Hair loss is a common problem that can have a significant impact on an individual’s quality of life. Telogen effluvium (TE) and anagen effluvium (AE) are two types of hair loss that can occur due to various factors. It is important to note that neither TE nor AE are scarring types of hair loss. In both conditions, the hair loss is typically temporary and the hair follicles are not permanently damaged. However, in rare cases, if the underlying cause is not identified and addressed, the hair loss may become permanent. In this article, we will discuss the etiology, pathophysiology, clinical features, presentation, diagnosis, management, prognosis, and complications of TE and AE.

Etiology

The etiology of TE and AE differs. TE can be triggered by a range of physical and emotional stressors, such as pregnancy, surgery, illness, or medications. In contrast, AE is usually caused by exposure to certain toxins, medications, or radiation therapy.

Pathophysiology

The pathophysiology of TE and AE is distinct. In TE, the hair follicles are prematurely pushed into the resting phase of the hair growth cycle (telogen phase), resulting in an increase in the number of hairs shed from the scalp. AE involves damage to hair follicles during the growing phase of the hair growth cycle (anagen phase), leading to sudden and widespread hair loss.

Clinical Features

The clinical features of TE and AE vary depending on the underlying cause. In TE, the hair loss is gradual and diffuse, and there is usually no noticeable thinning of the hairline. In contrast, AE is characterized by sudden hair loss, which may be accompanied by redness or itching of the scalp.

Presentation

The presentation of TE and AE also differs. In TE, hair loss is typically gradual and may occur over several months. Patients may notice an increase in shedding when brushing or washing their hair. In contrast, AE is characterized by sudden hair loss, which may occur within a few days or weeks. Patients may notice clumps of hair falling out when they brush or wash their hair.

Diagnosis

The diagnosis of TE and AE is usually made based on the patient’s history and physical examination. Blood tests may be ordered to rule out underlying medical conditions that could be causing the hair loss. A scalp biopsy although is rarely needed, it may also be performed to confirm the diagnosis.

Management

The management of TE and AE depends on the underlying cause. In many cases, the hair loss will resolve on its own once the underlying cause is identified and addressed. However, if the hair loss is causing significant distress, there are treatments available to help promote hair regrowth. These may include topical medications, oral medications, or hair transplant surgery.

Prognosis

The prognosis for TE and AE is generally good, as the hair loss is usually temporary and will resolve once the underlying cause is addressed. However, in some cases, the hair loss may be permanent.

Complications

Complications of TE and AE are rare but can occur if the underlying cause is not identified and addressed. In some cases, the hair loss may be permanent, leading to significant distress and decreased quality of life. Additionally, if the hair loss is caused by an underlying medical condition, there may be other health complications that need to be addressed. 

 

Written by

Deemah AlHuraish, medical student

Revised by

Maee Barakeh, medical student

References

UpToDate

DermNet

Background

Alopecia areata is an autoimmune condition that causes the body to attack the hair follicles, resulting in hair loss. Typically, this condition is characterized by round patches of non-scarring hair loss; and occasionally, nails changes.
It is estimated that the lifetime risk of alopecia areata is approximately 2%. According to the data, 25 to 36 years of age seems to be the average age of onset.

Etiology

It has been hypothesized that the loss of immunity associated with anagen hair follicles plays a key role in the pathogenesis of this disease. Also, genetic factors are involved in disease susceptibility and severity.

Comorbidities

Alopecia areata was found to be associated with several comorbidities, including depression, anxiety, and other autoimmune diseases, such as thyroid disease, lupus erythematosus, vitiligo, psoriasis, rheumatoid arthritis, and inflammatory bowel disease.

Clinical features 

Alopecia areata may present in different patterns. Patchy alopecia areata is the most common pattern; it is characterized by well-circumscribed round/oval patches of hair loss with normal skin appearing. Other less common patterns include, alopecia totalis which presents as complete loss of scalp hair, and alopecia universalis which presents as complete loss of body hair.
The scalp is most commonly affected by this condition, but any other area that bears hair can also be affected. The involvement of nails is generally indicative of a more severe type of hair loss. Usually, this condition manifests itself within a short period of time and may progress to the point of hair loss.

Diagnosis

Typically, alopecia areata is diagnosed based on the clinical features of the condition. Additionally, there are several helpful tools that can help support the diagnosis, including dermatoscopes, hair pull tests, and skin biopsy. Dermoscopic findings of active disease include exclamation point hairs, broken hairs, yellow dots, and black dots.

Management

Alopecia areata has an unpredictable course and may improve on its own. There is a wide range of treatments that is available for the management of alopecia with varying degrees of success. Generally intralesional and topical corticosteroids are considered first-line treatment for most patients.
For mild cases, options include Intralesional corticosteroid injections, topical treatments with corticosteroids or minoxidil. For more advanced cases, topical immunotherapy is used.  Systemic therapies are reserved for severe or refractory diseases, including systemic glucocorticoids and immunosuppressants such as cyclosporine and methotrexate. The FDA has recently approved Baricitinib, which is a JAK inhibitor with promising outcomes for alopecia treatment.

Written by

Ghida Altammami, medical student

Revised by

Maee Barakeh, medical student

References

DermNet

National Library of Medicine

Bolognia textbook of dermatology

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