Clinicopathological characteristics of cutaneous complications following COVID-19 vaccination: A case series.

INTRODUCTION: Several vaccine-related cutaneous adverse events occurred following the widespread use of vaccines to prevent coronavirus disease 2019 (COVID-19). This case series reports 25 patients with de novo or accentuated dermatologic conditions after receiving the Sinopharm, Sputnik V, AstraZeneca, or BIV1-CovIran vaccine in Iran. METHODS AND RESULTS: Twenty-five eligible patients with a mean age of 46.80 years were investigated. The cutaneous adverse events included pityriasis rosea, zoster, viral exanthema, urticaria, bullous pemphigoid, pemphigus vulgaris, and acute generalized exanthematous pustulosis. The manifestations appeared 14.45 ± 6.98 and 20.79 ± 22.18 days following injection of the first and second doses of COVID-19 vaccines, respectively. All patients experienced new cases of cutaneous disease other than two who developed flare-ups of lichen planus and psoriasis. CONCLUSION: Several cutaneous reactions, ranging from allergic events to skin diseases, have been reported following the injection of COVID-19 vaccines. Focal injection-site reactions are the most common cutaneous adverse events; however, de-novo skin diseases and a flare-up of preexisting cutaneous disorders have also been described. Although many cases of COVID-19 vaccine-related cutaneous diseases have been published, our zoster/lichen planus and AGEP cases after vaccination are interesting. A more detailed understanding of cutaneous adverse events following COVID-19 vaccination will facilitate better diagnosis and management.

Iranian psoriasis registry: Research protocol and preliminary results of a pilot study.

BACKGROUND: Psoriasis as a common cutaneous inflammatory disease affect many aspects of patients' life. Disease registries render it possible to collect valuable data regarding a disease prevalence and burden as well as long-term observations concerning possible therapeutic regimens. METHODS: This registry was designed for the ongoing systematic data collection on patients with psoriasis at two referral dermatology centers in Iran. The pilot phase of the registry was used to identify possible obstacles in the application and execution of systematic registration. RESULTS: A total of 281 patients were registered with the mean age of 42.02 years. The disease duration was 12.06 ± 10.90 years with the variety of clinical presentations. There was no significant difference between males and females in the age of disease onset (p = 0.53). Notably, 167 patients had children. Among them, 13 had children with psoriasis. The gender of the affected parent did not affect the possibility of psoriasis transmission to the child, and no significant difference was seen between the two sexes (P = 0.569). Regarding treatment, 99.4% of patients (n = 280) had used topical agents, 52.3% (n = 147) biologics, and 60.9% (n = 171) nonbiologic medications. CONCLUSION: Clinical trials report the efficacy and safety data regarding limited study populations in a restricted time window, and the results may differ from the general population. This highlights the importance of registry-based studies for collecting and analyzing longitudinal information. In terms of long-term disease complications such as malignancies, cardiovascular events, and serious adverse events, registry-based studies will help clinicians better recognize and manage each disease.

Facial pyoderma gangrenosum associated with fallopian tube carcinosarcoma.

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis associated with underlying disorders. The association between PG and solid organ tumors (SM), including gynecologic cancers, has been previously reported. Here, we report a case of a 61-year-old woman with pyoderma gangrenosum on the posterior auricular region associated with an underlying fallopian tube carcinosarcoma: a rare and aggressive gynecologic malignancy. The patient's ulcer responded favorably to treatment, and surgical resection of the tumor was performed. The patient was then referred for further cancer management. No new lesions or recurrences were found over the 18 months of routine follow-up.

Recalcitrant course of bullous pemphigoid indicating coexisting hypereosinophilic syndrome: A case report and literature review.

Key Clinical Message: As dermatologists, we must be aware that even limited localized lesions may signal a life-threatening condition, for which early diagnosis and treatment can improve the prognosis. Abstract: Bullous pemphigoid is an autoimmune disorder characterized by blister formation. Hypereosinophilic syndrome is a myeloproliferative disorder featuring papules, nodules, urticarial lesions, and blisters. The coexistence of these disorders may highlight the involvement of common molecular and cellular factors. Here, we describe a 16-year-old patient with hypereosinophilic syndrome and bullous pemphigoid.

The frequency of fatty liver in patients with alopecia areata: A case-control study.

BACKGROUND: Alopecia areata (AA) is an immune-mediated nonscarring hair loss disorder with multiple subtypes, including alopecia universalis (AU). Previous studies have shown a link between serum lipid profile and alopecia. We aimed to investigate the frequency of fatty liver in patients with AU and patchy alopecia areata (PAA) compared to a control group. METHODS: This case-control study included patients with AU and PAA referred to a dermatology clinic from September 23, 2019 to September 23, 2020. A group of individuals without hair loss disorders attending the same clinic were selected as controls. Participants' general information, including age, sex, weight, height, and waist circumference (WC), was recorded. Body mass index (BMI) was calculated for all participants. Also, hyperlipidemia and statin use were noted and liver enzymes were evaluated. For AU and PAA patients, disease duration and the Severity of Alopecia Tool (SALT) score were also recorded. Then, all subjects underwent ultrasound to assess fatty liver and its grade. RESULTS: Overall, 32 patients were included in each group. All three groups were comparable in age, sex, weight, height, BMI, WC, hyperlipidemia, abnormal liver enzymes, and statin use. Disease duration and SALT score were significantly higher in the AU than in the PAA group (p = 0.009 and p < 0.001, respectively). The frequency of fatty liver was the highest in AU patients (40.6%), followed by 34.4% in PAA patients, and 21.9% in controls (p = 0.263). This was also the case for grade-1 fatty liver, while grade-2 was more common in PAA patients, and grade-3 was only observed in one patient from the AU group (p = 0.496). CONCLUSIONS: Fatty liver was more frequent in AU and PAA patients than controls, without statistically significant differences. There might be an association between fatty liver and AA, particularly the AU subtype.

Split-face comparison of hydroquinone 4% plus nitrogen plasma vs. hydroquinone 4% alone in the treatment of melasma.

Treatment of skin diseases is important yet challenging. One of the most common skin diseases in women is melasma, which features acquired facial hyperpigmentation. We studied the effect of cold atmospheric nitrogen plasma on this disease. To characterize the nitrogen plasma, we obtained the relative intensity of the species and the plasma temperature and skin temperature during processing at different input powers and gas flows. Patients complaining of melasma were treated with hydroquinone on both sides of the face, and one side was randomly selected for additional nitrogen plasma therapy. Eight treatment sessions of plasma processing were provided 1 week apart, and one follow-up session was scheduled 1 month after the end of treatment. The rate of improvement was scored by a dermatologist in the eighth session and 1 month following the last session using the modified Melasma Area Severity Index (mMASI). Skin biomechanical characteristics such as melanin, cutaneous resonance running time (CRRT), transepidermal water loss (TEWL), and hydration were measured at baseline and during the fourth, eighth, and follow-up sessions. On both sides, we observed a significant decrease in both CRRT and melanin (P < 0.05). TEWL did not change on both sides, while hydration decreased significantly only on the side to which hydroquinone was applied in isolation (P < 0.05). According to clinical scores, on both sides, we had significant improvement. On the side that plasma was not applied, the percentage reduction of pigmentation (mMASI) in the eighth and follow-up sessions in comparison with the baseline was 5.49 ± 8.50% and 33.04 ± 9.17%, respectively, while on the other side, these figures were 20.57 ± 6.64% and 48.11 ± 11%. For melanin, these figures were 13.84 ± 4.84% and 18.23 ± 7.10% on the hydroquinone side and 21.56 ± 3.13% and 23.93 ± 3.02% on the other side. According to these results, nitrogen plasma can safely complement topical hydroquinone to improve clinical outcomes when treating melasma without causing stratum corneum damage or skin discomfort, though confirmatory studies are needed.

Brain MRI findings in patients with bullous pemphigoid: A case-control study.

Evidence suggests that bullous pemphigoid (BP) is associated with multiple neurological disorders. We aimed to compare brain magnetic resonance (MRI) findings between BP patients and a control group. This case-control study included patients with BP referred to two dermatology clinics during a two-year period. A group of individuals attending the same clinics for cosmetic procedures were selected as controls. First, participants' general information including age, gender, education, weight and underlying disease was recorded. For BP patients, the drugs and the BP Disease Area Index (BPDAI) were recorded as well. Then, all participants underwent brain MRI without contrast. The Fazekas scale, the general cerebral atrophy (GCA) score, and the Medial Temporal lobe Atrophy (MTA) score were used to assess MRI images. Overall, 24 BP patients and 24 controls were evaluated in this study. Both groups were comparable regarding age, gender and education. However, diabetes and hypertension were more frequent in the control group. The mean BPDAI total score was 51.39 ± 68.92 in BP patients and most of them used rituximab (41.7%). None of the participants had MS or Alzheimer MRI patterns. There was no difference between groups in terms of GCA and MTA scores. Furthermore, the frequency of partially empty sella did not differ significantly between BP patients and controls (p = 0.461); nevertheless, grade-3 Fazekas was significantly higher in BP patients compared to controls (25% vs. 0%, p = 0.019). Of note, one BP patient had an epidermoid cyst and another had moderate enlargement of three ventricles. Also, new infarcts were observed in two and old infarcts in four BP patients. Although the majority of abnormal brain MRI findings were more frequent in BP patients compared to controls, only grade-3 Fazekas was significantly higher and acute infarcts were exclusively observed in BP patients.

Progressive mucinous histiocytosis treated successfully with thalidomide: a rare case report.

Hereditary progressive mucinous histiocytosis (HPMH) is an extremely rare progressive non-Langerhans cell histiocytic disorder presenting with only cutaneous manifestations. Patients typically present with multiple asymptomatic dome-shaped erythematous papules, usually involving the face and upper extremities. Twenty-six cases have been reported worldwide, with no spontaneous regression. Treatment with thalidomide stopped the progression of the disease in two cases. We report a case of progressive mucinous histiocytosis in a 31-year-old female patient with a history of tuberculosis who presented papular lesions on the face that later extended to the hands. She was treated with isoniazid for tuberculosis and isotretinoin for the skin lesions; the improvement was minimal during the next two months, with new lesions appearing on both hands. Thalidomide stopped the progression of the disease. The cause and pathogenesis of HPMH are undetermined. The pathogenesis of HPMH may be similar to that of lysosomal storage disease, considering the intra-cytoplasmic phospholipid deposition in both diseases, in addition to the likelihood of a role of macrophages in triggering the disease. In our patient, tuberculosis may have contributed.

Novel PGM3 mutation in two siblings with combined immunodeficiency and childhood bullous pemphigoid: a case report and review of the literature.

BACKGROUND: Bullous pemphigoid is the most common autoimmune subepidermal blistering disorder with a low incidence in childhood. Combined immunodeficiencies (CIDs) are a group of monogenic inborn errors of immunity (IEIs) characterized by T- and B-cell dysfunction leading to recurrent infections, lymphoproliferation, predisposition to malignancy, and autoimmunity. Here, we report two Afghan siblings with a diagnosis of CID and extremely rare manifestation of diffuse bullous pemphigoid skin lesions. CASE PRESENTATION: The older sibling (patient 1) was a 32-month-old male with facial dysmorphism, protracted diarrhea, failure to thrive, recurrent oral candidiasis, recurrent otitis media with tympanic membrane perforation, who had been previously diagnosed with CID. While he was under treatment with intravenous immunoglobulin (IVIg), he developed extensive blistering lesions, which were diagnosed as childhood bullous pemphigoid. Methylprednisolone and azathioprine were added to the regimen, which resulted in a remarkable improvement of the skin lesions and also the feeding condition. However,2 weeks later, he was re-admitted to the intensive care unit (ICU) and eventually died due to fulminant sepsis. Later, his 12-month-old sister (patient 2) with similar facial dysmorphism and a history of developmental delay, food allergy, recurrent oral candidiasis, and respiratory tract infections also developed blistering skin lesions. She was under treatment for occasional eczematous lesions, and had been receiving IVIg for 3 months due to low levels of immunoglobulins. Further immunologic workup showed an underlying CID and thus treatment with IVIg continued, gradually improving her clinical condition. The genetic study of both siblings revealed a novel homozygous mutation in exon 7 of the PGM3 gene, c.845 T > C (p.Val282Ala). CONCLUSIONS: Dermatologic disorders may be the presenting sign in patients with CID and mutated PGM3. This case report further extends the spectrum of skin manifestations that could be observed in PGM3 deficiency and emphasizes the importance of considering CIDs during the assessment of skin disorders, particularly if they are extensive, recurrent, refractory to treatment, and/or associated with other signs of IEIs.

Leukocytoclastic vasculitis presenting clinically as bullous pyoderma gangrenosum following leucovorin, fluorouracil and oxaliplatin chemotherapy: a rare case report and literature review.

There are no published cases about bullous pyoderma gangrenosum induced by leucovorin, fluorouracil and oxaliplatin (FOLFOX) chemotherapy. With the increasing incidence of gastric and colorectal cancers and the increased usage of targeted therapies, some cutaneous adverse effects may become common. An 84-year-old male presented to our clinic with multiple ulcerative plaques covered with hemorrhagic crusts on both extremities after several FOLFOX chemotherapy sessions for gastric cancer and liver metastasis. Two weeks later, multiple bullae also appeared, especially on the acral areas. The histopathology examination was compatible with acute leukocytoclastic vasculitis. The FOLFOX chemotherapy regimen is increasingly administered considering the rising incidence of gastrointestinal cancers. Hence, our understanding of its possible side effects and complications must be heightened.

Efficacy and safety of chitosan-based bio-compatible dressing versus nanosilver (ActicoatTM ) dressing in treatment of recalcitrant diabetic wounds: A randomized clinical trial.

Chitosan has a biocompatible, biodegradable, and nontoxic nature. The effectiveness of Nano-chitosan films in the field of wound healing has been confirmed previously. The aim of this study was to compare the clinical efficacy and safety of two dressings (chitosan and nanosilver dressings) in the treatment of refractory diabetic wounds. A total of 25 eligible patients with chronic diabetic wound were included and randomly assigned to receive chitosan (13 patients) or nanosilver (12 cases) dressing. The dressings were applied on the wounds based on their protocols and patients were visited and examined by an experienced dermatologist every week. The clinical assessments and healing rates were recorded using diabetic-foot-infection (DFI) score at the 2nd, 4th, and 6th weeks during treatment. The study endpoint, safety and tolerability profile were also documented. The patterns of change in total 10-item-DFI wound scores did not differ significantly over time between the two groups. In both groups, the total 10-item-DFI wound score reduced continuously through the course of study. The mean percentage reduction of this score from baseline was 78.1% and 74.1% in the chitosan and nanosilver dressing groups, respectively. Both dressings were well tolerated and there were no adverse events. The relatively small sample size in both groups was the main limitation of the study. Our findings confirmed that chitosan may be safely and effectively used for the treatment of diabetic wounds just like the nanosilver (ActicoatTM ) dressing. Further studies are recommended with more volunteers and a longer follow-up period.

COVID-19 Pandemic Impact on Severe Alopecia Areata Patients.

Introduction: The pandemic of COVID-19 has several implications for patients with chronic stress-sensitive diseases such as alopecia areata (AA). On the other hand, the vulnerability of AA patients using immunosuppressives to a more severe infection is in the shadow of ambiguity. This teledermatology study aimed to evaluate the course and outcome of AA in patients during this challenging period. Methods: Patients with AA who had previously received systemic therapy included in this study. Information about demographic data, AA history, characteristics, and treatments, hair loss progression, Corona Disease Anxiety Scale (CDAS), adherence to protective measures against the COVID-19, possible infection, and its features obtained via a telephone call. Results: A total of 57 patients participated. The majority (84.2%) of the participants had mild anxiety assessed by CDAS. Two patients (3.5%) had got infected with COVID-19. Twenty-one (36.8%) participants experienced hair loss progression. Hair loss progression correlated with drug dose reduction (OR: 46.09, 95% CI 5.48-387.14, p < 0.001) although it did not influence by the level of anxiety evaluated by the CDAS (p > 0.05). Conclusion: The anxiety perceived by severe AA patients about COVID-19 is mild; however, many experience hair loss progressions owing to their drug dose reduction.

Evaluation of combination use of phenytoin cream 1% and fractional CO2 laser in treatment of stable nonsegmental vitiligo: A pilot study.

Vitiligo is an autoimmune disorder of melanocyte characterized by macular and depigmented patches. There are several treatment modalities for this disease, including the use of corticosteroids, calcineurin inhibitors, vitamin D analogous and topical phenytoin. Combination therapy utilizing fractional CO2 laser with different topical agents has been used to enhance treatment response with promising results. In this study, we aimed to evaluate the effect of fractional CO2 laser in combination with topical phenytoin. In this study, 25 patients (11 females and 14 males) with age of 18-59 (mean age of 31.12) with nonsegmental stable vitiligo were recruited with insufficient response to at least 1-year treatment with a monotherapy using topical corticosteroids, calcineurin inhibitors, and/or NB-UVB phototherapy. Patients were treated with a combination of fractional CO2 laser (10,600 nm, pulse energy 30-50 mJ, MIXEL, South Korea, Rating: 220VAC, 3A, 50/60 Hz) with monthly intervals for six sessions and application of phenytoin 1% cream twice daily. Photography was done before and after treatment with Wood's lamp. The severity of disease using VASI score was calculated and compared before and after treatment. The mean VASI score before treatment was 0.55, and sixth month after treatment increased to 1.97 (p-value < 0.001). Patients were divided into three groups based on the vitiligo subtype: acral, upper extremities, and trunk. VASI score was measured in each group: VASI score before and after treatment was 0.50 and 1.48 in acral areas, 0.45 and 2.04 in upper extremities and 0.79 and 3.39 in trunk, respectively. This study revealed that combination therapy with phenytoin and fractional CO2 laser is effective in treatment of vitiligo not only in the upper extremities and trunk, but also interestingly in the acral areas.

Ichthyosis follicularis syndromes in patients with mutations in GJB2.

Ichthyosis follicularis (IF) manifests as generalized spiny follicular projections found in syndromic diseases secondary to SREBF1 and MBTPS2 mutations. We sought the genetic cause of IF in two distinct families from a cohort of 180 patients with ichthyosis. In Family 1, the proband (Patient 1) presented with IF, bilateral sensorineural hearing loss and punctate palmoplantar keratoderma. Using DNA from peripheral blood lymphocytes, two compound heterozygous mutations, c.526A>G and c.35delG, were discovered in GJB2. In Family 2, the proband (Patient 2) presented with a previously unreported IF phenotype in the context of keratitis-ichthyosis-deafness syndrome, and whole-exome sequencing found a de novo heterozygous mutation, c.148G>A in GJB2. Histopathology was consistent with porokeratotic eccrine ostial and dermal duct naevus (PEODDN) and IF in Patients 1 and 2, respectively. Our findings add to the clinical and histopathological spectrum of IF and emphasize the association of PEODDN-like entities with GJB2 variants.

Losartan treatment improves recessive dystrophic epidermolysis bullosa: A case series.

Recessive dystrophic epidermolysis bullosa (RDEB) manifests with blistering and erosions of the skin and mucous membranes due to mutations in COL7A1. The repetitive wound healing processes lead to extensive cutaneous scarring. The scarring is driven by inflammatory processes, particularly the TGF-ß signaling pathways, resulting in excess synthesis and deposition of the extracellular matrix, especially collagen. There is currently no effective or specific treatment for RDEB. Losartan, an angiotensin II type 1 receptor antagonist, is an inhibitor of TGF-ß activity. Previous preclinical studies with hypomorphic Col7a1 mice recapitulating features of RDEB have suggested that losartan may improve the clinical features of RDEB. In this case series, we assessed the effects of losartan on the clinical and histopathologic features in seven patients with RDEB; three females and four males; aged 18.1 ± 9.1 years. The diagnosis was based on characteristic clinical features and the presence of biallelic loss-of-function mutations in COL7A1. Daily oral administration of losartan (0.7 mg/kg) for six weeks resulted in subjective improvement of the clinical features, as judged by the treating physicians and the patients, and the severity of the disease objectively improved based on Birmingham Epidermolysis Bullosa Severity (BEBS) score (30.1 ± 12.8 versus 23.3 ± 10.4, before and after treatment, p = 0.018), accompanied by improvement of quality of life, as determined by the EB-QoL questionnaire (24.0 ± 8.1 versus 17.7 ± 5.5, p = 0.018). Histopathology of the selected lesions revealed after treatment increased number of mast cells, and enhanced microvasculature in the mid and lower dermis. The width of collagen bundles in dermis was suggested to be decreased in four samples and changed from dense to loose in appearance. In summary, this case series reports beneficial effects of losartan on RDEB as a potentially novel treatment.

Low serum levels of zinc and 25-hydroxyvitmain D as potential risk factors for COVID-19 susceptibility: a pilot case-control study.

BACKGROUND AND AIMS: This study aimed to evaluate serum 25-hydroxyvitmain D and zinc levels in coronavirus disease 2019 (COVID-19) patients in comparison to healthy subjects. METHODS: This was a single-center case-control study performed from March 20, 2020, to January 20, 2021, in Tehran, Iran. All patients diagnosed with COVID-19 based on a positive nasopharyngeal swab polymerase chain reaction (PCR) test were included in the case group. Controls were selected from patients referred for routine checkups who had a negative COVID-19 PCR test. Age, sex, marital and educational status, comorbidities, and serum 25-hydroxyvitmain D and zinc levels of patients were recorded. RESULTS: Ninety patients in the case group and 95 subjects in the control group who were sex and age-matched were studied. 25-hydroxyvitmain D levels higher than 20 ng/ml were observed in 58 (64%) cases and 72 (76%) controls (P = 0.09). The median 25-hydroxyvitmain D level in the case group was significantly lower than controls (26 (interquartile range [IQR] = 24) ng/ml vs. 38 (IQR = 22) ng/ml, respectively, P < 0.01). The median zinc level in the case group was 56 (IQR = 23) mcg/dL, while it was 110 (IQR = 27) mcg/dL among the controls (P < 0.01). There was no significant difference in the level of 25-hydroxyvitmain D and zinc between cases with and without comorbidities (P > 0.05). Susceptibility to SARS-CoV-2 infection could be predicted by serum 25-hydroxyvitmain D levels below 25.2 ng/ml (81% sensitivity; 48% specificity) or zinc levels below 86.3 mcg/dL (93% sensitivity; 92% specificity). CONCLUSIONS: Low serum zinc and 25-hydroxyvitmain D levels appear to be risk factors for COVID-19 affliction; thus, the treatment of individuals with such deficiencies is recommended.