Intranuclear rodlets and associated true intranuclear bodies in normal cultured human dermal papilla cells.

The dermal papilla is believed to exert controlling influences on hair growth. This report documents, for the first time, the occurrence of intranuclear rodlets in normal cultured human dermal papilla cells. Intranuclear rodlets have been observed predominantly in normal neurons, neural neoplasms, and paraneuromas. Whereas intranuclear rodlets and complex intranuclear bodies have not been identified in dermal papilla cells in vivo, they were observed, by light microscopy and transmission electron microscopy, in primary and subsequent passaged cultures in all 10 individuals examined. Intranuclear rodlets and bodies were not found, however, in parallel cultures of scalp dermal fibroblasts from the same individuals. Rodlet ultrastructure in cultured dermal papilla cells exhibited many features in common with previous reports on rodlets in neuronal and paraneuronal cells. Features that differentiated the rodlets in this study, however, included: doublet/triplet rodlets in the same nucleus; rodlets or crystalline filament bundles within complex nuclear inclusions; close relationship with the nuclear membrane, and their frequent intimate association with intranuclear bodies; and nucleoli and fine chromatin-distinct fibrillar material. Although the function of these true intranuclear inclusions in dermal papilla cells is unknown, it is noteworthy that they were present in these highly metabolically active fibroblasts while absent in comparatively less active dermal fibroblasts, and may indeed be a marker for this fibroblast cell type.

Antibodies to hair follicles in alopecia areata.

Although alopecia areata is suspected to be an autoimmune disease, no direct evidence of an altered immune response to components of the hair follicle has been reported. We studied whether antibodies to normal human anagen scalp hair follicles are present in individuals with alopecia areata. Thirty-nine alopecia areata sera and 27 control sera were tested by Western immunoblotting for antibodies to 6 M urea-extractable proteins of normal anagen scalp hair follicles. At serum diluted 1:80, all alopecia areata subjects (100%), but only 44% of control individuals, had antibodies directed to one or more antigens of approximately 57, 52, 50, 47, or 44 kD. The incidence of antibodies to individual hair follicle antigens in alopecia areata was up to seven times more frequent than in control sera and their level up to 13 times greater and was statistically significant for all five antigens. Tissue specificity analysis indicated that these antigens were selectively expressed in hair follicles. These findings indicate that individuals with alopecia areata have abnormal antibodies directed to hair follicle antigens, and support the hypothesis that alopecia areata is an autoimmune disease.

Ultrastructural observations on the hair bulb melanocytes and melanosomes in acute alopecia areata.

It is well recognized that alopecia areata (Aa) may preferentially affect pigmented hair and may spare white hair, and that regrowing hair in the disease is often initially white. In addition, there is an association with vitiligo and ocular depigmentation. To date, the pathomechanisms of the melanocyte effects are unclear. We have studied 10 patients with untreated acute alopecia areata, and three normal patients without hair loss. Morphologic changes, studied by conventional light and electron microscopy, in the cytoplasm of affected melanocytes often predated nuclear hyperchromatism. Increased numbers of bizarre melanosomes were found in affected melanocytes compared with normal ones; such melanosomes had incomplete or "aborted" melanization, resulting in poor pigment deposition, and were disrupted, enlarged and rounded, with loss of normal ellipsoidal shape. An unusual outer root sheath (ORS) distribution of hair bulb melanocytes was seen. Other atypical melanosome effects included marked pigment displacement into peribulbar and DP melanophages. In the DP clumped melanin granules formed giant spherical complexes without discernible limiting membranes, which were sometimes associated with lymphocytes. These morphologic changes indicate an active involvement of hair bulb melanocytes in alopecia areata.

Alopecia areata treated with tropical minoxidil.

Two cases of long-standing alopecia totalis treated with topical minoxidil are described. The mechanism of minoxidil hypertrichosis is discussed.

Family exhibiting cerebellar-like ataxia, photosensitivity and shortness of stature - a new inborn error of tryptophan metabolism.

Two cases in a brother and sister of a previously undescribed hereditary syndrome are reported. The features, which include shortness of stature, photosensitivity and cerebellar-like ataxia, are attributed to a new inborn error of tryptophan metabolism.

Topical minoxidil in the treatment of alopecia areata.

A modified double blind crossover study was performed to assess the effect of 1% topical minoxidil as compared with placebo in 30 patients with alopecia areata and alopecia totalis. The active preparation produced a highly significant incidence of hair regrowth. A cosmetically acceptable response was noted in 16 patients. No side effects were seen. The study confirmed that topical minoxidil will induce new hair growth in alopecia areata but that it is less likely to do so in more severe and extensive disease. Furthermore, patients with alopecia universalis and totalis may not respond at all. Nevertheless, as compared with other drugs minoxidil applied topically is relatively non-toxic, is easy to use, and has no systemic or local side effects.

Cell degeneration in alopecia areata. An ultrastructural study.

The morphology and prevalence of different forms of cell degeneration in hair follicles in acute alopecia areata were investigated. In addition to apoptosis and necrosis, a third morphological pattern of cell degeneration, dark-cell transformation, was evident. Fifteen patients with untreated acute alopecia areata and three normal adults without hair loss were studied. Electron microscopy revealed that although apoptosis of outer root sheath keratinocytes produces normal hair follicle involution (catagen), increased levels of apoptosis, necrosis, and dark-cell formation appear to be related to the pathology of alopecia areata. Although cell degeneration was generally restricted to keratinocytes of the lower follicle, melanocytes, Langerhans' and dermal papilla cells were also affected. Keratinocytic degeneration may affect layers of matrix cells in alopecia areata, unlike the apoptosis of scattered outer root sheath cells in normal catagen. The extent of cell death suggests a pathological rather than a physiological event in alopecia areata.