David A. Fenton

Expanding the spectrum of frontal fibrosing alopecia: A unifying concept

BACKGROUND In frontal fibrosing alopecia (FFA), scalp alopecia dominates the clinical picture. However, eyebrow loss and hair loss in other body sites may also occur; this has been documented clinically, but rarely histopathologically. We describe the clinicopathological findings of 13 cases of FFA, with histopathologic data from the scalp, eyebrow, and body hair. METHODS Thirteen patients with a diagnosis of FFA, seen between 2006 and 2008, were included. Scalp biopsies were performed in all patients for histology and direct immunofluorescence (DIF). Biopsy specimens for histology were taken from the eyebrow in 6 patients and from the upper limb in 5 patients. RESULTS All 13 patients were female, 11 of whom were postmenopausal. The median age at onset of alopecia was 57 years. Clinical examination revealed a band of frontal hairline recession in all patients. Eyebrow loss was present clinically in all patients, with loss of body hair in 10 of 13. Histopathologic examination of the scalp, eyebrow, and upper limb skin biopsy specimens showed similar features, including a marked reduction in the number of hair follicles and a perifollicular lymphoid cell infiltrate with perifollicular fibrosis. Direct immunofluorescence was negative in all cases. LIMITATIONS Not all patients consented to biopsies of the eyebrows or upper limbs. CONCLUSION Eyebrow and peripheral body hair loss is not uncommon in FFA-a finding that is likely underreported. We have demonstrated that alopecia of the upper limbs in FFA is indeed common and, histopathologically, shows features of lichen planopilaris and scarring, similar to findings in the scalp and eyebrows. Consequently, the process of lichen planopilaris with scarring alopecia is generalized rather than localized only to the frontal scalp and eyebrows.

Lymphatic function in the yellow nail syndrome

Summary Peripheral oedema is commonly seen in the yellow nail syndrome (YNS). Contrast lymphangiography has shown abnormal collecting lymphatics in some patients with YNS. In this study, lymphatic function in the upper and lower limhs of 1 7 patients with YNS, in normal controls, and in patients with established classical lymphoedema, has been assessed using quantitative lymphoscintigraphy. Nine subjects with YNS had swelling of the legs and two had features typical of lymphoedema. The lymphatic drainage was significantly reduced in the legs of patients with YNS but not lo the level seen in lymphoedema. Lymphatic function was also reduced in the arms in patients with YNS. Venous insufficiency did not contribute to the leg oedema.

Trichohyalin is a potential major autoantigen in human alopecia areata.

Several lines of evidence support an autoimmune basis for alopecia areata (AA), a common putative autoimmune hair loss disorder. However, definitive support is lacking largely because the identity of hair follicle (HF) autoantigen(s) involved in its pathogenesis remains unknown. Here, we isolated AA-reactive HF-specific antigens from normal human scalp anagen HF extracts by immunoprecipitation using serum antibodies from 10 AA patients. Samples were analyzed by LC-MALDI-TOF/TOF mass spectrometry, which indicated strong reactivity to the hair growth phase-specific structural protein trichohyalin in all AA sera. Keratin 16 (K16) was also identified as another potential AA-relevant target HF antigen. Double immunofluorescence studies using AA (and control sera) together with a monoclonal antibody to trichohyalin revealed that AA sera contained immunoreactivity that colocalized with trichohyalin in the growth phase-specific inner root sheath of HF. Furthermore, a partial colocalization of AA serum reactivity with anti-K16 antibody was observed in the outer root sheath of the HF. In summary, this study supports the involvement of an immune response to anagen-specific HFs antigens in AA and specifically suggests that an immune response to trichohyalin and K16 may have a role in the pathogenesis of the enigmatic disorder.

Darier's disease: an immunohistochemical study using monoclonal antibodies to human cytokeratins

The pathogenesis of Dariers disease was investigated by immunohistochemical staining of skin biopsies from involved and uninvolved skin in 14 patients, using monoclonal antibodies specific for keratins expressed in simple epithelia, stratified squamous epithelia and during skin specific differentiation as well as keratins expressed in mucosa and some benign epidermal hyperproliferative states.

Low-dose dapsone in the treatment of subacute cutaneous lupus erythematosus.

Several therapies have been suggested for subacute cutaneous lupus erythematosus (SCLE) including topical and systemic corticosteroids, antimalarials, immunosuppressives, thalidomide and clofazimine. A recent paper reported a dramatic response to dapsone (McCormac, Elgart & Turner, 1984). We describe a patient with a 3-year history of SCLE who was resistant to standard treeatment, but who cleared completely with low-dose dapsone therapy.

Effect of retinoids on follicular cells

It has been demonstrated that topical application of all-trans retinoic acid and other retinoids can alter the hair-growth cycle in the C3H mouse model. The anagen phase is prolonged and the telogen phase is shortened. This effect is similar to the effect of minoxidil on the hair-cycle dynamics in this animal model. The levels of cellular retinoic acid binding protein measured by radioreceptor assay in whole skin of C3H mice were higher during anagen and lower during telogen. Topical application of certain retinoids caused elevated levels of cellular retinoic acid-binding protein (cRABP) in the whole skin homogenates during both phases of the cycle. Of the retinoids tested, those most effective in altering the levels of cRABP in the skin of the mice were also capable of significantly altering the hair-cycle dynamics. There appeared to be a relationship between the ability of retinoid to increase cRABP, increase 3H-thymidine incorporation, and alter the dynamics of the hair cycle. Only cRABP-II is detectable in human cultured dermal fibroblasts and dermal papilla cells. Dermal fibroblasts showed higher amounts of cRABP-II as compared to dermal papilla cells. The difference in cRABP-II expression might explain a distinct response to RA by these two cell populations. Whether the difference in expression of cRABP-II might be of physiologic importance remains to be determined. Treatment of human dermal papilla cells in culture with retinoic acid does not appear to affect proliferation, at least at the doses tested.

Ultrastructural study of exclamation-mark hair shafts in alopecia areata.

The prime diagnostic feature of acute alopecia areata is the presence of exclamation mark hairs. These characteristic hairs fracture at their distal end and taper proximally towards the scalp, giving them the appearance of an exclamation mark. Hair morphology was studied in 8 patients with untreated acute alopecia areata and 3 normal adults without hair loss. Light microscopy, transmission and scanning electron microscopy revealed distinct structural differences in the distal end of hairs compared with the remainder of their length and with normal hair shafts. Transverse sections of hairs just below the frayed brush‐like tip often displayed asymmetrical cortex disintegration. One side was compact and homogeneous while the other was deeply fissured and/or broken up into discrete heterogeneous‐staining fragments of cortical, stratum corneum and cuticular components in addition to apparently degenerate cortex. Many exclamation mark hair tips lacked cuticle and had irregular profiles. Melanin was found in cortical and medullary fragments at the tip, although it was absent in the more degenerate forms of cortex. More proximal sections of these pathognomic telogen hairs revealed nearly normal hair shaft ultrastructure.

Invasive nasal sarcoidosis treated with methotrexate

A patient with invasive sarcoidosis is described in whom upper respiratory tract symptoms were the presenting complaint of this severely disfiguring disease. Methotrexate was used as an effective alternative to high dose systemic steroids which were contraindicated in this case.

Frontal fibrosing alopecia and lupus overlap in a man: guilt by association?

Frontal fibrosing alopecia (FFA) is a scarring alopecia, now an accepted subset variant of lichen planopilaris (LPP). Its occurrence in males is rare, with only nine cases reported to date. We describe a case of FFA in a male in association with lupus erythematosus. Multiple biopsies from the scalp, eyebrow and arm showed features consistent with LPP, in keeping with the clinical presentation of FFA. Direct immunofluorescence studies showed a positive lupus band test. Further serological investigation confirmed the presence of antinuclear, anticardiolipin and lupus anticoagulant antibodies. Whilst the findings of lupus erythematosus may be coincidental or a forme fruste of the disease occurring in association with FFA, it is feasible that lupus and LPP may occur as an overlap syndrome. This case underscores the importance of multiple biopsies and the role of direct immunofluorescence in disclosing more than one pathology in the follow-up of patients with scarring alopecia.

Clinical patterns of lichen planopilaris in patients with vulval lichen planus

dilator was used several times a day. The chronic back pain was no longer noticeable. A successful relocation of the sigmoid colon was performed without any complication 13 weeks after the protective stoma had been made. During follow-up visits the patient presented shrinking nonirritated wounds. Defecation was normal, manometry was positive and continence normal. Moreover she reported that she had gained weight and had reached her original body weight again. Anorectal necrosis after paracetamol abuse is rare, only a few cases have been described before. The pathological mechanism leading to anorectal necrosis after paracetamol abuse is still unknown. Paracetamol is widely used as an antipyretic and analgesic drug, however it also has vasoconstrictive properties. Therefore it is applied in neonatology for closure of the ductus arteriosus. It is highly probable that the vasoconstrictive properties are responsible for the perianal necrosis in our patient. In the present case, the correct diagnosis at an earlier time point could have avoided the invasive surgical treatment and shortened the duration of the patient’s disease. This case underlines the importance of a detailed medical history and the clinical experience of the treating physician in reaching the correct diagnosis.