes (nótese que parece que si visten una camiseta mojada no aporta fotoprotección).
- Resumen a los dos puntos anteriores: las quemaduras solares durante la infancia son el factor de riesgo más importante.
- A igual dosis total acumulativa al cabo de la vida, tendrá más riesgo aquél que haya recibido pocas exposiciones pero haya desarrollado quemaduras (dosis altas pocas veces), que aquél que haya estado expuesto de forma continua a dosis bajas (dosis bajas muchas veces).
- Otros factores que incrementan el riesgo son: vivir cerca del ecuador, uso de lámparas para bronceado artificial, ingesta de alcohol, tabaquismo, heridas crónicas.
- Por otro lado, el riesgo disminuye si existe alta densidad de nubes, polución o niebla.
- La RUV también produce envejecimiento cutáneo prematuro, arrugas, pérdida de elasticidad cutánea, manchas pigmentadas irregulares y alteraciones de las funciones barrera

INMUNOGLOBULINAS I.V. EN DERMATOLOGÍA: PROTOCOLO (Por: José Mª Mir Bonafé)

1. COMPOSICIÓN
- Concentración de inmunoglobulinas: ≥ 90% IgG  (también presentan cantidades variables de IgM, IgA)
- Vida media: 3-5 semanas
- Existen diferentes preparados comerciales con diferentes niveles de concentración de sodio, Osm, pH, azúcares o IgA
- Se recomiendan preparados sin sucrosa (aumenta el riesgo de insuficiencia renal), azúcares y con bajo contenido en sodio.

2. INDICACIONES EN DERMATOLOGÍA
- Fracaso de terapia convencional
- Efectos adversos de terapia convencional
- Contraindicaciones absolutas o relativas que desaconsejan la terapia de primera línea
- Curso rápidamente progresivo pese al correcto tratamiento
- Patología que presenta riesgo vital para el paciente

3. CONTRAINDICACIONES

a)    ABSOLUTAS
- Hipersensibilidad a IGIV previa
- Déficit IgA

b)    RELATIVAS
       - Embarazo
       - Necesidad vacuna viva (hasta 6 meses previa)
       - Factores de riesgo para complicaciones graves
       - Disfunción renal
       - Viscosidad sanguínea (hipergammaglob, crioglob, vasculopatía, hipercolest)
       - Antecedentes de patología tromboembólica

4. TEST PREVIOS
     
      a) RECEPTOR                                b) DONANTE
      - Hemograma                                - Serologías para VHB (HBs Ag), VHC, VIH-1, VIH-2 y Sífilis.
      - Función renal, hepática

      - Ig’s (IgA)
      - Factor Reumatoide y crioglobulinas
      - Serologías

      - Antecedentes coronarios, tromboembólicos, AVC
      - Migrañas

5. ADMINISTRACIÓN
- Tratamiento adyuvante a terapia inmunosupresora de primera elección (no se recomienda monoterapia excepto en casos especialmente indicados).
- La respuesta puede no producirse en el primer ciclo. En cambio, si no se obtiene respuesta después de 6 ciclos, se considera al paciente no respondedor y se suspenderán las IGIV.
- Se define por respuesta la no aparición de nuevas lesiones durante 10 semanas aprox. (3 ciclos aprox). En estas circunstancias se empezará a disminuir el tratamiento inmunosupresor concomitante de forma progresiva.
- Cuando se obtenga una respuesta mantenida, es posible aumentar el intervalo entre ciclos de la siguiente manera: cada 6, 8, 10, 12, 14 y 16 semanas.   
- Se finalizará el tratamiento cuando se administren 2 ciclos separados entre sí por 16 semanas sin presentar recidiva.

6. POSOLOGÍA
- Pénfigos: 1 ciclo = 400 mg/Kg/día x 5 días (total: 2gr/Kg)
- SJS/NET: 1 ciclo = 1gr/Kg/día x 3 días (total: 3gr/Kg)                        
- Un ciclo se repite cada 3-4 semanas
- Infusión lenta: 4-5 horas
- Se debe combinar con terapia tópica

7. RECOMENDACIONES DURANTE EL CICLO
- Determinación de las constantes cada 30 minutos (Importante: tensión arterial)
- Control de la función renal, hepática y hemograma diariamente
- Se recomienda el uso de un Hospital de día para evitar infecciones u otras complicaciones intrahospitalarias.
- No administrar la infusión mediante vía central (aumenta riesgo de tromboembolismos o infecciones).
- Profilaxis de efectos adversos: acetaminofeno + difenidramina previa a cada infusión

8. EFECTOS SECUNDARIOS

a) LEVES (más frecuentes, se presentan en las primeras horas de infusión)   
- Cefalea 56% (migrañas)                                       
- ↑ TA                                                   
- Febrícula, rinitis, vómitos, dolor abd, mialgias, taquicardia…               
- Vacunas vivas 6 meses post-IgIV                                   
- Maltosa: falsos+ diabetes                                       
- AVC, IAM, TVP, TEP

b) GRAVES
- NET, anafilaxia (déficit de IgA)
- Meningitis aséptica (migrañas previas)
- Hipotensión
- Insuficiencia renal aguda  
- Edema agudo de pulmón
- Citopenias

  
9. DERMATOSIS SECUNDARIAS                                   
- Urticaria
- Eccema
- Liquenoide
- Petequias
- Prurito en palmas
- Alopecia
- Vasculitis leucocitoclástica


Fuente: José Mª Mir-Bonafé (H. C. U. Salamanca)

Bibliografía recomendada:

Guidelines on the use of high-dose intravenous immunoglobulin in dermatology. Eur J Dermatol 2009 ; 19 (1) : 90-98.

What’s new in i.v. immunoglobulin therapy and pemphigus: High-dose i.v. immunoglobulin therapy
and its mode of action for treatment of pemphigus. Journal of Dermatology 2010; 37: 239–245

Differential diagnosis in bullous diseases

There are certain situations in which diagnosis of bullous disease is not that easy. Here it is presented a table explaining the most important features of 3 of them. Please, note that this content is relevant since all 3 may present identical histopathology!

From: Bolognia: Dermatology, 2nd ed.