Riehl’s melanosis is a pigmented lesion of the skin that is mainly brown or blue-gray in color and is associated with a variety of factors. It was first reported by Riehl in 1917 during World War I. As the war ended, the number of cases declined significantly, hence the name “war melanosis”. This paper reviews the etiology, pathogenesis, and clinical manifestations of Riehl’s melanosis and describes the current state of knowledge about Riehl’s melanosis.
1. Etiology
The exact etiology of Reye’s melanosis is still unclear. Early on, it was found that the disease disappeared with the end of World War I, and a new epidemic was observed during World War II, which seemed to be related to the living conditions of people during the war, and Riehl himself believed that it was related to certain foods used in the war. Recent research observations suggest that it may be related to the following factors.
(1) Long-term use of cosmetics containing coal tar-based dyes: Riehl’s melanosis of the face is particularly common in Japan. a study by Tetsuro Sugm showed that a patch test using four allergens commonly contained in cosmetics on patients with clinical manifestations similar to Riehl’s melanosis resulted in the highest positive rate in the coal tar group (81.6%), and in the coal tar group, the bright precursor red R The highest positive rate (57.9%) was found in the coal tar group. In the coal tar group, the highest positive rate (57.9%) was found for Brilliant Red R. Before 1976, Brilliant Red R was widely used in rouge and lipstick. With the withdrawal of cosmetics containing Leucocyanidin R from the Japanese market, the positive rate of patch test for cosmetics containing the dye decreased significantly (from 80% in 1975 to 31.6% in 1976), and patients who were sensitive to Leucocyanidin R gradually lost their pigmentation after daily use of cosmetics without Leucocyanidin R, and some of them were even completely cured. This shows that Leucocyanidin Red R may have a certain connection with Rell’s melanosis.
(2) Malnutrition: Some patients have lower than normal values of vitamin A, vitamin C, vitamin D, niacin, etc.
(3) Prolonged sun exposure: hyperpigmentation in Reye’s melanosis occurs mostly on the forehead, zygomatic region, behind the ears, on the sides of the neck, and other sun-exposed areas. In some of the reported cases, the patients had a history of prolonged exposure to sunlight. It is presumed that the occurrence of Reye’s melanosis may be related to sun exposure, but it has also been pointed out that only 29.8% of patients who used coal tar-containing cosmetics had a positive light spot patch test, and the connection between sun exposure and Reye’s melanosis needs to be further studied.
(4) Other factors: Some scholars in China reported a case of Ryle’s melanosis complicated by tuberculosis after anti-tuberculosis treatment, the lung tuberculosis lesions were completely absorbed, and Ryle’s melanosis was also healed, so it is thought that tuberculosis may play a role in the development of the disease, but further research is needed. In addition, mental factors also seem to play a role in the development of the disease, and a case of depression due to the drowning death of his daughter and the subsequent development of Reye’s disease has been reported in China.
2.Pathogenesis
The exact pathogenesis of Reye’s melanosis remains unclear, and after 1940 it was generally believed that Reye’s melanosis was secondary to contact dermatitis. Several studies have also suggested that delayed hypersensitivity to cosmetics and fragrances is prevalent in Ryle’s melanosis, and therefore the concept of pigmented cosmetic dermatitis or pigmented contact dermatitis has been proposed, and the Japanese Most dermatologists consider these two concepts to be equivalent to Reye’s melanosis.
A light and electron microscopic study of Ryel’s disease revealed that in Ryel’s disease, on the one hand, the melanocytes of the epidermis are rich in pre-melanocytes, well-developed Golgi apparatus and granular endoplasmic reticulum; on the other hand, the gap between keratinocytes is wider than normal and the keratinocytes contain fewer melanocytes than normal. It seems that the transport of melanosomes from melanocytes to keratinocytes was disturbed, and melanosomes inevitably fell into the dermis.
As to what is the pathway of melanosomes into the dermis or how hyperpigmentation occurs, the following findings may partially explain. First, Mishima (1967) found that the Swan cells of unmyelinated nerve fibers in the dermis and epidermis were rich in melanosomes, thus suggesting that the nerve component may engulf the melanosome tensor filament-bridge granule complex, and that there are no pre-melanosomes or Langerhans granules, but are rich in engulfing vesicles and have some extracellular melanosomes immediately surrounding it. These findings suggest that this cell may be a macrophage, which may be able to engulf melanosomes and can carry them across the basement membrane to the dermis. The neural component may play a role in the pigment incontinence of Rell’s melanosis. On the other hand, a very odd type of multi-dendritic pigment cell was found in the epidermis, which contains neither
In terms of molecular biology, it has been demonstrated that the pigmentation produced by Phenyazonaphthol (PAN) as an allergen in the skin of brown guinea pigs is associated with a specific melanogenic factor produced in the allergic reaction. In terms of signal transduction, melanogenesis due to PAN allergy is mediated by activation of protein kinase C (PKC) in melanocytes by a soluble factor produced in the allergic response. This soluble factor is called PAN-induced melanogenic stimulating factor (PIMSF). The molecular weight of PIMSF was found to be about 7.9 kDa by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) technique, and it is similar to the growth related oncogene a (GROa) of the mouse. The two are parallel, thus suggesting that purified PIMSF may have a close association with the GRO family. It has been reported that GROa is expressed in cultured human keratin-forming cells and that its expression is enhanced after exposure to UVB or treatment with IL-1a. There is much evidence that the initial phase of GRO production by keratinocytes is accompanied by a cascade of IL-1a activation, including keratinocyte receptor 1. Therefore, the production of GRO in the epidermis caused by allergy may be triggered by IL-1a.
3. Clinical manifestations
Rheumatoid melanosis occurs mostly in middle-aged women and can also involve men. The characteristic skin lesions show brown to black reticular pigmentation on the face and neck. It occurs mostly on the temporal, cheek,, nose and both sides of the neck, and the perioral and mandibular areas are often not involved and do not involve the mucous membranes.
Clinically, it can be divided into three phases.
Inflammatory phase: mild flushing and swelling of the affected area, a little chaff-like flaking, itching and burning sensation may be present.
Pigmentation phase: As the inflammation fades, pigmentation appears. Initially, it is often confined to the peri-pore area in the form of a dot, but later it may fuse into a patch, and some patients may enter the atrophic phase.
Atrophic phase: Mild depressed atrophy of the skin consistent with the site of hyperpigmentation appears. Accompanying symptoms may include dizziness, fatigue, tinnitus, hearing loss, loss of appetite and other non-specific symptoms.
4.Pathological manifestations
Obvious pigment incontinence and phagocytosis of melanocytes in the dermal papillary layer. In the early stage, there is liquefied degeneration of the basal layer of the epidermis, and in the late stage, the epidermis tends to be normal and the inflammatory infiltration disappears.
5.Treatment
There is no specific treatment for this disease. The primary principle of treatment is to remove the cause of the disease and symptomatic treatment.
(1) General treatment
The main treatment consists of removing the suspected contact and avoiding sun exposure. Use a strong sunscreen (SPF>30, PA++).
(2) Drug treatment
Oral vitamin A, vitamin C. Oral corticosteroids and non-steroidal anti-inflammatory drugs can be used to control inflammation during the inflammation period. In the period of hyperpigmentation, external depigmentation agents such as 3% hydrogen peroxide 1.5%-4% hydroquinone cream can be used, and external corticosteroids can also be used.
(3) Traditional Chinese medicine treatment
This disease belongs to the category of “sallow spots” in Chinese medicine, which is mostly caused by dampness trapping the spleen and earth and liver and kidney deficiency. The treatment mostly takes the form of strengthening the spleen and benefiting the qi, and harmonizing the yin and yang. According to the literature, many prescriptions have been reported to be effective in the treatment of this disease. For example, Tonifying Liver and Benefiting Qi Tang, Blood Mansion and Stasis Removal Tang, and Awakening Spleen and Haze Tang. Among them, one author reported 110 cases of Ryle’s melanosis treated with Awakening Spleen and Haze Tang, 80 cases were cured, 23 cases improved, and 7 cases were ineffective, with a total efficiency of 93%. Some authors also reported that acupuncture was used to treat this disease with good results.
(4) Intense pulsed light/laser treatment
Through the principle of selective photothermal action, intense pulsed light/laser can selectively destroy melanin vesicles, causing melanin masses to disintegrate and be discharged from the body with skin flakes or with lymphatic circulation. It usually takes several treatments (10-20 times) to achieve significant results or even clinical cure.
Currently, we recommend the following treatment methods: removing the cause of the disease, such as relieving anxiety, avoiding smelly environments, and stopping the use of suspected drugs.
I. Intravenous drip
1.Tranexamic acid 1g/100ml, 1 hour slow drip (if the drip speed is too fast, it may cause headache). Avoid menstrual period (otherwise it may cause low menstrual flow), avoid fasting, occasional gastrointestinal side effects.
2.5％ glucose 250ml+glutathione 1.2g+vitamin C2.5.
After 2 weeks, it will be reduced to once a week, and 3 months will be a course of treatment, totaling 25 times. 3 months later, the next course of treatment can be started as appropriate.
Oral medication (if it is inconvenient to take the medication orally, it can be used instead)
1.Tranexamic acid 500mg (1 tablet), 2 times a day orally.
2.Glutathione 3 tablets, 2 times a day orally.
3.VC 1 capsule each time, three times a day.
4.VE 1 capsule each time, 2 times a day.
5.If the rash is red and itchy, take Acomplia (etoricoxib) orally, 1 tablet every night. Bevan (cetirizine hydrochloride), 1 tablet per night.
Third, strong pulse light treatment: 1 time a month, about 20 times in total. Q1064 can be used alternately, 1 time in 2 weeks.
IV. Topical medication.
Morning: glutathione gel/transaminic acid extract/leucovorin Vc + whitening gel + sunscreen.
Evening: Glutathione gel/Tranexamic acid extract/L-alpha Vc + whitening gel + hydroquinone cream.
V. Regular monitoring (once a month): blood routine, liver function, coagulation three.
After about 1-2 years of treatment, the vast majority of patients can get good improvement.
Although not a common or frequent disease in dermatology, Rheumatoid arthritis can be seen from time to time in clinical practice and can cause great psychological stress to the extent that it affects the daily life and social activities of patients. However, the specific etiology and pathogenesis of the disease have not been studied in depth, and there is no good treatment method. Therefore, further research is needed to find more appropriate treatment methods and tools to relieve patients’ suffering.