What is piebaldism

Piebaldism is an uncommon inherited pigmentation disorder manifesting at birth with patchy leukoderma (white skin) and white hair (poliosis). Consequently, the most prominent trait of piebaldism is a white forelock (a patch of white hair immediately above the hairline). Piebaldism is an autosomal dominant genetic condition, so each offspring of an affected parent has a 50% chance of inheriting the disorder.

Epidemiology of piebaldism

The incidence of piebaldism is unknown but is estimated to range between 1:40,000 and 1:100,000. Both genders are affected equally. There is no difference in prevalence between ethnic groups, but the disorder is more noticeable and readily identifiable in people with darker skin tones.

Causes of piebaldism

75% of cases of piebaldism are due to mutations of the KIT proto-oncogene on chromosome 4; over 45 distinct point mutations, deletions, nucleotide splice mutations, and insertions of the KIT gene have been identified. The KIT gene mutation causes abnormal migration of melanoblasts from the embryonic neural crest to the epidermis, resulting in melanocyte-deficient skin patches.

Clinical features of piebaldism

White forelock, leukoderma of the central portion of the forehead, eyebrow and eyelash hair may also be affected, white patches of face, trunk, and extremities, and a narrow border of hyperpigmented skin surround the white unpigmented patches are the clinical characteristics of piebaldism. In the mild form, only small patches of leukoderma may be present, whereas in the severe form, the forelock is white and there are larger white patches on the trunk and extremities.

Diagnosis of piebaldism

Piebaldism is clinically diagnosed at birth or shortly thereafter. A leukoderma skin biopsy specimen will reveal the absence of melanocytes and melanin pigment. The diagnosis can be confirmed by genetic testing of a peripheral blood sample.

Management of piebaldism

The treatment begins with sun protection measures, solar avoidance during peak UV exposure hours, and self-examination of the skin to detect skin cancer. The surgical and procedural treatment consists of dermabrasion followed by melanocyte-enriched cell suspensions, melanocyte transplant, suction epidermal grafting, or full-thickness punch grafting. There may be a need for a combination of these methods, which can be enhanced by UV light therapy. Cosmetic camouflage techniques can conceal hair and skin pigmentation changes.

Complications of piebaldism

The complications of piebaldism include sunburn, skin cancers, and psychosocial consequences.

Written by

Mohammed Alahmadi, Medical Student.

References

DermNet

UpToDate

Epidemiology of NLD

Necrobiosis lipoidica diabeticorum (NLD) is a rare granulomatous skin disorder that has a female predominance, with an approximate ratio of  3:1. It has been linked to diabetes mellitus; as up to 65% of NLD patients have diabetes or prediabetes; however, only 0.03% of patients with diabetes have NLD. The control of blood glucose levels usually does not have a significant effect on the course of NLD. In spite of that, diabetic patients with NLD do appear to have a higher rate of diabetes-related complications compared to diabetic patients without NLD. 

Pathogenesis of NLD

The cause of NLD remains unknown. It is postulated that immunologically mediated vascular disease is the primary cause of the altered collagen seen in NLD. Other theories suggest that microangiopathic vessel changes seen in diabetic patients could contribute to the development of collagen degeneration and subsequent dermal inflammation.

Clinical features of NLD

NLD starts as red–brown papules that are typically multiple and symmetrical on both shins. Later, it progresses into yellow–brown, atrophic, telangiectatic plaques surrounded by raised, violaceous rims. Pretibial region is the typical anatomical site for NLD, and it is less commonly seen in other sites including upper extremities, face and scalp. NLD is typically asymptomatic; however, some patients report pruritus, dysesthesia or pain. 

Diagnosis of NLD

NLD is diagnosed clinically when typical. A biopsy specimen from the palpable inflammatory borders is used to confirm the diagnosis. The histopathology is characteristic; it shows granulomatous epithelioid histiocytes arranged in a palisaded fashion around destroyed collagen (necrobiosis). The inflammation extends throughout the dermis and into subcutaneous fat septae.

Management of NLD

No treatment for NLD has proven to be effective. However, intralesional corticosteroids injected into the active borders of established lesions can be used as first-line treatment to halt disease progression and extension into the surrounding normal skin. In extensive ulcerations that are refractory to medical treatment, surgical management and skin grafting can be considered. 

Complications of NLD

Ulceration is a common complication for NLD that is seen in 1/3 of the cases, usually preceded by a minor injury to an established patch. Secondary bacterial infection, delayed healing and squamous cell carcinoma have been reported to develop in ulcerated NLD.

Written by

Maee Barakeh, medical student

References

Bolognia textbook of dermatology

DermNet

Porphyrins pathway is involved in heme synthesis, which is the red pigment that gives red blood cells their distinctive color. Disturbance in one of the enzymes of the pathway will lead to accumulation of the intermediate molecules.
Porphyria cutaneous tarda (PCT) is the most common human porphyria caused by hepatic deficiency of uroporphyrinogen decarboxylase (UROD). Clinical picture is limited to cutaneous manifestations.
In 1⁄3 of patients, familial autosomal dominant UROD mutation is the underlying cause of the disease. However an underlying acquired cause could be the culprit as well.
Acquired causes:
● Presence of iron overload ● Alcohol abuse
● Infections (HIV and HCV) ● Smoking
PCT can occur at any age but the peak incidence is around 5th or 6th decade. It also occurs in both genders but a slight predilection for men.
It can present as increased photosensitivity due to the porphyrin associated with skin fragility and blistering in sun-exposed areas, i.e the hands and the forearms. Most notably the color of the urine becomes darker, with a reddish hue.

Treatment of the underlying problems yields the good results. Phlebotomy is the main treatment for PCT, it can effectively treat the problem. If the patient is geriatric or anemic, the use of hydroxychloroquine is advisable to excrete porphyrins more easily.

Written by: Naif Alalshaikh, medical student

References:

“Porphyria Cutanea Tarda.” DermNet, https://dermnetnz.org/topics/porphyria-cutanea-tarda.

Singal, Ashwani K. “Porphyria Cutanea Tarda: Recent Update.” Molecular Genetics and Metabolism, vol. 128, no. 3, 2019, pp. 271–281., https://doi.org/10.1016/j.ymgme.2019.01.004.

Psoriasis is being treated with a variety of medicines that are currently being researched. These treatments are intended to treat psoriasis through a number of methods, including:

Therapies targeting the Th17 pathway – Interleukins (ILs) from the T helper type 17 (Th17) pathway (IL-23 and IL-17) play a key role in psoriasis pathogenesis and have become therapeutic targets:

Bimekizumab – Bimekizumab, a monoclonal IgG1 antibody that suppresses IL-17A and IL-17F, has been shown to be effective in phase III randomized studies. Adults with moderate to severe plaque psoriasis were randomly randomized to receive bimekizumab (320 mg every four weeks) or placebo in a 4:1 ratio in the BE READY study (n = 435). At week 16, 317 of 349 bimekizumab patients (91%) had a 90 percent improvement in the Psoriasis Area and Severity Index (PASI 90), compared to only 1 of 86 patients (1%) in the placebo group. Over the next 40 weeks, patients in the bimekizumab group who attained PASI 90 were randomly assigned (1:1:1) to receive bimekizumab 320 mg every four weeks, bimekizumab 320 mg every eight weeks, or placebo. Patients who received bimekizumab every four or eight weeks were more likely than those in the placebo group to reach PASI 90 at week 56. (87, 91, and 16 percent, respectively). Nasopharyngitis, oral candidiasis, and upper respiratory tract infections were the most prevalent treatment-emergent adverse events for bimekizumab.

Bimekizumab, ustekinumab, and placebo were tested in the BE VIVID study (n = 567) for effectiveness and safety. For 16 weeks, adults with moderate to severe plaque psoriasis were given bimekizumab (320 mg every four weeks), ustekinumab (weight-based dosage of 45 or 90 mg at weeks 0 and 4, then every 12 weeks), or placebo (every four weeks). Patients in the placebo group switched to bimekizumab at week 16, while those in the active treatment groups stayed on it until week 52. Patients in the bimekizumab (n = 321) group were more likely than those in the ustekinumab (n = 163) and placebo (n = 83) groups to attain PASI 90 at week 16. (PASI 90 achieved in 85, 50, and 5 percent of patients, respectively). Nasopharyngitis, oral candidiasis, and upper respiratory tract infection were the most prevalent treatment-emergent adverse events for bimekizumab, with candidiasis occurring more often in the bimekizumab group than in the ustekinumab group. Over the course of 52 weeks, five serious cardiac adverse events occurred in bimekizumab-treated individuals with pre-existing cardiovascular risk factors, but none happened in the ustekinumab-treated group.Oral candidiasis was more common than with other IL-17 pathway inhibitors, and one instance of inflammatory bowel illness was reported. Additional research might help to clarify the issue of safety.

Trials comparing bimekizumab to adalimumab or secukinumab show that bimekizumab is more effective. Adults with moderate to severe plaque psoriasis were randomly allocated to bimekizumab (320 mg every four weeks for 56 weeks), bimekizumab (320 mg every four weeks for 16 weeks and then every eight weeks until week 56), or adalimumab in a 56-week phase III study (BE SURE trial) (80 mg followed by 40 mg one week later and then 40 mg every two weeks until week 24).

Patients who received adalimumab were then given bimekizumab (320 mg every four weeks from week 24 to 56). At week 16, 275 of 319 patients (86%) who received bimekizumab had a PASI of 90, compared to 75 of 159 patients (47%) who received adalimumab (adjusted risk difference 28.2 percentage points, 95 percent CI 19.7-36.7). With both bimekizumab dose regimens, responses were sustained until week 56.

Adults with moderate to severe plaque psoriasis were randomly allocated to bimekizumab (320 mg every four weeks) or secukinumab in a 48-week phase III study (BE RADIANT trial) (300 mg weekly to week 4 and then once every four weeks). Bimekizumab patients were rerandomized at week 16 to receive bimekizumab once every four weeks or once every eight weeks. At week 16, 230 of 373 bimekizumab patients (62%) had complete eradication of skin disease on the Psoriasis Area and Severity Index (PASI 100), compared to 181 of 370 patients (49%) in the secukinumab group (adjusted risk difference 12.7 percentage points, 95 percent CI 5.8-19.6). Bimekizumab’s effectiveness remained better after 48 weeks (PASI 100 in 67 versus 46 percent of patients). The study’s power to identify differences between the two bimekizumab maintenance therapy groups was insufficient.

Tapinarof – Tapinarof is a topical aryl hydrocarbon receptor-modifying drug that may help with psoriasis by modulating Th17 cytokines including IL-17A and IL-17F, as well as normalizing the skin barrier and providing antioxidant action. A total of 1025 persons with chronic plaque psoriasis encompassing 3 to 20% of total body surface area were randomly allocated in a 2:1 ratio to either tapinarof 1 percent cream or vehicle used once daily in two similar phase III studies (PSOARING 1 and PSOARING 2). Patients in the tapinarof groups were more likely than patients in the placebo group to achieve the primary endpoint of a PGA score of 0 (clear) or 1 (almost clear) and a two-point decrease in the five-point PGA scale at week 12. (35.4 versus 6 percent [adjusted difference 29.4 percentage points; relative rate 5.8, 95 percent CI 2.9-11.5] in PSOARING 1 and 40.2 versus 6.3 percent [adjusted difference 33.9 percentage points; relative rate 6.1, 95 percent CI 3.3-11.4] in PSOARING 2). The tapinarof groups improved 75% more than the vehicle groups in terms of the Psoriasis Area and Severity Index (PASI 75) and PASI 90 rates. In the tapinarof groups, foliculitis, contact dermatitis, and headache were more common than in the other groups. In the tapinarof groups, folliculitis, contact dermatitis, and headache were more common than in the vehicle groups.

Small molecules – Other possible treatments include a variety of tiny compounds that aim to disrupt cellular signaling, which is crucial for the propagation of the inflammatory response. Small compounds that block Janus kinases (JAKs), lipids, a protein kinase C inhibitor, a selective tyrosine kinase 2 (TYK2) inhibitor, and crisaborole, a topical phosphodiesterase 4 inhibitor are some of the small molecules being researched for the treatment of psoriasis:

• In randomized studies, oral tofacitinib, a small molecule JAK inhibitor licensed for the treatment of psoriatic arthritis, was beneficial for moderate to severe plaque psoriasis. Tofacitinib 10 mg twice daily was superior to placebo and noninferior to etanercept in a phase III trial that randomly assigned 1106 adults with moderate to severe plaque psoriasis to treatment with tofacitinib 10 mg twice daily, tofacitinib 5 mg twice daily, etanercept (50 mg twice weekly), or placebo.By week 12, 64, 40, 59, and 6% of patients receiving tofacitinib 10 mg twice daily, tofacitinib 5 mg twice daily, etanercept, and placebo, respectively, had met this objective. Other phase III studies found tofacitinib 10 mg twice daily and tofacitinib 5 mg twice daily to be helpful for chronic plaque psoriasis. The finest outcomes come from taking 10 mg twice a day. Tofacitinib has a quick beginning of action, with responses visible by week 4, and there is evidence of tofacitinib’s effectiveness for up to two years. In most cases, the treatment is well tolerated. Tofacitinib may make you more susceptible to infection. Cholesterol and creatine phosphokinase levels may also rise during treatment. A phase II randomized study also indicated that a topical formulation of tofacitinib was more efficacious than vehicle for plaque psoriasis.
• In a phase II, dose-ranging, randomized study, baricitinib, another oral reversible inhibitor of JAK1/JAK2 tyrosine kinases, was examined for the treatment of moderate to severe psoriasis. 271 participants were randomly randomized to receive daily dosages of baricitinib 2, 4, 8, or 10 mg, or a placebo, in this trial. More patients in the baricitinib 8 and 10 mg groups attained PASI 75 at 12 weeks than those in the placebo group (43, 54, and 17 percent, respectively). Infections, lymphopenia, neutropenia, anemia, and an increase in creatine phosphokinase were more prevalent among patients receiving the highest baricitinib dosages.
• Selective inhibition of TYK2, an intracellular signaling enzyme implicated in psoriasis pathogenesis, using the experimental drug BMS-986165 was related with clinical improvement in people with moderate to severe psoriasis in a phase II study (n = 268) [237]. Participants were allocated to one of five BMS-986165 dosage regimens or a placebo. More patients receiving 3 mg daily, 3 mg twice daily, 6 mg twice daily, or 12 mg daily of BMS-986165 attained PASI 75 after 12 weeks than patients receiving placebo (39, 69, 67, 75, and 7 percent, respectively). A three-milligram dosage given every other day did not outperform the placebo. In the active therapy groups, adverse events were more prevalent. Nasopharyngitis, headache, diarrhea, nausea, and upper respiratory infection were the most prevalent side effects. Mild to severe acne was more common in the active treatment groups, and one melanoma diagnosis was made in the 3 mg daily group.
• Sphingosine 1-phosphate receptor 1 (S1PR1), a receptor involved in lymphocyte migration from secondary lymphoid tissues into the bloodstream, might be another viable treatment for psoriasis. Ponesimod, a selective S1PR1 modulator also being explored for the treatment of multiple sclerosis, causes S1PR1 internalization, preventing lymphocyte egress triggered by sphingosine 1-phosphate (S1P). Individuals treated with ponesimod were considerably more likely than patients treated with placebo to attain PASI 75 after 16 weeks in a phase II randomized study including 326 patients with moderate to severe chronic plaque psoriasis.
• Treatment with a glucagon-like peptide 1 (GLP-1) analog (exenatide or liraglutide) seems to induce moderate improvement in psoriasis in people with both psoriasis and type 2 diabetes in small, uncontrolled studies. Liraglutide, on the other hand, was shown to be ineffective for plaque psoriasis in a placebo-controlled randomized study (n = 20).
• Treatment with topical crisaborole, a phosphodiesterase 4 inhibitor, has been linked to improvements in facial psoriasis, intertriginous psoriasis, and palmoplantar psoriasis, all of which manifest as erythematous plaques, papules, and deep-seated pustules on the palms and soles, according to case reports.

Topical calcineurin inhibitor – Treatment with topical crisaborole, a phosphodiesterase 4 inhibitor, has been linked to improvements in facial psoriasis, intertriginous psoriasis, and palmoplantar psoriasis, all of which manifest as erythematous plaques, papules, and deep-seated pustules on the palms and soles, according to case reports.

written by: Lama Altamimi, medical intern

references:

UPTODATE

Mycosis Fungoides (MF) is a form of non-Hodgkin lymphoma that is considered the most common type of primary cutaneous T-cell lymphoma (CTCL).MF is a neoplasia of malignant monoclonal T lymphocytes that generally invades the skin and causes cutaneous signs and symptoms.It is characterized clinically during early stages as erythematous scaly patches and plaques, or during advanced stages as tumors or erythroderma, with lymph node and/or visceral involvement.And histologically presents as an epidermotropic infiltrate of small-medium sized CD4+ T lymphocytes with cerebriform nuclei. Mycosis Fungoides (MF) is the most prevalent cutaneous T-cell lymphoma, accounting for 50-65% of cases. Typically seen in men [1.6-2:1] ratio and appears in late adulthood with 55-60 years as a median age of diagnosis. Even so, MF is a rare and uncommon condition, the incidence of MF in the United States is approximately 0.3-1.02 new cases per 100.000/year. MF follows an indolent clinical course over years, with an estimated 5-year survival rate of 87% and a median survival of 11.4 years. Also patients who present with involvement of lymph nodes or viscera have a median survival of <1.5%.
MF natural history is a classical slow progression from patches to plaques to tumors stage typically on unexposed areas such as the trunk, buttocks and thighs. Due to MF manifesting a variety of clinical and pathological presentations, atypical presentations of MF may be difficult to diagnose. Within this broad spectrum of clinical presentations, the World Health Organization (WHO) classified MF into 3 main variants or subtypes; folliculotropic MF, pagetoid reticulosis, and granulomatous slack skin.

Patch stage:
● Poorly defined, irregular, finely scaling, red patches of variable size often with atrophic (thin, wrinkled) skin
● Occurs mainly on sun-protected sites particularly the lower trunk, thighs and, in women, the breasts
● Often asymptomatic
● Hypopigmented variant: pale, finely scaly patches without atrophy in children and Fitzpatrick skin types
IV-VI
● Poikiloderma atrophicans vasculare is atrophic patch stage MF presenting with skin thinning, pigment
changes, and dilation of capillaries (telangiectasia)
Plaque stage:
● Well-demarcated annular or arciform itchy thickened lesions
● Color often red, violaceous, or brown, sometimes scaly
Tumor stage:
● Large irregular lumps (>1 cm) developing from plaques
● Deep red to violaceous color, often shiny surface

Diagnosis:
The diagnosis of mycosis fungoides requires careful clinicopathological correlation. Dermoscopy can help to distinguish MF from inflammatory dermatosis.

Treatment:
Mycosis fungoides is treatable, not curable. There are no globally accepted treatment guidelines. Treatment should be guided by the patient’s wishes, stage of disease, availability of options, and local expertise.

Topical treatment:
● Topical steroids
● Topical chemotherapy eg, nitrogen mustard, carmustine
● Topical bexarotene
Procedural treatment:
● Phototherapy — PUVA, narrowband UVB
● Radiotherapy and whole-body total skin electron beam therapy
● Extracorporeal photopheresis
Systemic treatment:
● Chemotherapy — mycosis fungoides is relatively chemoresistant
● Immunotherapy — interferon-alpha
● Oral retinoids and rexinoids (eg, bexarotene)
Only brentuximab vedotin (for CD30+ MF) and allogeneic haematopoietic stem cell transplant alter the natural history of the disease.

Written by: Khalid Nagshabandi, medical student

Reference: DermNet

Sézary syndrome (SS) is a leukemic type of cutaneous T cell lymphoma (CTCL) in which the peripheral blood contains a large number of circulating malignant (Sézary) cells. SS is assumed to be made up of mature epidermotropic skin homing CD4+ T cells or central memory T cells. The goal of this discussion is to go over the clinical characteristics of SS.

Skin lesions — SS patients typically have extensive erythema that is finely scaled, indurated, or resembles livedo reticularis. The severity of erythema and the amount of body surface area (BSA) involved may fluctuate, but at some point during the disease’s course, the skin involvement must cover >80% of the BSA to meet the SS definition from The International Society for Cutaneous Lymphoma (ISCL), European Organization for Research and Treatment of Cancer (EORTC), and United States Cutaneous Lymphoma Consortium (USCLC).

The following is an overview of the skin lesions:

• Keratosis pilaris-like lesions –Follicular involvement may be characterized by inflamed follicular-based papules or scale.
• Alopecia – Alopecia is common and manifests as a loss of hair density all over the scalp and body, or as patches of alopecia.
• Ectropion – Because of the tautness and induration in the skin, an outward tilting of the lower eyelid with increased exposure of the ocular surface and sensitive mucous membranes of the inner lid might develop, which may be related with disruption of normal tear drainage pattern.
• Keratoderma – Keratoderma, or thicker keratin retention on the palms and soles, is a typical feature that can help distinguish SS from other causes of erythroderma, but it can also make the diagnosis between SS and pityriasis rubra pilaris difficult.
• Hypertrophic nails – Because of the involvement of the posterior nail fold, the nails may become hypertrophic.
• Erosions and superinfection –Patients are frequently colonized with Staphylococcus aureus, and persistent scratching causes erosions and superinfection.
• Focal areas of scaling – Tinea corporis is prevalent, and if scaly areas are present, a potassium hydroxide preparation should be conducted.
• Lichenification – Long-term disease, chronic pruritus, and scratching can cause diffuse lichenification, which is defined as thickening skin with enlarged skin lines. Fissures are a regular occurrence.

Lymphadenopathy — Peripheral lymphadenopathy is common, and a biopsy usually reveals either dermatopathic changes or lymphoma-like alterations, both of which are linked to the underlying cutaneous lymphoma.

Viscera — The prevalence of visceral involvement in SS patients is unknown. Because bone marrow examination is not frequently conducted, unless in the case of unexplained hematologic abnormalities, the prevalence of bone marrow involvement is unknown.

Pruritus — The most common and debilitating symptom of SS sufferers is pruritus. The length and depth of erythema, as well as the degree of blood involvement, are not always connected to the degree of pruritus. Pruritus can make sleep problems, anxiety, and depression worse.

Written by: Lama Altamimi, medical intern.

Reference: UptToDate

https://www.uptodate.com/contents/clinical-presentation-pathologic-features-and-diagnosis-of-sezary-syndrome?search=%20S%C3%A9zary%20syndrome&source=search_result&selectedTitle=1~58&usage_type=default&display_rank=1#H449464055